Synthesis of P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis

FULL PAPER

DOI: 10.1002/ejoc.201500767

Synthesis of P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

and Their Application in Asymmetric Catalysis

Christian Schmitz,^[a]Walter Leitner,*^[a]and Giancarlo Franciò*^[a]

Keywords: Asymmetric catalysis / Ligand design / P ligands / P-chirality / Betti base

A series of P-stereogenic monodentate phosphoramidite

as the interplay between the P-chirality and the stereocen-

(PNO₂) and phosphorodiamidite (PN₂O) ligands based on ters in the backbone were investigated. Enantioselectivities

chiral Betti bases has been prepared by modular synthetic

procedures. The chirality at the phosphorus can be controlled

to a large extent by the synthetic route, leading to stereo-

of up to 85 and 83% ee were obtained in the Rh-catalyzed

hydrogenation of dimethyl itaconate and in the Pd-catalyzed

allylic amination of (rac)-(E)-1,3-diphenylallyl acetate with

selective access to single P-epimers. The absolute configura- benzylamine, respectively. In the Ni-catalyzed hydrovinyla-

tion of the P-atom was assigned by X-ray diffraction analysis.

The new ligands were evaluated in asymmetric catalysis and

the influence of the exocyclic amine or alcohol moiety as well

tion of styrene, ee values of up to 68%, excellent chemo-

selectivities, and high activities (TOF_avup to 3000 h^–1) were

achieved.

cation in transition-metal-catalyzed asymmetric transfor-

mations.^[1,8]Most of the monodentate ligands containing

phosphorus–heteroatom bonds can be synthesized through

simple condensation reactions and in high yields from a

variety of chiral precursors, for example diols, amino

alcohols, or diamines, allowing for the creation of ligand

libraries to rapidly assess the optimum structure for a given

application.^[9]In particular, phosphoramidites have evolved

into a versatile class of ligands since the first reports by

Feringa and de Vries^[10]showed excellent enantioselectivit-

ies in a variety of transition-metal-catalyzed asymmetric

processes.^[11]Phosphoramidites provide broad opportuni-

ties for fine tuning of their donor–acceptor and steric prop-

erties by the incorporation of appropriate substituents at

the oxygen and nitrogen directly bound to the P-atom.^[12]

The large majority of reported phosphoramidites are com-

posed of a C₂-symmetric diol backbone (especially BINOL

or TADDOL) with a monoamine^[13]and, hence, do not

feature a P-stereogenic center. In general, the influence of

P-chirality on the catalytic behavior in ligands of type

PN_xO_y(x,y = 1,2) remains largely unexplored.

Introduction

The fruitful development of transition-metal-catalyzed

asymmetric transformations is closely related to the avail-

ability of an increasing number of chiral phosphorus li-

gands.^[1]The introduction of novel ligand structures has

contributed greatly to the evolution of this field, resulting

in a set of widely used tools for organic synthesis on both

a laboratory and an industrial scale.^[2]The overall chirality

of the ligand environment can result from stereogenic ele-

ments in the ligand backbone and/or at the donor atom

itself.

In 1961, Horner and co-workers isolated optically pure

trivalent phosphines^[3]and, some years later, Horner^[4]and

Knowles^[5]demonstrated the potential of such compounds

in asymmetric catalysis. Since these pioneering works, inter-

est in phosphorus ligands bearing chirality at the phos-

phorus atom has expanded greatly, and the development

of new efficient and stereoselective synthetic methodologies,

particularly those using phosphine borane chemistry, has

led to the availability of a large number of P-stereogenic

ligands.^[6]The choice of substituents at the P-atom allows

not only fine-tuning of the ligand features but also affects

the inversion barrier for the epimerization of the P-stereo-

genic center.^[7]

Apart from rare examples based on C₁-symmetric

BINOL derivatives and a monoamine (compounds 1–3;

Figure 1),^[14]P-stereogenic phosphoramidites have been

prepared by combining an alcohol and an amino alcohol

mostly derived from an amino acid or other natural prod-

uct.^[11c]

Chiral phosphorus compounds in which the donor atom

is surrounded by heteroatoms are finding increasing appli-

[a] Institut für Technische und Makromolekulare Chemie, RWTH

Aachen University

An early example of monodentate P-stereogenic phos-

phoramidites was reported by Pastor and Rodebaugh in

1988. Compounds 4 were synthesized from 2-(N-tert-but-

ylamino)ethanol as an amino alcohol building block, but

not tested in catalysis (Figure 2).^[15]Polosukhin et al. syn-

thesized monodentate phosphoramidites 5 from (S)-pro-

Worringer Weg 2, 52074 Aachen, Germany

E-mail: leitner@itmc.rwth-achen.de

francio@itmc.rwth-aachen.de

www.tc.rwth-aachen.de

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201500767.

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C. Schmitz, W. Leitner, G. Franciò

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amidites 17. These ligands were tested in the nickel-cata-

lyzed hydrovinylation of styrene without showing any cata-

lytic activity.^[24]In general, phosphorodiamidites derived

from amino alcohols were obtained as single diastereomers

and, hence, the effect in catalysis of the P-chirality could

not be addressed.

Figure 1. P-Stereogenic phosphoramidites derived from C₁-sym-

metric BINOL derivatives.^[14]

linol and several alcohols, leading to diastereomeric mix-

tures of P-epimers, which were not separated.^[16]Reetz and

Bondarev used (S)-α,α-diphenylprolinol and several

alcohols for the synthesis of phosphoramidites of type 6,

achivieng up to 95% ee in the Rh-catalyzed asymmetric

hydrogenation.^[17]A library of P-stereogenic phosphor-

amidites 7–11 possessing five- or six-membered phos-

phacycles and an exocyclic methoxy-substituent was syn-

thesized by Benetsky et al. and applied in the Pd-catalyzed

allylic substitution with up to 59% ee.^[12]However, previous

reports have either not investigated the impact of the P-

chirality in catalysis as single diastereomers or dia-

stereomeric mixtures have been employed as ligands for ca-

talysis.

Figure 3. P-Stereogenic phosphorodiamidites synthesized from

amino alcohols.^[21–24]

As shown in the examples mentioned above, most of the

reported P-stereogenic phosphoramidites and phosphorodi-

amidites were synthesized from amino alcohols derived

from natural α-amino acids. These provide, in most cases,

an inexpensive source of chirality but structural diversity is

limited and typically only one enantiomer is accessible from

the chiral pool.

An alternative source for chiral amino alcohols are the

Betti bases 18.^[25]Betti bases are easily prepared on

multigram scale from inexpensive starting materials by a

simple and straightforward condensation between 2-

naphthol, aryl aldehydes and ammonia or amines, which

finally provides a broad structural variety of amino

alcohols.^[26]When enantiopure chiral amines are used in the

synthesis of Betti bases, the reaction may proceed diastereo-

selectively, as was demonstrated for Betti base (R,R)-19

(Figure 4).^[27]

Figure 2. P-Stereogenic phosphoramidites synthesized from amino

alcohols containing five- or six-membered 1,3,2-oxaazaphos-

phacycles.^{[12,15,16,17]}

In a similar strategy, the combination of amino alcohols

with monoamines results in phosphorodiamidites (di-

amidophosphites) containing two P–N and one P–O bond,

which consequently possess a stereogenic P-atom.^[18,19]

Phosphorodiamidite ligands are underrepresented in the lit-

erature and their potential in catalysis has been assessed in

very few cases.^[20]For example, Bernard and Burgada

reported phosphorodiamidites 12 prepared from an

ephedrine derivative (Figure 3), but did not apply them in

asymmetric catalysis.^[21]Alexakis reported the synthesis and

application of P-stereogenic phosphorodiamidites 12–15

Figure 4. Betti bases containing one or two stereocenters.^[25–27]

Betti bases and their derivatives have been applied in or-

based on ephedrine and prolinol in Cu-catalyzed 1,4-ad- ganic synthesis and asymmetric catalysis (Figure 5). For ex-

dition and achieved enantioselectivities of more than 95% ample, they were used as chiral auxiliaries for enantiosepar-

ee.^[22]Bondarev and Goddard described P-stereogenic ation^[28]or as ligands (20–22) in the asymmetric addition of

phosphorodiamidites 16 derived from α,α-diphenylprolinol organozinc compounds to aldehydes.^[29]Furthermore, they

and their use in Rh-catalyzed asymmetric hydrogenation for have been used as chiral building blocks for phosphorus

which up to 91% ee was achieved.^[23]Recently, we reported ligands 23–24,^[30]providing good to high levels of stereo-

the synthesis of N-Phenyl-NOBIN derived phosphorodi- selectivity in asymmetric catalysis, and thus encourage fur-

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P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

ther investigations on the use of Betti base fragments as

constituent of novel chiral ligands for asymmetric cataly-

sis.^[26]In none of the previously reported examples have P-

stereogenic ligands been synthesized starting from a Betti

base.

Scheme 1. Synthesis of Betti base (R,R)-19 and (R,S)-19.

In contrast, the synthesis and isolation of (R,S)-19 has

not been previously reported; however, by simply per-

forming the reaction at room temperature, an almost 1:1

mixture of (R,R)-19 and (R,S)-19 could be obtained

(Scheme 1). Crystallization-induced asymmetric transfor-

mation^[32]towards the exclusive formation of (R,R)-19 was

not observed under these reaction conditions. From the

crude reaction mixture, pure (R,S)-19 was isolated by mul-

tiple crystallization in low yields of 13–16%.^[33]

Ligand Synthesis

Figure 5. Chiral Betti bases and Betti-base-derived phosphorus li-

gands that have been applied successfully in asymmetric cataly-

sis.^[29,30]

Like other phosphorus ligands containing P–O and P–

N bonds,^[11b]the envisaged P-stereogenic phosphoramidites

and phosphorodiamidites are, in principle, accessible by two

convergent synthetic routes starting from phosphorus tri-

chloride (Scheme 2).

Herein, we describe the synthesis of a series of new chiral

phosphoramidite and phosphorodiamidite ligands based on

Betti base 19 in a straightforward and modular synthetic

protocol. The ligands include a stereogenic P-donor, and

two different P-epimers are possible. The envisaged ligands

are, in general, accessible by two different synthetic routes,

which were compared and optimized for each ligand class.

The predominantly formed P-epimer can be controlled to a

large extent by the use of the appropriate synthetic route,

allowing the isolation of both P-epimers in pure form for

several ligands. Steric and electronic tuning of the ligand

structure was accomplished by broad variation of the

alcohol or amine component, including also chiral struc-

tures. All new ligands were tested in the asymmetric

hydrogenation (Rh), allylic substitution (Pd), and hydro-

vinylation (Ni), for which the influence of the exocyclic O-

or N-substituent at the P-atom (phosphoramidite vs. phos-

phorodiamidite) and the interplay of the different chiral

centers in the Betti base backbone and the stereogenic

phosphorus donor were evaluated.

Scheme 2. Possible synthetic routes for the preparation of P-stereo-

genic phosphoramidites and phosphorodiamidites.

Route A involves first the formation of a PCl₂-intermedi-

ate (dichlorophosphite or dichloramidophosphite), which is

subsequently reacted with the amino alcohol to give the

phosphoramidite or phosphorodiamidite, respectively.

Here, the chirality at the phosphorus atom is generated in

the second step. Alternatively, Route B first entails the

synthesis of phosphoramidochloridite 20, which is

subsequently converted into the phosphoramidite or phos-

phorodiamidite by treatment with either an alcohol or a

Results and Discussion

Synthesis of Betti Bases

Betti base (R,R)-19 was synthesized from 2-naphthol, secondary amine. Thus, Route B involves the formation of

benzaldehyde, and (R)-phenylethylamine by mixing and a chiral center at the phosphorus atom in the first step of

heating all components at 60 °C for 14 h according to a the synthesis. The subsequent substitution of the chloride

reported procedure.^[31]The synthesis is diastereoselective, may lead to inversion, retention, or even racemization of

and (R,R)-19 was obtained in Ͼ 99% de and 82% yield the configuration at the phosphorus. Therefore, tempera-

(Scheme 1).

ture, solvent and hardness of the nucleophile can be impor-

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C. Schmitz, W. Leitner, G. Franciò

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tant to control the stereochemistry at the P-atom during

this synthesis route.

With the aim of developing a modular synthetic proto-

col, which also provides control of the P-chirality, both

routes were investigated and compared for phosphoramid-

ites and phosphorodiamidites. As will be shown in detail,

the two synthetic routes are not equivalent but complemen-

tary.

Synthesis of Phosphoramidites by Route A

The reaction of (R,R)-19 with commercially available

dichloro(methoxy)phosphine in the presence of triethyl-

amine in tetrahydrofuran (THF) led to the formation of

two phosphorus-containing species, as indicated by ³¹P{¹H}

NMR analysis (δ_P= 136.6 ppm; 119.7 ppm) in a ratio of

80:20. MS and NMR analyses revealed their identical con-

stitution but opposite configuration at the stereogenic phos-

phorus atom (Scheme 3).^[34]The large difference in ³¹P

NMR shifts of the P-epimers 21a indicates a significant dif-

ference in the environment at the P-atom.

Subsequent attempts to separate the P-epimers (S_P)-21a

and (R_P)-21a either by crystallization or by chromatog-

raphy were not successful. Therefore, the mixture of P-epi-

mers was treated with a solution of BH₃·SMe₂to give the

borane adducts 21a·BH₃(Scheme 3). The resulting air-

stable borane adducts were easily separated by column

chromatography (silica; pentane/ethyl acetate) to give (S_P)-

21a·BH₃(³¹P NMR: δ = 118.0 ppm) and (R_P)-21a·BH₃

(³¹P NMR: δ = 110.5 ppm) in 63 and 12% yield,^[35]respec-

tively. The configuration of the P-atom was assigned by X-

ray crystal structure analysis of suitable crystals of (S_P)-

21a·BH₃, obtained by slow solvent evaporation at room

temperature of an ethereal solution (Figure 6).

Figure 6. Molecular structure of (S_P)-21a·BH₃in the solid state as

determined from X-ray diffraction analysis. CCDC-1038401 con-

tains the supplementary crystallographic data for this paper. These

data can be obtained free of charge from The Cambridge Crystallo-

graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

geometry (sum of angles 654.50°), whereas the nitrogen

atom in the oxazaphosphacycle has a trigonal-planar geom-

etry (sum of angles 354.54°) and hence a high degree of sp²-

hybridization character (Table 2).

Table 1. Selected bond lengths [Å] in (S_P)-21a·BH₃.

P1–N1

P1–B1

1.6443

1.8876

P1–O1

P1–O2

1.6066

1.5826

Table 2. Selected bond angles [°] in (S_P)-21a·BH₃.

P1–N1–C11

P1–N1–C18

C11–N1–C18

O1–P1–O2

O1–P1–N1

117.83

120.89

115.82

96.20

O1–P1–B1

O2–P1–B1

N1–P1–B1

N1–P1–O2

114.02

114.26

116.89

109.06

104.07

In the solid state, the 1,3,2-oxaazaphosphorinane ring of

(S_P)-21a·BH₃adopts an arrangement between a boat and a

half-chair conformation. This is probably due to the incor-

The Betti base (R,S)-19 was used for the synthesis of

poration in the cycle of heteroatoms with two, three, and phosphoramidites, as described above, by dropwise addition

four coordination number and an annulated naphthyl moi- of a solution of dichloro(methoxy)phosphine in CH₂Cl₂to

ety. Additionally, a π-stacking of the phenyl ring of the a cold solution (0 °C) of (R,S)-19 and triethylamine in the

phenylethyl fragment and the naphthyl moiety is observed. same solvent. After 6 h, the two P-epimers (R_P)-22a and

The average distance between the centroids is 3.731 and (S_P)-22a were obtained in a 62:38 ratio and protected by

3.884 Å, respectively, and the angle between the planes of borane. Separation by column chromatography (silica;

the aryl rings is 13.8°. The bond lengths at the phosphorus pentane/ethyl acetate) yielded both borane-protected P-

atom are within the expected range, with the exocyclic O- epimers in 30 and 22% yield, respectively (Scheme 4).

atom exhibiting the shortest P–O bond length (Table 1).

The configuration of the P-atom was again assigned by

The phosphorus atom shows a nearly perfect tetrahedral X-ray crystal structure analysis of suitable crystals of (R_P)-

Scheme 3. Synthesis of phosphoramidites 21a starting from (R,R)-19 through Route A and protection as the borane adduct.

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P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

Scheme 4. Synthesis of phosphoramidite 22a starting from (R,S)-19 through Route A and protection as the borane adduct.

22a·BH₃obtained by slow solvent evaporation at room tem- Table 4. Selected bond angles [°] in (R_P)-22a·BH₃.

perature of an ethereal solution (Figure 7).

P1–N1–C1

P1–N1–C9

C1–N1–C9

O1–P1–O2

O1–P1–N1

119.85

118.86

114.94

101.22

105.07

O1–P1–B1

O2–P1–B1

N1–P1–B1

N1–P1–O2

111.28

114.56

118.19

104.77

the residue was washed with cold hexane to give phos-

phoramidites 21a and 22a in 64–97% yield (Scheme 5). De-

composition or epimerization of the P-configuration was

not observed during the deprotection.

Figure 7. Structure of (R_P)-22a·BH₃in the solid state as determined

from X-ray diffraction.CCDC-1038402 contains the supplementary

crystallographic data for this paper. These data can be obtained

free of charge from The Cambridge Crystallographic Data Centre

via www.ccdc.cam.ac.uk/data_request/cif.

Scheme 5. Deprotection of borane phosphoramidites 21a·BH₃and

22a·BH₃by reaction with diethylamine.

In the solid-state crystal structure of (R_P)-22a·BH₃, the

1,3,2-oxaazaphosphorinane ring does not exhibit a definite

conformation, as was also observed for (S_P)-21a·BH₃. The

conformation adopted is again between boat and half-chair,

but the half-chair conformation is more pronounced. A π-

stacking is not observed and the phenylethyl substituent is

oriented further away from the naphthyl moiety. All bond

lengths on the P-atom are in the expected range and com-

parable to the values observed in (S_P)-21a·BH₃. Again, the

exocyclic O-atom exhibits the shortest P–O bond length.

The phosphorus atom has a nearly perfect tetrahedral ge-

ometry (sum of angles 655.09°), whereas the N-atom dis-

plays a trigonal-planar geometry (sum of angles 353.65°)

(Table 3 and Table 4).

Synthesis of Phosphoramidites by Route B

After demonstrating that Route A was suitable for the

synthesis of the (S_P)-epimer starting from (R,R)-19,

Route B, comprising the generation of a phosphoramido-

chloridite in situ was evaluated by using different solvents

and bases (Scheme 6). Compound (R,R)-19 was dissolved

in THF and the solution was cooled to 0 °C. After the ad-

dition of triethylamine, a solution of phosphorus trichloride

was added slowly and the reaction was allowed to reach

room temperature. After 3 h, the reaction was complete, as

monitored by ³¹P NMR spectroscopy, and the two P-epi-

mers of phosphoramidochloridite 20 were formed in a 55:45

ratio [δ_P= 133.1 ppm (R_P); δ_P= 139.2 ppm (S_P)]. Methanol

was then added slowly in the presence of triethylamine at

0 °C. After 6 h at room temperature, full conversion was

achieved and phosphoramidites (R_P)-21a and (S_P)-21a were

obtained with a high preference for the (S_P)-epimer in a

ratio of 15:85, very similar to that obtained through

Table 3. Selected bond lengths [Å] in (R_P)-22a·BH₃.

P1–N1

P1–B1

1.6319

1.8795

P1–O1

P1–O2

1.6198

1.5876

To obtain the free ligands, diethylamine was added in Route A.^[36]

large excess to the borane-phosphoramidites 21a·BH₃and

When the same reaction sequence was carried out in

22a·BH₃and the resulting solutions were stirred for 3 h at CH₂Cl₂with the same base triethylamine, phosphoramido-

60 °C. Afterwards, all volatiles were removed in vacuo and chloridite 20 was formed in a similar R_P/S_Pratio of 60:40.

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Scheme 6. Synthesis of P-stereogenic phosphoramidites by Route B using different solvents and bases.

In the following reaction with methanol the P-epimers of 1-naphthol, and 2-naphthol, as well as chiral alcohols (R)-

the resulting phosphoramidite 21a were obtained in a R_P/ and (S)-1-phenylethanol, were utilized. By using THF/

S_Pratio of 70:30 (Scheme 6). Consequently, the reaction in nBuLi, phosphoramidites possessing (S_P)-configuration at

CH₂Cl₂predominantly provided the (R_P)-epimer, whereas the P-atom could be selectively prepared for all the alcohols

the reaction in THF led preferentially to the (S_P)-epimer. employed in the synthesis. The ligands were purified by fil-

The reactions in CH₂Cl₂proceeded more slowly than in tration through basic alumina to remove oxidized or hy-

THF; in particular, the formation of phosphoramido- drolyzed P-species and unreacted starting/intermediate ma-

chloridite 20. Additionally, an increased amount (usually terials. Afterwards, the ligands were protected by borane

10–20%) of side product 23, resulting from the reaction of and purified by column chromatography (silica; pentane/

phosphoramidochloridite 20 and (R,R)-Betti base 19, was ethyl acetate) to give (S_P)-21a–i·BH₃in 71–89% yield

observed (Scheme 7).

(Scheme 8).

Scheme 7. Formation of side product 23 from phosphoramido-

chloridite 20 and (R,R)-19 in CH₂Cl₂.

Finally, when (R,R)-19 was deprotonated using n-butyl-

lithium as base in THF at –78 °C and then reacted with

PCl₃, the stereoselective formation of (S_P)-phosphoramido-

chloridite (S_P)-20 was observed (Scheme 6). The reaction of

this intermediate (S_P)-20 with the lithiated alcohol MeOLi

at –78 °C led to the exclusive formation of (S_P)-21a. Thus,

Scheme 8. Synthesis of borane phosphoramidites possessing dif-

ferent alkoxy substituents through Route B.

The procedure in CH₂Cl₂using triethylamine as base was

the substitution of the chloride by the alkoxide proceeded used for the preparation of (R_P)-21 through the synthesis

with complete inversion^[36]of configuration at the P-atom, of a diastereomeric mixture followed by protection with

suggesting a S_N2-type mechanism. Hence, the same syn- BH₃and separation. The preference towards the (R_P)-epi-

thetic procedure using either CH₂Cl₂/NEt₃or THF/nBuLi mer, however, decreased with increasing steric bulk of the

gave selective access to both P-epimers of the methoxy sub- alcohols used for the synthesis. For example, the reaction

stituted phosphoramidite.

using ethanol as the alcohol moiety provided both P-epi-

As a next step, the spectrum of alcohols used for the mers in a R_P/S_Pratio of 60:40, whereas a 35:65 ratio was

synthesis of phosphoramidites was extended. In addition to achieved when isopropanol was utilized. In addition, the R_f

methanol, ethanol, isopropanol, tert-butanol, phenol, values of the two P-epimers became similar with increasing

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P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

Scheme 9. Deprotection of borane phosphoramidites 21a–i·BH₃using diethylamine.

steric demand of the alcohols used and, hence, the chroma- (S_P)-configuration have a chemical shift in the range of δ =

tographic separation was more difficult. As a consequence, 1.73–1.81 ppm (CH₃) and δ = 4.81–4.97 (CH), whereas the

only (R_P)-21a–d·BH₃could be successfully isolated in low ligands with (R_P)-configuration are shifted to higher field

to moderate yields of 21–38% (Scheme 9).

(δ = 1.46–1.53 ppm for CH₃, δ = 4.48–4.55 for CH). Very

1

Finally, the borane-phosphoramidites 21a–i·BH₃were pronounced differences were also observed for the H–³¹P

deprotected as described above by treatment with dieth- coupling constants of the two CH protons in the Betti base

ylamine. After the work-up, phosphoramidites 21a–i were backbone. Coupling constants in the range of ³J_H,P= 11.3–

obtained in 77–98% yield (Scheme 9). Again, decomposi- 12.0 Hz for the exocyclic C–H in the 1-phenylethyl moiety

3

tion or epimerization of the P-configuration was not ob- and J_H,P= 5.2–5.9 Hz for the endocyclic C–H were ob-

served during the deprotection.

served for the ligands with (S_P)-configuration, whereas the

Each P-epimer presented very characteristic chemical phosphoramidites with (R_P)-configuration showed a larger

shifts and coupling constants in ³¹P, ¹H, and ¹³C NMR coupling constant of ³J_H,P= 15.7–16.7 Hz for the exocyclic

1

spectra, and by comparison of these NMR data with that CH proton and no H–³¹P-coupling was observed for the

of (S_P)-21a, the structure of which was unequivocally deter- endocyclic CH proton. Similar trends were observed in the

mined by X-ray analysis, the P-configuration of all other ¹³C NMR spectra. Here, especially the ¹³C–³¹P coupling

deprotected ligands 21 was assigned. For example, ligands constants are indicative for the P-configuration.

21a–d with (S_P)-configuration, gave a chemical shift of δ =

131.9–136.6 ppm in the ³¹P NMR spectra, whereas ligands

possessing (R_P)-configuration exhibit a chemical shift of δ

Synthesis of Phosphorodiamidites

= 114.1–120.0 ppm (Figure 8). The chemical shifts in the

¹H NMR spectra also provide characteristic information,

The synthesis of phosphorodiamidites was also investi-

particularly for the signals of the CH- and the CH₃-group

gated by using both synthetic Routes A and B (Scheme 1).

of the phenylethyl moiety. In particular, the ligands with

By following Route A, the reaction of (R,R)-Betti base 19

with commercially available dichloro-N,N-diethylamino-

phosphine in CH₂Cl₂in the presence of triethylamine re-

sulted in a mixture of the two P-epimers (R_P)-24a (δ =

135.4 ppm) and (S_P)-24a (δ = 114.7 ppm) in a 25:75 ratio,

whereas when THF was used under the same conditions,

formation of the (R_P)-epimer of 24a was clearly favored

(R_P/S_Pratio 75:25). Subsequent addition of BH₃/SMe₂pro-

vided the borane adducts, which were separated by column

chromatography in 30 and 18% yield, respectively

(Scheme 10).

As already observed for the phosphoramidites, there was

a considerable spread in the ³¹P NMR chemical shift values

(ca. 20 ppm), thus indicating the significant differences in

the environment of the P-epimers of the phosphorodiamid-

ites. In comparison to the phosphoramidites, ³¹P NMR sig-

nals of the phosphorodiamidites were slightly shifted to

higher field.

Figure 8. Comparison of characteristic chemical shifts (¹H,³¹P) and

coupling constants (J_H,Pand J_C,P) for both P-epimers of phosphor-

amidites 21a–d.

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6211

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

Scheme 10. Synthesis of borane-protected phosphorodiamidites 24a·BH₃by following Route A.

The configuration of the P-atom was unambiguously as- Table 5. Selected bond lengths [Å] in (R_P)-24a·BH₃.

signed by X-ray diffraction analysis of suitable crystals of

(R_P)-24a·BH₃obtained by slow solvent evaporation at

P1–N1

P1–N2

1.6367

1.6593

P1–O1

P1–B1

1.6207

1.8864

room temperature from an ethereal solution (Figure 9).

Table 6. Selected bond angles [°] in (R_P)-24a·BH₃.

P1–N1–C1

P1–N1–C2

C1–N1–C2

P1–N2–C3

P1–N2–C11

C3–N2–C11

122.98

120.77

115.35

115.55

125.08

118.19

N1–P1–O1

N1–P1–N2

N1–P1–B1

N2–P1–O1

N2–P1–B1

O2–P1–B1

104.67

110.60

113.04

98.90

117.49

110.49

The synthesis of phosphorodiamidites through Route B

was investigated using THF as solvent and triethylamine as

base (Scheme 11). Both P-epimers of 24a were obtained in

a R_P/S_Pratio of 75:25, accompanied by the condensation

product 23 (ca. 10%). When the reaction was carried out

under kinetic control in THF at –78 °C using n-butyllithium

as base, the (R_P)-epimer was again obtained stereoselec-

tively.

Figure 9. Structure of (R_P)-24a·BH₃in the solid state as determined

from X-ray diffraction.CCDC-1038400 contains the supplementary

crystallographic data for this paper. These data can be obtained

free of charge from The Cambridge Crystallographic Data Centre

via www.ccdc.cam.ac.uk/data_request/cif.

It is important to note that the changes in CIP priority

of the substituent at the phosphorus results in opposite

stereodescriptors for the P-configuration of the phosphor-

odiamidites when compared with the phosphoramidites

with the same spatial arrangement. For example, superim-

posing the (R,R)-Betti scaffold, the exocyclic NEt₂-substitu-

ent in (R_P)-24a·BH₃will point in the same direction as the

OEt-substituent in (S_P)-21b·BH₃.

Scheme 11. Synthesis of phosphorodiamidites 24a following

Route B.

In summary, Route A, using CH₂Cl₂/NEt₃led preferen-

In the solid state, the oxazaphosphacycle in (R_P)- tially to the (S_P)-epimer of phosphorodiamidites, whereas

24a·BH₃exhibits a boat conformation and thus differs from Route B, using THF/nBuLi, provided stereoselective access

the arrangement observed for phosphoramidite (S_P)- to the (R_P)-epimer. These findings were used to establish

21a·BH₃. A π-stacking of the phenyl ring in the phenylethyl the conditions of the synthesis of phosphorodiamidites pos-

fragment and the naphthyl moiety is not present. The bond sessing different exocyclic amine substituents. In addition

lengths at the P-atom are within the expected range. In to diethylamine, diphenylamine and piperidine were uti-

comparison to the phosphoramidite (S_P)-21a·BH₃, the P1– lized, as well as the chiral amines (R)- and (S)-N-methyl-1-

O1 bond in (R_P)-24a·BH₃is significantly longer. The P1– phenylethylamine and (R,R)- and (S,S)-bis(1-phenylethyl)-

N1 bond is slightly shorter as compared with the P1–N2 amine.

bond in the oxazaphosphacycle. The phosphorus atom

Route B (THF/nBuLi) was used for the stereoselective

shows a nearly perfect tetrahedral geometry (sum of angles synthesis of the (R_P)-epimers via (S_P)-phosphoramido-

655.19°) whereas both N-atoms adopt a trigonal-planar ge- chloridite (S_P)-20 generated in situ and subsequent reaction

ometry (sum of angles 358.82°, 359.10°; Table 5 and with the respective lithiated amine. After filtration through

Table 6).

basic alumina, the ligands were treated with borane-dimeth-

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P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

ylsulfide complex and purified by column chromatography epimers, and separation by column chromatography (silica;

(silica; pentane/ethyl acetate) to give the borane-phos- pentane/ethyl acetate) (Scheme 13). Similar to the trend ob-

[37]

phorodiamidites (R_P)-24a–f·BH₃and (S_P)-24g·BH₃

54–94% yield (Scheme 12).

in served for the phosphoramidites, the selectivity towards the

(S_P)-epimer decreased with increasing steric demand of the

amine moiety. For instance, the P-epimers synthesized from

(R)-N-methyl-1-phenylethylamine were obtained in a ratio

of R_P/S_Pratio of 47:53, whereas the synthesis using (R,R)-

bis(1-phenylethyl)amine gave the P-epimers with a R_P/S_P

ratio of only 88:12. In addition, the R_f-values of the two P-

epimers converge with increasing steric bulk of the exocyclic

amine substituent and rendered the isolation of the minor

isomer arduous. Consequently, from the isomer mixture ob-

tained by this route, only (S_P)-24a–d·BH₃based on dieth-

ylamine, piperidine, and (R)- and (S)-N-methyl-1-phenyl-

ethylamine were successfully isolated (19–30% yield).

The BH₃-deprotection of phosphorodiamidites (R_P)-

24a–f·BH₃and (S_P)-24a–d,g·BH₃was realized by treatment

with a large excess of diethylamine at 60 °C, as described

above. The phosphorodiamidites were obtained in 84–99%

yield and without any epimerization during the deprotec-

tion procedure (Scheme 14).

Surprisingly, the deprotection was not effective for (R_P)-

Scheme 12. Stereoselective synthesis of borane phosphorodiamid-

[37]

and (S_P)-24b·BH₃and (S_P)-24g·BH₃. For the latter species,

decomposition was observed, whereas (R_P)- and (S_P)-

24b·BH₃did not undergo deprotection using diethylamine

ites (R_P)-24a–f·BH₃and (S_P)-24g·BH₃

by following Route B

(THF/nBuLi).

The (S_P)-epimers were obtained by Route A (CH₂Cl₂/ or other bases such as morpholine or 1,4-diazabicyclo[2.2.2]

NEt₃) via the respective dichloroaminophosphine formed in octane (DABCO). Alternatively, (R_P)-24b was prepared ac-

situ,^[38]subsequent borane-protection of the mixture of P- cording to Route B (THF/nBuLi) and used without further

Scheme 13. Synthesis of 24a–g·BH₃as mixtures of P-epimers by following Route A and their separation by column chromatography.

Scheme 14. Deprotection of borane phosphorodiamidites 24·BH₃by reaction with diethylamine.

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6213

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

manipulation (purity ca. 88% as determined by ³¹P NMR ation is dominated by the chiral information located at the

spectroscopic analysis) in catalysis.^[39]

carbon atoms of the ligand backbone rather than the chiral-

ity at the phosphorus atom. For the ligands possessing a

(S_P)-configuration, a decrease in enantioselectivity was ob-

served with increasing steric bulk of the alcohol moiety of

the ligand. The highest ee value of 70% (S) was achieved

by using the methyl-substituted ligand (S_P)-21a at very low

conversion (Table 7, entry 1). In case of the ligands with

(R_P)-configuration, an opposite trend was observed and the

enantiomeric excesses raised with increasing steric demand

of the exocyclic alkoxy substituents at the phosphorus atom

(entries 2, 4, 6, and 8). No clear tendency was observed

for ligands (S_P)-21e–i, which provided low conversions and

moderate enantioselectivities.

Rh-Catalyzed Hydrogenation

The newly synthesized P-stereogenic phosphoramidites

21a–i and 22a, and phosphorodiamidites 24a–f were tested

in a range of metal-catalyzed asymmetric transformations

for which chiral monodentate phosphorus ligands are estab-

lished lead structures. For the asymmetric hydrogenation of

dimethyl itaconate, the catalysts were prepared in situ from

[Rh(cod)₂]BF₄by using a rhodium/phosphorus ratio of

1:2.05, and the reactions were carried out under standard

conditions; the results are shown in Table 7.

Alteration of the stereochemistry on the backbone for

ligands 22a, synthesized from (R,S)-Betti base, was ob-

served to have a significant influence on the catalytic prop-

erties of this system (Table 7, entries 14 and 15). Whereas

(S_P)-21a provided only 4% conversion and 70% ee (S), the

diastereomer (S_P)-22a led to full conversion and 85% ee

(S). Higher enantioselectivity at low conversion was ob-

tained with (R_P)-22a (50% ee) as compared with (R_P)-21a

(31% ee). Interestingly, both of the latter phosphoramidites

promoted the preferential formation of the (R)-enantiomer

in contrast to all other ligands. Thus, the P-chirality ap-

pears to play a more important role in the enantiodiscrim-

ination when the steric demand of the exocyclic substituent

is particularly low.

A pronounced influence of the P-chirality on the catalyst

activity was also observed for the phosphorodiamidites

24a–f. For instance, the diethylamine substituted (R_P)-24a

led to full conversion, whereas only moderate conversion

was achieved with the epimeric ligand (S_P)-24a (Table 7, en-

tries 16 and 17). The opposite trend was observed for 24c

and 24d bearing the bulkier chiral N-methyl-1-phenyl-

ethylamine moiety for which the (R_P)-epimers were signifi-

cantly more active than the (S_P)-epimers. A further increase

of the steric hindrance of the amine synthon in (R_P)-24e

and (R_P)-24f resulted in almost inactive Rh-catalysts (en-

tries 23 and 24).

Table 7. Asymmetric hydrogenation of dimethyl itaconate.^[a]

Entry Ligand

Exocycl. subst.

(S_P)-21a OMe

(R_P)-21a OMe

Conv. [%]^[b]ee [%]^[c]

1

2

4

25

5

Ͼ 99

10

Ͼ 99

28

70 (S)

31 (R)

61 (S)

57 (S)

37 (S)

58 (S)

3 (S)

3

4

5

6

7

8

9

(S_P)-21b OEt

(R_P)-21b OEt

(S_P)-21c OiPr

(R_P)-21c OiPr

(S_P)-21d OtBu

(R_P)-21d OtBu

(S_P)-21e OPh

Ͼ 99

32

34

24

23

27

Ͼ 99

6

Ͼ 99

42

Ͼ 99

47

Ͼ 99

57

Ͼ 99

Ͻ 1

2

65 (S)

33 (S)

42 (S)

46 (S)

37 (S)

85 (S)

50 (R)

32 (S)

45 (S)

48 (S)

63 (S)

21 (S)

50 (S)

1 (S)

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

(S_P)-21f

(S_P)-21g O-2-naphthyl

(S_P)-21h (R)-O–CH(Me)Ph

(S_P)-21i

(S_P)-22a OMe

(R_P)-22a OMe

(R_P)-24a NEt₂

(S_P)-24a NEt₂

(R_P)-24b N-(CH₂)₅-

(R_P)-24c (R)-N(Me)–CH(Me)Ph

(S_P)-24c (R)-N(Me)–CH(Me)Ph

(R_P)-24d (S)-N(Me)–CH(Me)Ph

(S_P)-24d (S)-N(Me)–CH(Me)Ph

(R_P)-24e (R,R)-N[CH(Me)Ph]₂

(R_P)-24f (S,S)-N[CH(Me)Ph]₂

O-1-naphthyl

(S)-O–CH(Me)Ph

n.d.

7 (S)

Low to moderate enantiomeric excesses were achieved

with the phosphorodiamidite ligands 24, all of which led

preferentially to the (S)-enantiomer (Table 7, entries 16–24).

The configuration of the phosphorus has a minor impact

on the enantiodiscrimination, as was also observed in case

of the phosphoramidites. In general, an increase in the ste-

[a] Reaction conditions: substrate (3 mmol), sub/Rh/L

(1,000:1:2.05), CH₂Cl₂(2 mL), p(H₂) (40 bar), room temp., 14 h.

[b] Determined by GC analysis. [c] Determined by chiral GC analy-

sis.

Low conversions were obtained with all phosphoramid- ric demand of the amine substituent in (R_P)-24 results in

ites 21a–i possessing a (S)-configuration at the phosphorus slightly higher enantioselectivities (entries 16, 18, 19, and

atom (Table 7, entries 1, 3, 5, 7 and 9–13). In comparison, 21). A direct comparison of the P-epimers of 24c and 24d

the (R_P)-counterparts (entries 2, 4, 6, and 8) were signifi- based on the chiral (R)- or (S)-N-methyl-1-phenyleth-

cantly more active and the ligands bearing ethyl, isopropyl, ylamine, respectively, clearly show synergies of the different

or tert-butyl substituents led to full conversion. For both chiral centers (entries 19–22). The highest enantioselectivity

P-epimers, an increasing steric bulk of the alcohol moiety of all tested phosphorodiamidites (63% ee) was achieved by

resulted in higher activity.

using (R_P)-24c.

The ee values obtained were low to moderate. All phos-

phoramidite ligands favored the formation of the (S)-

enantiomer of the hydrogenation product with only two ex-

Pd-Catalyzed Allylic Substitution

P-Stereogenic phosphoramidites and phosphorodiamid-

ceptions (see below) indicating that the enantiodiscrimin- ites have been successfully applied in this transformation,

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P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

for which excellent enantioselectivities of up to 99% were 15). Poor enantioselectivity (17% ee) towards the S-product

achieved for the allylic amination, alkylation, and sulfon- was achieved with (R_P)-22a. Thus, as already observed in

ylation.^[12,18b,18g]

the hydrogenation, the combination of (R,S)-Betti base and

The newly synthesized ligands were tested in the Pd-cata- S_P-chirality resulted in the machted ligand structure for

lyzed asymmetric allylic amination of (rac)-(E)-1,3-di- (S_P)-22a (Table 8, cf. entry 14 with entries 15, 1, and 2).

phenylallyl acetate with benzylamine. The catalyst was gen-

The stereochemistry of the P-donor in the phosphoro-

erated in situ from [Pd(allyl)Cl]₂and the respective ligand diamidite ligands had a significant impact both on the cata-

with a palladium/phosphorus ratio of 1:2.1; the results are lyst activity and enantioselectivity. For instance, 48% con-

summarized in Table 8.

version and 40% ee (S) was obtained with (R_P)-24a,

whereas the use of (S_P)-24a led to full conversion and 70%

ee (R) (Table 8, entries 16 and 17). Of the four dia-

stereomers derived from N-methyl-1-phenylethylamine,

(R_P)-24c, (S_P)-24c, (S_P)-24d, and (R_P)-24d (entries 19–22),

the latter ligand possessed the matched structure for this

reaction leading to quantitative conversion and 83% ee (S).

Again, low conversions were observed with both dia-

stereomers derived from the bulky bis(1-phenylethyl)amine

(R_P)-24e and (R_P)-24f (entry 23–24).

Table 8. Asymmetric allylic amination of (rac)-(E)-1,3-diphenylallyl

acetate.^[a]

Entry Ligand

Exocyclic substituent

(S_P)-21a OMe

(R_P)-21a OMe

(S_P)-21b OEt

(R_P)-21b OEt

(S_P)-21c OiPr

(R_P)-21c OiPr

(S_P)-21d OtBu

(R_P)-21d OtBu

(S_P)-21e OPh

Conv. [%]^[b]ee [%]^[c]

1

2

3

4

5

6

7

8

Ͼ 99

39

91

Ͼ 99

67

73

Ͼ 99

58

97

93

22 (S)

44 (R)

38 (S)

22 (R)

23 (S)

12 (R)

13 (R)

16 (R)

48 (R)

54 (R)

51 (R)

55 (R)

17 (S)

78 (S)

11 (R)

40 (S)

70 (R)

32 (S)

37 (R)

26 (R)

83 (S)

n.d.

Ni-Catalyzed Hydrovinylation

The Ni-catalyzed hydrovinylation of styrene, in which a

single ligand is bound to the active metal species, was then

investigated. In particular, phosphoramidites have been

shown to provide catalyst systems with high levels of activi-

ties and enantioselectivities for this transformation,^[40,41]

whereas NOBIN-based P-stereogenic phosphorodiamidites

did not afforded active catalysts.^[24]

Nickel catalysts were generated in situ from the respec-

tive ligand, [Ni(allyl)Br]₂, and NaBArF as activator. Since

first exploratory studies indicated a very high activity for

these catalysts, the experiments were conducted at low tem-

perature (–50 °C) with a catalyst loading of 0.1 mol-%, and

the reactions were stopped after 20 min; the results are sum-

marized in Table 9.

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

(S_P)-21f

(S_P)-21g O-2-naphthyl

(S_P)-21h (R)-O–CH(Me)Ph

(S_P)-21i

(S_P)-22a OMe

(R_P)-22a OMe

(R_P)-24a NEt₂

(S_P)-24a NEt₂

(R_P)-24b N-(CH₂)₅-

(R_P)-24c (R)-N(Me)–CH(Me)Ph

(S_P)-24c (R)-N(Me)–CH(Me)Ph

(R_P)-24d (S)-N(Me)–CH(Me)Ph

(S_P)-24d (S)-N(Me)–CH(Me)Ph

(R_P)-24e (R,R)-N[CH(Me)Ph]₂

(R_P)-24f (S,S)-N[CH(Me)Ph]₂

O-1-naphthyl

(S)-O–CH(Me)Ph

48

Ͼ 99

90

56

18

Ͼ 99

2

12

6 (S)

6

45 (S)

In general, the catalyst activity with the phosphoramidite

ligands bearing alkoxy substituents correlated inversely

with the steric demand of the alcohol moiety irrespective of

the configuration at the P-donor (Table 9, entries 1–8).

Thus, ligands (S_P)-21a and (R_P)-21a, bearing the smallest

[a] Reaction conditions: substrate (0.75 mmol), sub/Pd/L

(50:1:1.05), CH₂Cl₂(2 mL), room temp., 36 h. [b] Determined by

¹H NMR spectroscopic analysis. [c] Determined by chiral HPLC

analysis.

Independently of the stereochemistry at the P-donor, group (i.e., OMe), provided the highest activity and gave

high conversions were obtained with most phosphoramid- almost full conversion within 20 min, corresponding to a

ites 21a–i, especially with those ligands possessing sterically TOF_avof 3000 h^–1(entries 1 and 2). High selectivities

less demanding alkoxy groups (Table 8, entries 1–13). The (Ն 97%) towards the desired product 3-phenyl-1-butene

configuration at the phosphorus atom played a dominant were obtained with all tested phosphoramidite ligands, indi-

role in the enantiodiscrimination for the ligands with small cating that the corresponding catalysts did not promote

alkoxy substituents. In particular, the (S_P)-diastereomer consecutive reactions (isomerization or oligomerization)

produced the (S)-enantiomer preferentially, whereas the li- under these conditions even at high conversions.

gands with (R_P)-configuration gave the (R)-product (en-

The preferred stereochemistry of the product was deter-

tries 1–6). Low ee values were obtained with both tBu-sub- mined by the configuration of the P-donor, where ligands

stituted ligands (R_P)- and (S_P)-21d, whereas enantio- possessing (S_P)-configuration favored the formation of the

selectivities around 50% ee were achieved with the aryloxy (R)-product, and diastereomers with (R_P)-configuration af-

derivatives (S_P)-21e–g and (S_P)-21h, bearing the chiral (R)- forded the (S)-product. Similar observations have been

1-phenylethoxy group.

made in the Pd-catalyzed allylic substitution and are again

Similar high conversions and very different enantio- in contrast to the results obtained in the Rh-catalyzed

selectivities have been observed for the phosphoramidites hydrogenation for which the configuration at the P-atom

derived from the (R,S)-Betti base (Table 8, entries 14 and had a large impact on the catalyst activity but a minor in-

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6215

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

Table 9. Asymmetric hydrovinylation of styrene.^[a]

93% conversion within 20 min accompanied by 98% selec-

tivity and 66% ee (S) (Table 9, entry 17). Slightly higher

enantioselectivity of 68% ee (S) and 99% selectivity at 84%

conversion were achieved with (S_P)-24c, containing the chi-

ral (R)-N-methyl-phenylethylamine (entry 20).

Entry Ligand

Exocyclic substituent

(S_P)-21a OMe

(R_P)-21a OMe

Conv. [%]^[b]p:i:o^[b]

ee [%]^[c]

Conclusions

1

2

97

Ͼ 99

72

67

66

54

36

20

5

98:1:1

96:3:1

98:1:1

99:0:1

100:0:0 12 (S)

100:0:0 5 (R)

100:0:0 56 (S)

100:0:0 21 (R)

13 (R)

27 (S)

15 (R)

24 (S)

7 (R)

A library of novel phosphoramidite and phosphorodi-

amidite ligands based on chiral Betti bases has been pre-

pared through a modular synthetic one-pot procedure from

readily available starting materials. The new ligands possess

a stereogenic phosphorus atom, and thus each ligand can

be formed as a mixture of two P-epimers. We have shown

that the ratio between the two P-epimers can be controlled

to a large extent by the selected synthetic route and the

reaction parameters (i.e., solvent, base, temperature).

Both P-epimers of the phosphoramidites could be ac-

cessed by using Route B, which comprises the formation of

the phosphoramidochloridite of the Betti base as key inter-

mediate. The (R_P)-epimer was obtained preferentially when

the reaction of the phosphoramidochloridite with the corre-

sponding alcohol was performed in CH₂Cl₂using triethyl-

amine as base. In contrast, when the reaction was carried

out under kinetic control using THF as solvent and n-butyl-

lithium as base at –78 °C, the (S_P)-epimer was obtained

stereoselectively. The latter procedure was also used for the

synthesis of phosphorodiamidites, where the (R_P)-epimer

was selectively obtained. For the preferential synthesis of

the (S_P)-epimer of the phosphorodiamidites, the reaction

via the dichloramidophosphite (Route A) was the most suit-

able.

3

(S_P)-21b OEt

4

(R_P)-21b OEt

5

(S_P)-21c OiPr

6

(R_P)-21c OiPr

7

(S_P)-21d OtBu

8

(R_P)-21d OtBu

9

(S_P)-21e OPh

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

(S_P)-21f O-1-naphthyl

(S_P)-21g O-2-naphthyl

(S_P)-21h (R)-O–CH(Me)Ph

(S_P)-21i (S)-O–CH(Me)Ph

(S_P)-22a OMe

(R_P)-22a OMe

(R_P)-24a NEt₂

(S_P)-24a NEt₂

(R_P)-24b N-(CH₂)₅-

(R_P)-24c (R)-N(Me)–CH(Me)Ph 51

(S_P)-24c (R)-N(Me)–CH(Me)Ph 84

(R_P)-24d (S)-N(Me)–CH(Me)Ph 40

(S_P)-24d (S)-N(Me)–CH(Me)Ph 11

(R_P)-24e (R,R)-N[CH(Me)Ph]₂

(R_P)-24f (S,S)-N[CH(Me)Ph]₂

15

24

57

81

23

Ͼ 99

30

93

37

98:1:1

97:1:2

97:2:1

98:1:1

93:6:1

91:7:2

98:2:0

98:1:1

94:6:0

99:1:0

92:8:0

26 (R)

21 (R)

4 (S)

2 (R)

7 (R)

18 (R)

18 (S)

66 (S)

32 (S)

41 (S)

68 (S)

29 (S)

100:0:0 47 (S)

n.d.

Ͻ 1

n.d.

[a] Reaction conditions: substrate (12 mmol), sub/Ni/L/NaBArF

(1000:1:1.02:1.05), CH₂Cl₂(2.5 mL), p(C₂H₄) (1.2 bar), –50 °C,

20 min. [b] p:i:o = product/isomers/oligomers; determined by GC

analysis with ethylbenzene as internal standard. [c] Determined by

chiral GC analysis.

fluence in the enantioselectivity. Low to moderate enantio-

The P-epimers were separated by column chromatog-

selectivities have been achieved with the phosphoramidite raphy as their borane adducts and subsequently deprotected

ligands and a clear trend with respect to the steric demand by reaction with diethylamine. The configuration at the P-

of the alkoxy substituent was not observed. Furthermore, stereocenter was assigned by X-ray diffraction analysis of

the change in the configuration of the Betti base backbone the borane adducts of two phosphoramidites and a phos-

from (R,R) to (R,S) in (S_P)-22a and (R_P)-22a did not result phorodiamidite ligand. By comparison of the characteristic

in a major improvement compared with (S_P)-21a and (R_P)- NMR chemical shifts and coupling constants, the configu-

21a (cf Table 9, entries 1–2 and 14–15). The best result was ration at the phosphorus of all other ligands was assigned.

obtained by using (R_P)-21d, with 56% ee (S) and full selec-

The new ligands were evaluated in three metal-catalyzed

tivity towards the desired product (entry 8).

asymmetric transformations, and the role of the exocyclic

The phosphorodiamidites provided similar activities and amine or alcohol substituent was examined as well as the

selectivities to those of the phosphoramidites, with the ex- interplay of the different chiral elements (Betti base back-

ception of (R_P)-24e and (R_P)-24f, which did not generate bone, P-stereochemistry, and chirality at the exocyclic sub-

active catalysts under the conditions applied (Table 8, en- stituent, if present). Considering the broad structural varia-

tries 16–24). No clear relationship between the steric de- tion of the ligands and the very diverse catalytic applica-

mand of the exocyclic amine substituent and the catalyst tions chosen, involving different metals and active species

activity was observed for this transformation. In contrast with two phosphorus ligands at the metal center (hydrogen-

to the phosphoramidites, all phosphorodiamidites led to the ation and allylic alkylation) or with only one (hydrovinyl-

formation of the (S)-enantiomer preferentially and indi- ation), no general guidelines but rather trends can be iden-

cated that the enantiodiscrimination was dominated by the tified within similar ligand structures and for each catalytic

configuration of the ligand backbone. The phosphorodi- application.

amidites with (S_P)-configuration led to higher enantiomeric

In the Rh-catalyzed hydrogenation, a large impact of the

excesses compared with their (R_P)-epimers. In more detail, P-chirality on the catalyst activity was observed, whereas

the diethylamino-substituted ligand (S_P)-24a gave the most the influence on the enantioselectivity was more subtle.

active catalyst among the tested phosphorodiamidites, with Using the optimum combination of the chirality at the Betti

6216

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Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

ogy. THF, diethyl ether and NEt₃were distilled from KOH and

dried with molecular sieves. PCl₃was freshly distilled. CDCl₃was

degassed through freeze-pump-thaw cycles and stored over molec-

ular sieves. All solvents and substances were stored over molecular

sieves under an atmosphere of argon. Silica gel (SiO₂60, 0.04–

0.063 mm, 230–400 mesh) and basic alumina (Al₂O₃90 basic, pH

8.5–10.5, 0.063–0.2 mm) were purchased from Roth. [Ni(allyl)Br]₂

was prepared according to a reported procedure.^[42]All other chem-

icals were purchased from Sigma–Aldrich, ABCR, TCI, or Alfa-

Aesar and used as received.

base, P-stereochemistry, and the smallest OMe exocyclic

substituent in (S_P)-22a turned out to be decisive for ob-

taining good enantioselectivities (85% ee).

High conversions were obtained in the Pd-catalyzed all-

ylic alkylation with most ligands. The configuration at the

P-donor exerted a major control on the enantioselectivity

when ligands with small substituents were applied. Two

very different ligands afforded the best results as the

“small” methoxy substituted phosphoramidite (S_P)-22a

(97% conv., 78% ee) and the bulky phosphorodiamidite li-

gand (R_P)-24d bearing the chiral group (R)-N-methyl-1-

phenylethylamine as exocyclic substituent (99% conv., 83%

ee) were the most selective catalysts.

General Procedure for the Synthesis of Borane-Protected Phos-

phoramidite and Phosphorodiamidite Ligands via in-situ-Generated

Phosphoramidochloridite Using n-Butyllithium (GP-Syn1): 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

In the Ni-catalyzed hydrovinylation, low enantio- (4.0 mmol, 1.0 equiv.) was dissolved in THF (15 mL) and the solu-

tion was cooled to –78 °C. n-Butyllithium (1.6 m in hexanes,

2.0 equiv.) was added dropwise within 15 min and the mixture was

stirred for 1 h at –78 °C and 1 h at room temperature. The solution

was cooled again to –78 °C and a solution of phosphorous trichlor-

ide (1.05 equiv.) in THF (5 mL) was added dropwise within 20 min.

The mixture was stirred for 1.5 h at –78 °C and then allowed to

slowly reach room temperature. After another 1.5 h at room tem-

perature, all volatiles were removed under reduced pressure. THF

(10 mL) was added to the residue, and the resulting suspension was

filtered through a PTFE membrane. In another Schlenk flask the

selectivities were achieved with phosphoramidite ligands for

which the configuration at the P-donor determined the pre-

ferred chirality of the product. However, this exerted no

influence on the catalytic activity. The more bulky phos-

phorodiamidites were superior in this reaction and high

chemo- (98–99%) and enantioselectivities (66–68% ee) at

high conversion (84–93%) were obtained both with the

NEt₂and (S)-N-methyl-1-phenylethylamine substituted li-

gand (S_P)-24a and (S_P)-24c, respectively.

As a general observation, the influence of the P-chirality respective alcohol (1.0 equiv.) or amine (1.0 equiv.) was dissolved

in THF (10 mL) and n-butyllithium (1.6 m in hexanes, 1.0 equiv.)

was added dropwise within 15 min. The mixture was stirred for 1 h

at –78 °C and 1 h at room temperature. The solution was cooled

again to –78 °C and the solution of the phosphoramidochloridite

was added dropwise within 20 min. The mixture was stirred for 1 h

at –78 °C and then allowed to slowly reach room temperature. After

1–3 h at room temperature, the solution was concentrated to a vol-

ume of 10 mL and filtered through basic alumina. After elution

with THF (5 mL), borane–dimethylsulfide complex (2.0 m in THF,

1.5 equiv.) was added and the mixture was stirred overnight at

was significant and even became the dominating factor for

the enantiodiscrimination and/or for the catalyst activity,

when alkoxy- or amine-substituents with low steric demand

were incorporated into the ligand structure. When chiral

moieties are included in the structure, additional synergistic

effects of the different chiral elements were observed lead-

ing to individual matched combinations for each catalytic

application.

In conclusion, we have demonstrated that chiral Betti

bases provide an easily accessible and versatile synthon for room temperature. All volatiles were removed under reduced pres-

sure to give a colorless foam, which was dried under high vacuum

for 3 h and then subjected to column chromatography (silica; pent-

ane/ethyl acetate, 4:1). After removal of the solvent, the borane-

protected ligands were obtained as colorless solids. Recrystalli-

zation from diethyl ether by slow evaporation of the solvent re-

sulted in colorless crystals that were suitable for X-ray crystal struc-

ture analysis.

the synthesis of diverse phosphorus ligands with good

properties in catalysis. The impact of the P-stereochemistry

in phosphoramidite and phosphorodiamidite ligands was

assessed in detail in this study. The ease of manipulation of

the lead structure allows for a great variety for tailoring the

ligand features. For instance, the use of this backbone for

bidentate phosphorus ligands is under investigation in our

group and will be reported in due course.

General Procedure for the Synthesis of Borane-Protected Phos-

phoramidite and Phosphorodiamidite Ligands via in-situ-Generated

Phosphoramidochloridite Using Triethylamine (GP-Syn2): 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) was dissolved in THF or CH₂Cl₂(10 mL)

and triethylamine (2.5 equiv.) was added. The solution was cooled

to 0 °C and a solution of phosphorous trichloride (1.02 equiv.) in

THF or CH₂Cl₂was added dropwise within 15 min. The mixture

was stirred for 1 h at 0 °C and overnight at room temperature. All

volatiles were removed under reduced pressure and the residue was

redissolved in either THF or CH₂Cl₂(10 mL) and the solution was

Experimental Section

General Considerations: All reactions and manipulations were per-

formed either using standard Schlenk techniques or in a glovebox

1

under an argon atmosphere. H, ¹³C, and ³¹P NMR spectra were

recorded with a Bruker AV 600 (600, 150 and 243 MHz, respec-

tively), Bruker AV 400 (400, 100, 162 MHz, respectively), or Bruker

AV 300 (300, 75, 121 MHz, respectively). Chemical shifts were ref-

erenced to residual solvent peaks (¹H NMR, ¹³C NMR) or H₃PO₄cooled to 0 °C. A solution of the respective alcohol (1.0 equiv.) or

85% as external standard (³¹P NMR). Mass spectra were recorded

with a Finnigan MAT 8200 (MS + HRMS-EI) or a Bruker

FTICR-Apex III (HRMS-ESI). Optical rotations were measured

with a Jasco P-1020 polarimeter. The concentrations used for meas-

amine (1.0 equiv.) and triethylamine (1.5 equiv.) in THF or CH₂Cl₂

(5 mL) was added dropwise within 15 min. The mixture was stirred

for 1 h at 0 °C and 1–16 h at room temperature. Toluene (1 mL)

was added and all volatiles were removed under high vacuum. The

uring specific rotations are given as grams per 100 mL. CH₂Cl₂, residue was dissolved in THF (8 mL) and filtered through basic

toluene, and n-pentane were dried with alumina and molecular alumina. After elution with THF (5 mL), borane–dimethylsulfide

sieves with a solvent purification system from Innovative Technol- complex (2.0 m in THF, 1.5 equiv.) was added and the mixture was

Eur. J. Org. Chem. 2015, 6205–6230

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6217

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

stirred overnight at room temperature. All volatiles were removed

under reduced pressure to give a colorless foam, which was dried

under high vacuum for 3 h and then subjected to column

chromatography (silica; pentane/ethyl acetate, 9:1). After removal

of the solvent, the borane-protected phosphorus-epimers were ob-

tained as colorless solids. Recrystallization from diethyl ether by

slow evaporation of the solvent resulted in colorless crystals that

were suitable for X-ray crystal structure analysis.

12.0 mmol, 1000 equiv.) and a solution of NaBAr^F(11.2 mg,

12.6 μmol, 1.05 equiv.) in CH₂Cl₂(0.5 mL) were added sequen-

tially, leading to a deep-red or purple solution. The reaction mix-

ture was saturated with ethylene and stirred for 20 min. The ethyl-

ene pressure was kept constant at 1.2 bar within the reaction. The

reaction was quenched by addition of aqueous ammonia (8 mL).

The organic phase was washed with water (3ϫ 2 mL), dried with

sodium sulfate, and analyzed by GC (ethylbenzene as internal stan-

dard) and chiral GC.

General Procedure for the Synthesis of Borane-Protected Phos-

phorodiamidite Ligands via in-situ-Generated Dichlorophosphine

Using Triethylamine (GP-Syn3): To a solution of phosphorus tri-

chloride (2.04 mmol, 1.02 equiv.) in either CH₂Cl₂or THF

(10 mL), was added triethylamine (1.5 equiv.) and the solution was

cooled to 0 °C. A solution of the respective amine (1.0 equiv.) in

CH₂Cl₂or THF (5 mL) was added dropwise within 5 min and the

mixture was stirred for 15 min at 0 °C and 2–6 h at room tempera-

ture. Toluene (1 mL) was added and all volatiles were removed at

high vacuum. The residue was redissolved in CH₂Cl₂or THF

(8 mL) and the solution was cooled to 0 °C. A solution of 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(1.0 equiv.) and triethylamine (2.5 equiv.) in CH₂Cl₂or THF

(10 mL) was added dropwise within 15 min and the mixture was

stirred for 1 h at 0 °C and overnight at room temperature. Toluene

(1 mL) was added and all volatiles removed under high vacuum.

THF (10 mL) was added to the residue, and the resulting suspen-

sion was filtered through a PTFE membrane and basic alumina

consecutively. After elution with THF (5 mL), the borane–dimeth-

ylsulfide complex (2.0 m in THF, 1.5 equiv.) was added and the

mixture was stirred overnight at room temperature. All volatiles

were removed under reduced pressure to give colorless foam, which

was dried under high vacuum for 3 h and then subjected to column

chromatography (silica; pentane/ethyl acetate, 9:1). After removal

of the solvent, the borane-protected phosphorus-epimers were ob-

tained as colorless solids. Recrystallization from diethyl ether by

slow evaporation of the solvent resulted in colorless crystals that

were suitable for X-ray crystal structure analysis.

General Procedure for the Catalytic Asymmetric Allylic Amination:

To a solution of [Pd(allyl)Cl]₂(5.5 mg, 15.0 μmol, 1.0 equiv.) in

CH₂Cl₂(1 mL) was added a solution of the ligand (31.5 μmol,

2.1 equiv.) in CH₂Cl₂(1 mL) and the mixture was stirred for 30 min

at room temperature. (rac)-(E)-1,3-Diphenylallyl acetate (189.2 mg,

750 μmol, 50 equiv.) was added and the solution was stirred for

15 min. Benzylamine (245 μL, 2.25 mmol, 150 equiv.) was added

and the mixture was stirred for 36 h at room temperature. The

reaction was stopped by removal of all volatiles at high vacuum

and the residue was analyzed by NMR and chiral HPLC (after

purification by column chromatography).

1-((R)-Phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

[(R,R)-19]: 2-Naphthol (14.5 g, 100.3 mmol, 1.0 equiv.) was dis-

solved in benzaldehyde (12.1 mL, 120.0 mmol, 1.2 equiv.), (R)-

phenylethylamine (13.3 mL, 105.0 mmol, 1.05 equiv.) was added,

and the mixture was gently stirred for 30 min at room temperature

and overnight at 60 °C, leading to a solid material. After cooling

to room temperature. ethanol (15–25 mL) was added and the mix-

ture was ground in a mortar. The resulting suspension was filtered

through a frit and the remaining solid was washed with small por-

tions of ethanol (8ϫ 10 mL). The residue was dried at 50 °C under

high vacuum overnight. The product was obtained as a colorless

solid, yield 30.1 g (82.3 mmol, 82.1 %). ¹H NMR (400 MHz,

CDCl₃): δ = 1.46 (d, J_H,H= 6.8 Hz, 3 H, CH₃), 2.26 (br. s, 1 H,

NH), 3.86 (q, J_H,H= 6.7 Hz, 1 H, CH), 5.43 (s, 1 H, CH), 7.17 (m,

10 H, Ar), 7.34 (m, 4 H, Ar), 7.70 (m, 2 H, Ar), 13.71 (br. s, 1 H,

OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 22.9 (CH₃), 56.6

(CH), 60.2 (CH), 113.0 (C_q, Ar), 120.0 (CH, Ar), 121.1 (CH, Ar),

122.4 (CH, Ar), 126.3 (CH, Ar), 126.7 (2ϫCH, Ar), 127.6 (2ϫCH,

Ar), 127.8 (CH, Ar), 127.9 (CH, Ar), 128.6 (C_q, Ar), 128.7 (CH,

Ar), 128.9 (2ϫCH, Ar), 129.0 (2ϫCH, Ar), 129.7 (CH, Ar), 132.6

(C_q, Ar), 141.4 (C_q, Ar), 143.0 (C_q, Ar), 157.3 (C_q, Ar) ppm. The

analytical data are in accordance with the literature.^[44]

General Procedure for the Deprotection of Borane-Protected Ligands

(GP-Syn4): The borane-protected ligand (typically ca. 1.0 mmol)

was dissolved in diethylamine (3–5 mL)^[43]and the solution was

warmed to 60 °C for 3–18 h. After cooling to room temperature,

all volatiles were removed under reduced pressure and the residue

was dried at 60 °C and high vacuum for 3 h. The residue was

washed with (cold) n-hexane (3ϫ 3 mL) and finally dried at high

vacuum to yield the ligand as colorless solid or highly viscous oil,

which crystallized upon standing.

1-((S)-Phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

[(R,S)-19]: 2-Naphthol (14.5 g, 100.3 mmol, 1.0 equiv.) was dis-

solved in benzaldehyde (12.1 mL, 120.0 mmol, 1.2 equiv.). The

solution was cooled to 0 °C and (R)-phenylethylamine (13.3 mL,

105.0 mmol, 1.05 equiv.) was added. The mixture was gently stirred

for 20 min at 0 °C and for 48 h at room temperature, leading to

a viscous material. The (R,S)-diastereomer was isolated in three

different manners. Method A: Ethanol (2–5 mL) was added care-

fully until a colorless precipitate formed. The precipitate [(R,R)-

diastereomer] was collected by filtration. The mother liquor was

concentrated at the rotary evaporator until a colorless precipitate

[(R,S)-diastereomer] formed. The precipitate was collected by fil-

tration, washed with small portions of ethanol and dried under

high vacuum. The product was obtained as a colorless solid (2.46 g,

7.0 mmol, 6.9%). Method B: Ethanol (15 mL) was added slowly,

leading to a colorless precipitate. The precipitate (mixture of dia-

stereomers) was collected by filtration and the filtrate left at room

temperature overnight, leading to a crystalline precipitate [(R,S)-

General Procedure for the Catalytic Hydrogenation of Dimethyl

Itaconate: To a solution of [Rh(cod)₂]BF₄(1.22 mg, 3.0 μmol,

1.0 equiv.) in CH₂Cl₂(1 mL) was added a solution of the ligand

(6.15 μmol, 2.05 equiv.) in CH₂Cl₂(1 mL). The mixture was stirred

for 15 min at room temperature and then transferred into a 10 mL

stainless steel autoclave, equipped with a glass inlet, magnetic stir-

ring bar, and containing dimethyl itaconate (474.5 mg, 3.0 mmol,

1000 equiv.), under an argon atmosphere. After stirring for 10 min,

the autoclave was pressurized with hydrogen (40 bar) and the mix-

ture was stirred for 14 h at room temperature. After carefully releas-

ing the pressure, the reaction mixture was filtered through a short

plug of silica and analyzed by NMR and chiral GC.

General Procedure for the Catalytic Hydrovinylation of Styrene: To

a solution of [Ni(allyl)Br]₂(2.16 mg, 6.0 μmol, 0.5 equiv.) in

CH₂Cl₂(1 mL) was added a solution of the ligand (12.2 μmol,

1.02 equiv.) in CH₂Cl₂(1 mL). The solution was stirred for 15 min diastereomer], which was also collected by filtration, washed with

at room temperature and then cooled to –50 °C. Styrene (1.37 mL, ethanol, and dried under high vacuum. The product was obtained

6218

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Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

as a colorless solid (1.35 g, 3.8 mmol, 3.8%). Method C: Ethanol

(30 mL) was added slowly, leading to a colorless precipitate. The

precipitate was collected by filtration, washed with ethanol (8ϫ

10 mL) and dried at high vacuum. The residue was recrystallized

several times from boiling toluene or acetonitrile and the crystalline

product [diastereomerically enriched/pure (R,S)-diastereomer] was

collected. After drying under high vacuum, the product was ob-

tained as colorless crystalline solid (1.91 g, 5.4 mmol, 5.4%). [α]²_D⁶

CH, Ar), 120.3 (d, J = 9.0 Hz, C_q, Ar), 121.8 (CH, Ar), 124.5 (CH,

Ar), 126.6 (CH, Ar), 127.3 (CH, Ar), 127.5 (2ϫCH, Ar), 127.6

(CH, Ar), 127.9 (2 ϫ CH, Ar), 128.25 (2 ϫ CH, Ar), 128.30

(3ϫCH, Ar), 129.7 (CH, Ar), 129.98 (C_q, Ar), 130.02 (C_q, Ar),

139.0 (d, J = 4.2 Hz, C_q, Ar), 140.9 (C_q, Ar), 147.5 (d, J = 9.1 Hz,

C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 118.0 ppm.

Borane Adduct of (1R,3R)-3-Methoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-

21a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn2 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(4.0 mmol, 1.0 equiv.) and methanol (4.4 mmol, 1.1 equiv.). The

product was obtained as a colorless solid, yield 517.9 mg

(1.21 mmol, 30%). ¹H NMR (400 MHz, CDCl₃): δ = 1.36 (d, ³J_H,H

1

= 191.9 (c = 0.5, CH₂Cl₂). H NMR (400 MHz, CDCl₃): δ = 1.56

(d, J_H,H= 6.7 Hz, 3 H, CH₃), 3.96 (q, J_H,H= 6.7 Hz, 1 H, CH),

5.86 (s, 1 H, CH), 7.12 (d, J_H,H= 8.9 Hz, 1 H, Ar), 7.16–7.42 (m,

12 H, Ar), 7.69 (m, 3 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 21.0 (CH₃), 55.4 (CH), 60.1 (CH), 114.3 (C_q, Ar),

120.2 (CH, Ar), 121.0 (CH, Ar), 122.4 (CH, Ar), 126.5 (3ϫCH,

Ar), 127.5 (CH, Ar), 127.87 (2ϫCH, Ar), 127.94 (CH, Ar), 128.59

(C_q, Ar), 128.64 (2ϫCH, Ar), 128.8 (CH, Ar), 129.0 (2ϫCH, Ar),

129.7 (CH, Ar), 132.3 (C_q, Ar), 141.3 (C_q, Ar), 143.0 (C_q, Ar),

156.6 (C_q, Ar) ppm. MS (EI): m/z (%) = 354.2 (30), 353.2 (69),

233.1 (16), 232.1 (50), 231.1 (100), 202.1 (11), 106.1 (13), 105.1 (10).

HRMS (ESI): m/z calcd. for C₂₅H₂₄NO⁺[M + H]⁺354.18524;

found 354.18445.

3

= 7.1 Hz, 3 H, CH₃), 3.71 (d, J_H,H= 11.4 Hz, 3 H, OCH₃), 5.09

(dq, ³J_H,H= 6.9, ³J_H,P= 11.8 Hz, 1 H, CH), 5.66 (d, ³J_H,P= 9.1 Hz,

1 H, CH), 7.10–7.45 (m, 11 H, Ar), 7.52 (m, 3 H, Ar), 7.74 (m, 2

H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.2 (d, J =

4.1 Hz, CH₃), 54.1 (d, J = 1.9 Hz, OCH₃), 54.3 (d, J = 3.1 Hz,

CH), 55.2 (d, J = 12.7 Hz, CH), 119.4 (d, J = 3.5 Hz, CH, Ar),

121.7 (CH, Ar), 124.5 (d, J = 11.4 Hz, C_q, Ar), 125.1 (CH, Ar),

127.1 (2ϫCH, Ar), 127.2 (CH, Ar), 127.6 (CH, Ar), 127.8 (CH,

Ar), 128.0 (2ϫCH, Ar), 128.7 (4ϫCH, Ar), 129.0 (CH, Ar), 129.4

(C_q, Ar), 130.0 (CH, Ar), 131.2 (C_q, Ar), 139.6 (d, J = 2.7 Hz, C_q,

Ar), 143.5 (C_q, Ar), 144.1 (d, J = 9.8 Hz, C_q, Ar) ppm. ³¹P{¹H}

NMR (162 MHz, CDCl₃): δ = 110.5 ppm.

(1R,3S)-3-Chloro-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-20]: 1-((R)-Phenyl{[(R)-

1-phenylethyl]amino}methyl)naphthalen-2-ol (1.77 g, 5.01 mmol,

1.0 equiv.) was dissolved in THF (15 mL) and the solution was

cooled to –78 °C. n-Butyllithium (2.5m in hexanes, 10.25 mmol,

4.1 mL, 2.0 equiv.) was added dropwise within 15 min and the mix-

ture was stirred for 1 h at –78 °C and 1 h at room temperature. The

solution was cooled again to –78 °C and a solution of phosphorus

trichloride (5.10 mmol, 0.48 mL, 1.1 equiv.) in THF (5 mL) was

added dropwise within 15 min. The mixture was stirred for 1.5 h

at –78 °C and for 2 h at room temperature. All volatiles were re-

moved under reduced pressure and the residue was redissolved in

THF (10 mL) and filtered through Celite. The solvent was removed

under reduced pressure and the residue was dried under high vac-

uum. The product was obtained as a colorless solid, yield 1.87 g

(4.47 mmol, 89%). ¹H NMR (400 MHz, CDCl₃): δ = 1.71 (d, ³J_H,H

Borane Adduct of (1R,3S)-3-Ethoxy-1-phenyl-2-[(R)-1-phenylethyl]-

2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-

21b·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and ethanol (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 784.6 mg

(1.78 mmol, 89%). [α]²_D⁷= –181.8 (c = 0.5, CH₂Cl₂). ¹H NMR

3

(400 MHz, CDCl₃): δ = 0.96 (t, J_H,H= 7.0 Hz, 3 H, CH₃), 1.85

(d, ³J_H,H= 7.1 Hz, 3 H, CH₃), 3.65 (m, 1 H, OCH₂), 3.93 (m, 1 H,

3

OCH₂), 5.39 (dq, J_H,H= 7.1, J_H,P= 12.1 Hz, 1 H, CH), 5.70 (d,

³J_H,P= 15.3 Hz, 1 H, CH), 6.72–6.89 (m, 3 H, Ar), 7.04–7.31 (m,

11 H, Ar), 7.63–7.72 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 15.8 (d, J = 7.1 Hz, CH₃), 20.2 (d, J = 3.5 Hz, CH₃),

53.6 (d, J = 4.0 Hz, CH), 55.3 (d, J = 15.8 Hz, CH), 62.6 (d, J =

2.1 Hz, OCH₂), 119.4 (d, J = 6.7 Hz, CH, Ar), 120.5 (d, J = 8.3 Hz,

C_q, Ar), 121.8 (CH, Ar), 124.4 (CH, Ar), 126.6 (CH, Ar), 127.3

(CH, Ar), 127.5 (3ϫCH, Ar),127.9 (2ϫCH, Ar), 128.2 (2ϫCH,

Ar), 128.3 (3ϫCH, Ar), 129.6 (CH, Ar), 129.96 (C_q, Ar), 130.03

(C_q, Ar), 139.1 (d, J = 4.6 Hz, C_q, Ar), 140.9 (C_q, Ar), 147.6 (d, J

= 9.6 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

115.8 ppm.

= 7.0 Hz, 3 H, CH₃), 4.62 (dq, J_H,H= 7.0, J_H,P= 20.6 Hz, 1 H,

CH), 5.90 (s, 1 H, CH), 7.13–7.49 (m, 13 H, Ar), 7.72–7.80 (m, 2

H, Ar), 7.87 (m, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃):

δ = 17.5 (d, J = 9.5 Hz, CH₃), 56.4 (d, J = 26.0 Hz, CH), 57.6 (d,

J = 7.0 Hz, CH), 120.1 (d, J = 8.3 Hz, C_q, Ar), 120.5 (d, J = 1.3 Hz,

CH, Ar), 122.1 (CH, Ar), 124.7 (CH, Ar), 126.8 (CH, Ar), 127.9

(CH, Ar), 128.0 (CH, Ar), 128.1 (CH, Ar), 128.2 (CH, Ar), 128.5

(2ϫCH, Ar), 128.6 (2ϫCH, Ar), 128.7 (2ϫCH, Ar), 129.0 (CH,

Ar), 129.7 (CH, Ar), 130.3 (C_q, Ar), 131.3 (C_q, Ar), 139.7 (d, J =

6.3 Hz, C_q, Ar), 142.0 (d, J = 2.9 Hz, C_q, Ar), 145.5 (d, J = 3.8 Hz,

C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 140.1 ppm.

Borane Adduct of (1R,3S)-3-Methoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)- Borane Adduct of (1R,3R)-3-Ethoxy-1-phenyl-2-[(R)-1-phenylethyl]-

21a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and methanol (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 717.8 mg

(1.68 mmol, 84%). ¹H NMR (400 MHz, CDCl₃): δ = 1.85 (d, ³J_H,H

2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-

21b·BH₃]: The compound was synthesized by following the general

procedure GP-Syn2 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(3.0 mmol, 1.0 equiv.) and ethanol (3.6 mmol, 1.2 equiv.). The

product was obtained as a colorless solid, yield 503.1 mg

(1.14 mmol, 38%). [α]²_D⁷= –110.9 (c = 0.5, CH₂Cl₂). ¹H NMR

3

= 7.1 Hz, 3 H, CH₃), 3.35 (d, J_H,H= 11.9 Hz, 3 H, OCH₃), 5.38

3

(dq, J_H,H= 6.9, J_H,P= 12.2 Hz, 1 H, CH), 5.69 (d, J_H,P

=

(400 MHz, CDCl₃): δ = 1.24 (t, J_H,H= 7.3 Hz, 3 H, CH₃), 1.37

15.0 Hz, 1 H, CH), 6.79 (t, ³J_H,H= 7.2 Hz, 1 H, Ar), 6.87 (m, 2 H,

(d, J_H,H= 7.1 Hz, 3 H, CH₃), 4.05–4.21 (m, 2 H, OCH₂), 5.07

3

Ar), 7.08 (d, J_H,H= 8.5 Hz, 1 H, Ar), 7.15–7.29 (m, 10 H, Ar), (dq, ³J_H,H= 7.0, ³J_H,P= 11.8 Hz, 1 H, CH), 5.64 (d, ³J_H,P= 9.3 Hz,

3

7.69 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

20.2 (d, J = 3.7 Hz, CH₃), 52.8 (d, J = 2.4 Hz, OCH₃), 53.7 (d, J

1 H, CH), 7.01–7.44 (m, 11 H, Ar), 7.52 (m, 3 H, Ar), 7.69–7.77

(m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 16.4 (d,

= 3.8 Hz, CH), 55.4 (d, J = 15.3 Hz, CH), 119.3 (d, J = 6.6 Hz, J = 4.8 Hz, CH₃), 19.2 (d, J = 4.0 Hz, CH₃), 54.0 (d, J = 1.8 Hz,

Eur. J. Org. Chem. 2015, 6205–6230

www.eurjoc.org

6219

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

3

CH), 55.1 (d, J = 12.5 Hz, CH), 63.8 (d, J = 3.1 Hz, OCH₂), 119.4 7.1 Hz, 3 H, CH₃), 5.47 (dq, J_H,H= 7.0, J_H,P= 11.7 Hz, 1 H,

3

(d, J = 2.8 Hz, CH, Ar), 121.7 (CH, Ar), 124.7 (d, J = 11.4 Hz,

CH), 5.66 (d, J_H,P= 16.2 Hz, 1 H, CH), 6.77–6.91 (m, 3 H, Ar),

3

C_q, Ar), 125.0 (CH, Ar), 127.0 (3ϫCH, Ar), 127.5 (CH, Ar), 127.6 7.04–7.34 (m, 11 H, Ar), 7.70 (d, J_H,H= 8.6 Hz, 2 H, Ar) ppm.

(CH, Ar), 128.0 (2 ϫ CH, Ar), 128.58 (2 ϫ CH, Ar), 128.61 ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.8 (d, J = 2.2 Hz, CH₃),

(2ϫCH, Ar), 128.9 (CH, Ar), 129.4 (C_q, Ar), 129.8 (CH, Ar), 131.1

(C_q, Ar), 139.7 (d, J = 2.5 Hz, C_q, Ar), 143.6 (C_q, Ar), 144.1 (d, J

30.1 (d, J = 2.9 Hz, 3ϫCH₃), 53.9 (d, J = 4.4 Hz, CH), 54.8 (d, J

= 16.1 Hz, CH), 83.7 (d, J = 6.3 Hz, OC_q), 119.6 (d, J = 6.7 Hz,

= 10.4 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = CH, Ar), 121.6 (d, J = 7.4 Hz, C_q, Ar), 121.8 (CH, Ar), 124.3 (CH,

108.5 ppm.

Ar), 126.5 (CH, Ar), 127.1 (CH, Ar), 127.2 (CH, Ar), 127.7

(2ϫCH, Ar), 127.8 (2ϫCH, Ar), 128.0 (2ϫCH, Ar), 128.2 (CH,

Ar), 128.5 (2ϫCH, Ar), 129.4 (CH, Ar), 129.9 (C_q, Ar), 130.1 (C_q,

Ar), 139.4 (d, J = 5.8 Hz, C_q, Ar), 141.3 (C_q, Ar), 147.6 (d, J =

9.0 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

108.6 ppm.

Borane Adduct of (1R,3S)-3-Isopropoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-

21c·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and isopropanol (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 728.5 mg

(1.60 mmol, 80%). [α]²_D⁷= –157.3 (c = 0.5, CH₂Cl₂). ¹H NMR

Borane Adduct of (1R,3R)-3-(tert-Butoxy)-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-

21d·BH₃]: The compound was synthesized by following the general

procedure GP-Syn2 for ligand synthesis starting from 1-((R)-

3

(400 MHz, CDCl₃): δ = 1.11 (d, J_H,H= 6.7 Hz, 3 H, CH₃), 1.13

(d, ³J_H,H= 6.6 Hz, 3 H, CH₃), 1.76 (d, J_H,H= 7.1 Hz, 3 H, CH₃), phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

3

4.69 (dsept, J_H,H= 6.2, J_H,P= 14.2 Hz, 1 H, OCH), 5.40 (dq,

(3.0 mmol, 1.0 equiv.) and tert-butanol (3.0 mmol, 1.0 equiv.). The

³J_H,H= 7.0, J_H,P= 11.6 Hz, 1 H, CH), 5.67 (d, J_H,P= 16.4 Hz, product was obtained as a colorless solid, yield 484.4 mg

3

1 H, CH), 6.82–6.96 (m, 3 H, Ar), 7.06–7.37 (m, 11 H, Ar), 7.64– (1.03 mmol, 34%). [α]²_D⁷= –125.8 (c = 0.5, CH₂Cl₂). ¹H NMR

7.73 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

(400 MHz, CDCl₃): δ = 1.30 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.38

3

19.9 (d, J = 2.5 Hz, CH₃), 23.7 (d, J = 5.1 Hz, CH₃), 23.8 (d, J = (s, 9 H, 3 CH₃), 5.00 (dq, J_H,H= 6.9, J_H,P= 12.0 Hz, 1 H, CH),

3

3.0 Hz, CH₃), 54.2 (d, J = 4.5 Hz, CH), 55.1 (d, J = 15.4 Hz, CH), 5.55 (d, J_H,P= 8.7 Hz, 1 H, CH), 7.01–7.38 (m, 11 H, Ar), 7.43–

72.4 (d, J = 2.2 Hz, OCH), 119.4 (d, J = 6.6 Hz, CH, Ar), 121.75 7.49 (m, 3 H, Ar), 7.62–7.72 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR

(CH, Ar), 121.84 (d, J = 7.4 Hz, C_q, Ar), 124.4 (CH, Ar), 126.6

(CH, Ar), 127.3 (CH, Ar), 127.4 (CH, Ar), 127.7 (2ϫCH, Ar),

128.0 (2 ϫ CH, Ar), 128.1 (2 ϫ CH, Ar), 128.3 (CH, Ar), 128.5

(2ϫCH, Ar), 129.5 (CH, Ar), 129.9 (C_q, Ar), 130.1 (C_q, Ar), 139.2

(100 MHz, CDCl₃): δ = 19.3 (d, J = 5.3 Hz, CH₃), 30.1 (d, J =

2.8 Hz, 3ϫCH₃), 54.0 (d, J = 2.3 Hz, CH), 54.9 (d, J = 11.5 Hz,

CH), 82.9 (d, J = 6.9 Hz, OC_q), 119.6 (d, J = 3.3 Hz, CH, Ar),

121.9 (CH, Ar), 124.7 (d, J = 12.1 Hz, C_q, Ar), 124.9 (CH, Ar),

(d, J = 5.2 Hz, C_q, Ar), 141.2 (C_q, Ar), 147.4 (d, J = 8.8 Hz, C_q, 127.0 (CH, Ar), 127.2 (2ϫCH, Ar), 127.4 (CH, Ar), 127.5 (CH,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 114.1 ppm.

Ar), 128.0 (2ϫCH, Ar), 128.50 (2ϫCH, Ar), 128.54 (2ϫCH, Ar),

128.9 (CH, Ar), 129.5 (C_q, Ar), 129.6 (CH, Ar), 131.1 (C_q, Ar),

140.3 (d, J = 1.9 Hz, C_q, Ar), 144.0 (d, J = 10.3 Hz, C_q, Ar), 144.1

(C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 100.8 ppm.

Borane Adduct of (1R,3R)-3-Isopropoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-

21c·BH₃]: The compound was synthesized by following the general

procedure GP-Syn2 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(3.0 mmol, 1.0 equiv.) and isopropanol (3.6 mmol, 1.2 equiv.). The

product was obtained as a colorless solid, yield 290.0 mg

Borane Adduct of (1R,3S)-3-Phenoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-

21e·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and phenol (2.0 mmol, 1.0 equiv.). The prod-

uct was obtained as a colorless solid, yield 801.6 mg (1.64 mmol,

82%). [α]²_D⁷= –154.4 (c = 0.5, CH₂Cl₂). ¹H NMR (400 MHz,

(0.64 mmol, 21%). [α]²_D⁷= –128.2 (c = 0.5, CH₂Cl₂). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.24 (m, 6 H, 2 CH₃), 1.38 (d, J_H,H

=

3

7.1 Hz, 3 H, CH₃), 4.85 (dsept, J_H,H= 6.2, J_H,P= 13.9 Hz, 1 H,

3

OCH), 5.03 (dq, J_H,H= 7.0, J_H,P= 11.8 Hz, 1 H, CH), 5.61 (d,

³J_H,P= 9.5 Hz, 1 H, CH), 7.06–7.56 (m, 14 H, Ar), 7.66–7.77 (m,

CDCl₃): δ = 1.84 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 5.50 (dq, J_H,H

=

3

2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.1 (d, J 6.9, ³J_H,P= 12.0 Hz, 1 H, CH), 5.77 (d, ³J_H,P= 15.6 Hz, 1 H, CH),

= 4.1 Hz, CH₃), 23.6 (d, J = 5.9 Hz, CH₃), 23.8 (d, J = 1.3 Hz, 6.81–6.95 (m, 5 H, Ar), 7.05–7.40 (m, 14 H, Ar), 7.66–7.77 (m, 2

CH₃), 53.9 (d, J = 1.3 Hz, CH), 54.9 (d, J = 12.2 Hz, CH), 72.4

(d, J = 2.5 Hz, OCH), 119.5 (d, J = 3.3 Hz, CH, Ar), 121.7 (CH, 2.6 Hz, CH₃), 54.4 (d, J = 4.3 Hz, CH), 55.8 (d, J = 16.1 Hz, CH),

H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 20.1 (d, J =

Ar), 124.7 (d, J = 11.5 Hz, C_q, Ar), 124.8 (CH, Ar), 126.97 (CH,

Ar), 127.04 (2ϫCH, Ar), 127.4 (CH, Ar), 127.6 (CH, Ar), 127.9

119.3 (d, J = 6.6 Hz, CH, Ar), 121.1 (d, J = 3.8 Hz, 2ϫCH, Ar),

121.4 (d, J = 7.6 Hz, C_q, Ar), 121.7 (CH, Ar), 124.7 (CH, Ar),

(2 ϫ CH, Ar), 128.53 (2 ϫ CH, Ar), 128.56 (2 ϫ CH, Ar), 128.8 124.8 (CH, Ar), 126.8 (CH, Ar), 127.5 (CH, Ar), 127.6 (2ϫCH,

(CH, Ar), 129.4 (C_q, Ar), 129.7 (CH, Ar), 131.0 (C_q, Ar), 139.8 (d, Ar), 127.8 (CH, Ar), 128.1 (2ϫCH, Ar), 128.4 (3ϫCH, Ar), 128.6

J = 4.6 Hz, C_q, Ar), 143.7 (C_q, Ar), 144.0 (d, J = 10.1 Hz, C_q,

(2ϫCH, Ar), 129.3 (2ϫCH, Ar), 129.82 (CH, Ar), 129.87 (C_q,

Ar), 130.2 (C_q, Ar), 138.8 (d, J = 5.6 Hz, C_q, Ar), 140.3 (C_q, Ar),

147.2 (d, J = 9.1 Hz, C_q, Ar), 150.7 (d, J = 4.1 Hz, OC_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 114.3 ppm.

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 107.1 ppm.

Borane Adduct of (1R,3S)-3-(tert-Butoxy)-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-

21d·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and tert-butanol (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 694.6 mg

Borane Adduct of (1R,3S)-3-(Naphthalen-1-yloxy)-1-phenyl-2-[(R)-

1-phenylethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphos-

phinine [(S_P)-21f·BH₃]: The compound was synthesized by follow-

ing the general procedure GP-Syn1 for ligand synthesis starting

from 1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-

2-ol (1.0 mmol, 1.0 equiv.) and 1-naphthol (1.0 mmol, 1.0 equiv.).

The product was obtained as a colorless solid, yield 447.7 mg

(1.48 mmol, 74%). [α]²_D⁷= –124.0 (c = 0.5, CH₂Cl₂). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.33 (s, 9 H, 3 CH₃), 1.79 (d, J_H,H

=

6220

www.eurjoc.org

Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

(0.83 mmol, 83%). ¹H NMR (400 MHz, CDCl₃): δ = 1.97 (d, ³J_H,H

Ar), 127.4 (CH, Ar), 127.6 (2ϫCH, Ar), 127.8 (CH, Ar), 128.0

(2ϫCH, Ar), 128.14 (2ϫCH, Ar), 128.26 (2ϫCH, Ar), 128.29

(CH, Ar), 128.5 (2ϫCH, Ar), 129.5 (CH, Ar), 129.8 (C_q, Ar), 130.1

(C_q, Ar), 139.1 (d, J_C,P= 6.0 Hz, C_q, Ar), 141.1 (C_q, Ar), 142.2 (d,

J_C,P= 5.4 Hz, C_q, Ar), 147.2 (d, J_C,P= 8.7 Hz, C_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 116.0 ppm.

3

= 7.1 Hz, 3 H, CH₃), 5.64 (dq, J_H,H= 6.9, J_H,P= 11.9 Hz, 1 H,

3

CH), 5.84 (d, J_H,P= 16.1 Hz, 1 H, CH), 6.87 (m, 1 H, Ar), 6.93

(m, 2 H, Ar), 7.00 (m, 1 H, Ar), 7.05 (m, 2 H, Ar), 7.12 (m, 1 H,

Ar), 7.17 (m, 1 H, Ar), 7.27 (m, 1 H, Ar), 7.30–7.40 (m, 8 H, Ar),

3

7.42 (m, 1 H, Ar), 7.60 (d, J_H,H= 7.8 Hz, 1 H, Ar), 7.69 (d, J_H,H

= 8.2 Hz, 2 H, Ar), 7.75 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃): δ = 20.3 (d, J_C,P= 2.4 Hz, CH₃), 54.5 (d, J_C,P

Borane Adduct of (1R,3S)-1-Phenyl-3-[(S)-1-phenylethoxy]-2-[(R)-1-

phenylethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine

[(S_P)-21i·BH₃]: The compound was synthesized by following the

general procedure GP-Syn1 for ligand synthesis starting from 1-

((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(1.0 mmol, 1.0 equiv.) and (S)-1-phenylethanol (1.0 mmol,

1.0 equiv.). The product was obtained as a colorless solid, yield

368.9 mg (0.71 mmol, 71%). ¹H NMR (400 MHz, CDCl₃): δ = 1.46

= 4.3 Hz, CH), 55.7 (d, J_C,P= 16.1 Hz, CH), 115.5 (d, J_C,P

=

3.9 Hz, CH, Ar), 119.2 (d, J_C,P= 6.7 Hz, CH, Ar), 121.71 (CH,

Ar), 121.74 (d, J_C,P= 5.7 Hz, C_q, Ar), 122.3 (CH, Ar), 124.6 (CH,

Ar), 124.7 (CH, Ar), 125.2 (CH, Ar), 125.8 (CH, Ar), 126.4 (CH,

Ar), 126.73 (d, J_C,P= 4.6 Hz, C_q, Ar), 126.76 (CH, Ar), 127.45

(CH, Ar), 127.51 (CH, Ar), 127.58 (CH, Ar), 127.63 (2ϫCH, Ar),

128.1 (2 ϫ CH, Ar), 128.27 (2 ϫ CH, Ar), 128.30 (2 ϫ CH, Ar),

128.35 (CH, Ar), 129.8 (CH, Ar), 129.9 (C_q, Ar), 130.2 (C_q, Ar),

134.6 (C_q, Ar), 138.7 (d, J_C,P= 5.7 Hz, C_q, Ar), 140.2 (C_q, Ar),

147.1 (d, J_C,P= 10.0 Hz, C_q, Ar), 147.2 (d, J_C,P= 4.8 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 115.3 ppm.

3

(d, ³J_H,H= 6.4 Hz, 3 H, CH₃), 1.77 (d, J_H,H= 7.0 Hz, 3 H, CH₃),

3

5.44 (dq, J_H,H= 6.9, J_H,P= 11.5 Hz, 1 H, CH), 5.59 (dq, J_H,H

3

= 6.5, J_H,P= 8.4 Hz, 1 H, CH), 5.67 (d, J_H,P= 16.7 Hz, 1 H,

CH), 6.86 (m, 3 H, Ar), 7.05–7.34 (m, 16 H, Ar), 7.64 (d, J_H,H

3

=

3

8.9 Hz, 1 H, Ar), 7.65 (d, J_H,H= 7.9 Hz, 1 H, Ar) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃): δ = 19.9 (d, J_C,P= 1.5 Hz, CH₃), 24.7

(d, J_C,P= 4.2 Hz, CH₃), 54.3 (d, J_C,P= 3.9 Hz, CH), 55.1 (d, J_C,P

= 15.7 Hz, CH), 77.0 (CH), 119.4 (d, J_C,P= 6.5 Hz, CH, Ar), 121.6

(CH, Ar), 121.7 (d, J_C,P= 7.2 Hz, C_q, Ar), 124.4 (CH, Ar), 125.8

(2ϫCH, Ar), 126.5 (CH, Ar), 127.3 (CH, Ar), 127.4 (CH, Ar),

127.6 (2ϫ, CH, Ar), 127.7 (CH, Ar), 128.0 (2ϫCH, Ar), 128.2

(4ϫCH, Ar), 128.3 (CH, Ar), 128.5 (2ϫCH, Ar), 129.4 (CH, Ar),

129.7 (C_q, Ar), 130.0 (C_q, Ar), 139.0 (d, J_C,P= 5.8 Hz, C_q, Ar),

141.2 (C_q, Ar), 141.9 (d, J_C,P= 3.7 Hz, C_q, Ar), 147.1 (d, J_C,P

= 8.8 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

115.0 ppm.

Borane Adduct of (1R,3S)-3-(Naphthalen-2-yloxy)-1-phenyl-2-[(R)-

1-phenylethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphin-

ine [(S_P)-21g·BH₃]: The compound was synthesized by following

the general procedure GP-Syn1 for ligand synthesis starting from

1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(1.0 mmol, 1.0 equiv.) and 2-naphthol (1.0 mmol, 1.0 equiv.).

The product was obtained as a colorless solid, yield 431.0 mg

(0.80 mmol, 80%). ¹H NMR (400 MHz, CDCl₃): δ = 1.84 (d, ³J_H,H

3

= 7.0 Hz, 3 H, CH₃), 5.52 (dq, J_H,H= 6.9, J_H,P= 12.1 Hz, 1 H,

3

CH), 5.79 (d, J_H,P= 15.5 Hz, 1 H, CH), 6.83 (m, 1 H, Ar), 6.90

3

4

(m, 2 H, Ar), 6.99 (dd, J_H,H= 8.9, J_H,H= 1.8 Hz, 1 H, Ar), 7.09

(m, 1 H, Ar), 7.13–7.21 (m, 5 H, Ar), 7.23–7.31 (m, 3 H, Ar), 7.34

(d, ³J_H,H= 8.9 Hz, 1 H, Ar), 7.36–7.45 (m, 4 H, Ar), 7.67 (m, 3 H,

Ar), 7.74 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ

= 20.1 (d, J_C,P= 2.6 Hz, CH₃), 54.3 (d, J_C,P= 4.4 Hz, CH), 55.8

(d, J_C,P= 16.2 Hz, CH), 117.5 (d, J_C,P= 4.3 Hz, CH, Ar), 119.2

(d, J_C,P= 6.9 Hz, CH, Ar), 121.1 (d, J_C,P= 3.2 Hz, CH, Ar), 121.2

(d, J_C,P= 7.2 Hz, C_q, Ar), 121.6 (CH, Ar), 124.6 (CH, Ar), 125.3

(CH, Ar), 126.4 (CH, Ar), 126.7 (CH, Ar), 127.43 (CH, Ar), 127.46

(CH, Ar), 127.55 (2ϫCH, Ar), 127.62 (CH, Ar), 127.8 (CH, Ar),

128.0 (2 ϫ CH, Ar), 128.3 (CH, Ar), 128.4 (2ϫ CH, Ar), 128.7

(2ϫCH, Ar), 129.2 (CH, Ar), 129.79 (CH, Ar), 129.80 (C_q, Ar),

(1R,3S)-3-Methoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21a]: The compound

was synthesized from the borane adduct (1.0 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 401.0 mg

(0.97 mmol, 97%). [α]²_D⁵= –98.0 (c = 0.5, CH₂Cl₂). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.73 (d, J_H,H= 6.9 Hz, 3 H, CH₃), 2.86

3

(d, J_H,P= 13.1 Hz, 3 H, OCH₃), 4.81 (dq, d, J_H,H= 7.0, J_H,P

=

3

11.4 Hz, 1 H, CH), 5.62 (d, J_H,P= 5.2 Hz, 1 H, CH), 6.82 (m, 1

H, Ar), 6.90 (m, 2 H, Ar), 7.02–7.21 (m, 11 H, Ar), 7.59 (m, 2 H,

Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 21.4 (d, J =

11.7 Hz, CH₃), 49.3 (d, J = 16.0 Hz, OCH₃), 54.1 (d, J = 3.3 Hz,

CH), 58.8 (d, J = 37.3 Hz, CH), 118.2 (d, J = 8.0 Hz, C_q, Ar),

120.7 (d, J = 2.9 Hz, CH, Ar), 122.0 (CH, Ar), 123.5 (CH, Ar),

126.3 (CH, Ar), 126.7 (CH, Ar), 127.1 (CH, Ar), 127.3 (2ϫCH,

Ar), 127.8 (2ϫCH, Ar), 128.0 (2ϫCH, Ar), 128.3 (CH, Ar), 128.4

(2ϫCH, Ar), 128.9 (CH, Ar), 129.5 (C_q, Ar), 131.3 (C_q, Ar), 141.8

(d, J = 4.5 Hz, C_q, Ar), 142.8 (C_q, Ar), 148.4 (d, J = 8.0 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 136.6 ppm. MS

(EI): m/z (%) = 279.2 (19), 167.1 (34), 149.1 (100), 71.3 (13). HRMS

(ESI): m/z calcd. for C₂₆H₂₄NO₂P⁺[M⁺] 413.15392; found

413.15411.

130.1 (C_q, Ar), 130.8 (C_q, Ar), 133.7 (C_q, Ar), 138.7 (d, J_C,P

=

5.5 Hz, C_q, Ar), 140.2 (C_q, Ar), 147.2 (d, J_C,P= 9.2 Hz, C_q, Ar),

148.2 (d, J_C,P= 4.5 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz,

CDCl₃): δ = 114.5 ppm.

Borane Adduct of (1R,3S)-1-Phenyl-3-[(R)-1-phenylethoxy]-2-

[(R)-1-phenylethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphos-

phinine [(S_P)-21h·BH₃]: The compound was synthesized by follow-

ing the general procedure GP-Syn1 for ligand synthesis starting

from 1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-

2-ol (1.0 mmol, 1.0 equiv.) and (R)-1-phenylethanol (1.0 mmol,

1.0 equiv.). The product was obtained as a colorless solid, yield

403.1 mg (0.78 mmol, 78%). ¹H NMR (400 MHz, CDCl₃): δ = 1.36

3

(d, J_H,H= 7.0 Hz, 3 H, CH₃), 1.40 (d, J_H,H= 6.5 Hz, 3 H, CH₃), (1R,3R)-3-Methoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

3

5.16 (dq, J_H,H= 7.0, J_H,P= 11.5 Hz, 1 H, CH), 5.55 (m, 2 H, naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-21a]: The compound

CH), 6.81 (m, 3 H, Ar), 7.01 (m, 3 H, Ar), 7.07 (m, 1 H, Ar), 7.11– was synthesized from the borane adduct (0.7 mmol) by following

7.20 (m, 9 H, Ar), 7.23 (d, J_H,H= 8.9 Hz, 1 H, Ar), 7.27 (m, 2 H, the general procedure GP-Syn4 for deprotection of ligands. The

3

Ar), 7.60 (d, J_H,H= 8.5 Hz, 1 H, Ar), 7.63 (d, J_H,H= 9.0 Hz, 1

product was obtained as a colorless solid, yield 248.9 mg

H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.5 (d, J_C,P(0.60 mmol, 86%). ¹H NMR (400 MHz, CDCl₃): δ = 1.53 (d, ³J_H,H

3

= 1.2 Hz, CH₃), 24.8 (d, J_C,P= 2.9 Hz, CH₃), 54.3 (d, J_C,P= 4.0 Hz,

CH), 55.0 (d, J_C,P= 16.1 Hz, CH), 77.1 (CH), 119.3 (d, J_C,P

= 6.8 Hz, 3 H, CH₃), 3.30 (d, J_H,P= 11.9 Hz, 3 H, OCH₃), 4.55

3

=

(dq, J_H,H= 7.2, J_H,P= 15.7 Hz, 1 H, CH), 5.81 (s 1 H, CH),

6.4 Hz, CH, Ar), 121.6 (CH, Ar), 122.4 (d, J_C,P= 6.8 Hz, C_q, Ar),

124.4 (CH, Ar), 125.8 (2ϫCH, Ar), 126.6 (CH, Ar), 127.3 (CH,

7.09–7.33 (m, 10 H, Ar), 7.38 (m, 1 H, Ar), 7.48 (m, 2 H, Ar), 7.68

(d, J_H,H= 8.9 Hz, 1 H, Ar), 7.73 (d, J_H,H= 7.8 Hz, 1 H, Ar),

3

Eur. J. Org. Chem. 2015, 6205–6230

www.eurjoc.org

6221

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

7.86 (d, J_H,H= 8.7 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, The product was obtained as a colorless solid, yield 225.2 mg

3

CDCl₃): δ = 19.7 (d, J = 7.8 Hz, CH₃), 50.5 (d, J = 13.6 Hz, (0.51 mmol, 85%). ¹H NMR (400 MHz, CDCl₃): δ = 0.77 (d, ³J_H,H

3

OCH₃), 55.6 (d, J = 28.3 Hz, CH), 56.5 (d, J = 5.6 Hz, CH), 120.7 = 6.2 Hz, 3 H, CH₃), 1.03 (d, J_H,H= 6.1 Hz, 3 H, CH₃), 1.79 (d,

3

(CH, Ar), 122.0 (CH, Ar), 122.4 (d, J = 8.2 Hz, C_q, Ar), 124.0

(CH, Ar), 126.4 (CH, Ar), 127.1 (CH, Ar), 127.2 (CH, Ar), 128.0 12.3 Hz, 1 H, OCH), 4.87 (dq, J_H,H= 7.0, J_H,P= 11.7 Hz, 1 H,

³J_H,H= 7.1 Hz, 3 H, CH₃), 4.00 (dsept, J_H,H= 6.2, J_H,P

=

3

(2ϫCH, Ar), 128.2 (2ϫCH, Ar), 128.3 (4ϫCH, Ar), 128.8 (CH,

Ar), 129.3 (CH, Ar), 130.3 (C_q, Ar), 130.7 (C_q, Ar), 141.6 (d, J = 7.10–7.31 (m, 11 H, Ar), 7.62–7.71 (m, 2 H, Ar) ppm. ¹³C{¹H}

4.5 Hz, C_q, Ar), 144.0 (d, J = 2.0 Hz, C_q, Ar), 144.8 (d, J = 3.3 Hz, NMR (100 MHz, CDCl₃): δ = 21.3 (d, J = 12.0 Hz, CH₃), 23.8 (d,

C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 120.1 ppm. J = 4.5 Hz, CH₃), 24.1 (d, J = 4.4 Hz, CH₃), 54.5 (d, J = 3.6 Hz,

CH), 5.71 (d, J_H,P= 5.5 Hz, 1 H, CH), 6.87–7.02 (m, 3 H, Ar),

MS (EI): m/z (%) = 308.1 (14), 279.2 (18), 167.1 (33), 149.1 (100),

144.1 (68), 115.2 (31), 106.2 (16), 105.2 (15), 91.2 (11), 73.3 (36),

72.3 (26), 71.3 (13). HRMS (ESI): m/z calcd. for C₂₆H₂₄NO₂P⁺

[M⁺] 413.15392; found 413.15399.

CH), 58.8 (d, J = 38.9 Hz, CH), 67.5 (d, J = 19.8 Hz, OCH), 118.6

(d, J = 7.8 Hz, C_q, Ar), 120.8 (d, J = 2.9 Hz, CH, Ar), 122.0 (CH,

Ar), 123.3 (CH, Ar), 126.1 (CH, Ar), 126.5 (CH, Ar), 126.9 (CH,

Ar), 127.25 (CH, Ar), 127.28 (CH, Ar), 127.6 (2ϫCH, Ar), 127.8

(2ϫCH, Ar), 128.2 (CH, Ar), 128.7 (CH, Ar), 128.8 (2ϫCH, Ar),

129.4 (C_q, Ar), 131.3 (C_q, Ar), 142.0 (d, J = 5.0 Hz, C_q, Ar), 142.7

(C_q, Ar), 148.5 (d, J = 8.3 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR

(162 MHz, CDCl₃): δ = 134.8 ppm. MS (EI): m/z (%) = 279.3 (17),

167.2 (34), 149.1 (100), 71.3 (13), 70.3 (15). HRMS (ESI): m/z

calcd. for C₂₈H₂₈NO₂P⁺[M⁺] 441.18522; found 441.18568,

(1R,3S)-3-Ethoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21b]: The compound

was synthesized from the borane adduct (0.7 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 278.3 mg

(0.65 mmol, 93%). ¹H NMR (400 MHz, CDCl₃): δ = 0.83 (t, ³J_H,H

3

(1R,3R)-3-Isopropoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-21c]: The com-

pound was synthesized from the borane adduct (0.42 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 168.7 mg

(0.38 mmol, 91%). ¹H NMR (400 MHz, CDCl₃): δ = 0.98 (d, ³J_H,H

= 7.0 Hz, 3 H, CH₃), 1.81 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 3.14 (m,

3

1 H, OCH₂), 3.51 (m, 1 H, OCH₂), 4.87 (dq, J_H,H= 7.0, J_H,P

=

3

11.3 Hz, 1 H, CH), 5.70 (d, J_H,P= 5.3 Hz, 1 H, CH), 6.90 (m, 1

H, Ar), 6.97 (m, 2 H, Ar), 7.09–7.30 (m, 11 H, Ar), 7.62–7.71 (m,

2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 16.3 (d, J

= 7.3 Hz, CH₃), 21.3 (d, J = 12.4 Hz, CH₃), 54.0 (d, J = 3.8 Hz,

CH), 58.5 (d, J = 18.4 Hz, OCH₂), 58.7 (d, J = 37.6 Hz, CH), 118.2

(d, J = 8.3 Hz, C_q, Ar), 120.7 (d, J = 3.7 Hz, CH, Ar), 122.0 (CH,

Ar), 123.4 (CH, Ar), 126.2 (CH, Ar), 127.0 (CH, Ar), 127.2

(2 ϫ CH, Ar), 127.7 (2 ϫ CH, Ar), 127.9 (2 ϫ CH, Ar), 128.2

(2ϫCH, Ar), 128.4 (2ϫCH, Ar), 128.8 (CH, Ar), 129.4 (C_q, Ar),

131.3 (C_q, Ar), 141.8 (d, J = 4.3 Hz, C_q, Ar), 142.7 (C_q, Ar), 148.5

(d, J = 8.5 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ

= 135.3 ppm. MS (EI): m/z (%) = 279.3 (20), 167.1 (35), 150.1 (10),

149.1 (100), 144.2 (24), 115.2 (11), 113.3 (10), 106.2 (10), 86.2 (35),

85.2 (11), 72.3 (10), 71.3 (17), 70.3 (29). HRMS (ESI): m/z calcd.

for C₂₇H₂₆NO₂P⁺[M⁺] 427.16957; found 427.16934.

3

= 6.2 Hz, 3 H, CH₃), 1.14 (d, J_H,H= 6.2 Hz, 3 H, CH₃), 1.53 (d,

³J_H,H= 6.9 Hz, 3 H, CH₃), 4.26 (dsept, ³J_H,H= 6.2, ³J_H,P= 9.3 Hz,

3

1 H, OCH), 4.53 (dq, J_H,H= 7.1, ³J_H,P= 16.2 Hz, 1 H, CH), 5.79

(s, 1 H, CH), 7.07–7.26 (m, 9 H, Ar), 7.30 (m, 1 H, Ar), 7.37 (m,

1 H, Ar), 7.48 (m, 2 H, Ar), 7.67 (d, ³J_H,H= 8.9 Hz, 1 H, Ar), 7.73

(d, ³J_H,H= 8.2 Hz, 1 H, Ar), 7.84 (d, ³J_H,H= 8.4 Hz, 1 H, Ar) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.3 (d, J = 7.7 Hz, CH₃),

24.3 (d, J = 2.0 Hz, CH₃), 24.6 (d, J = 5.5 Hz, CH₃), 55.5 (d, J =

28.4 Hz, CH), 56.4 (d, J = 5.5 Hz, CH), 67.2 (d, J = 20.6 Hz,

OCH), 121.2 (CH, Ar), 122.1 (CH, Ar), 122.7 (d, J = 8.4 Hz, C_q,

Ar), 123.8 (CH, Ar), 126.2 (CH, Ar), 127.0 (CH, Ar), 127.1 (CH,

Ar), 128.01 (CH, Ar), 128.03 (CH, Ar), 128.06 (2 ϫ CH, Ar),

128.25 (2ϫCH, Ar), 128.33 (2ϫCH, Ar), 128.7 (CH, Ar), 128.9

(CH, Ar), 130.4 (C_q, Ar), 130.5 (C_q, Ar), 142.1 (d, J = 7.2 Hz, C_q,

Ar), 143.0 (d, J = 2.2 Hz, C_q, Ar), 144.3 (d, J = 3.1 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 119.5 ppm. MS

(EI): m/z (%) = 231.3 (19), 209.4 (25), 208.3 (31), 194.3 (17), 167.3

(19), 149.2 (50), 144.3 (85), 116.3 (12), 115.3 (42), 109.2 (40), 106.3

(23), 105.3 (100), 104.3 (12), 89.3 (10), 83.2 (52), 79.3 (11), 77.3

(18). HRMS (ESI): m/z calcd. for C₂₈H₂₈NO₂P⁺[M⁺] 441.18522;

found 441.18549.

(1R,3R)-3-Ethoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-21b]: The compound

was synthesized from the borane adduct (0.5 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 188.1 mg

(0.44 mmol, 88%). ¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, ³J_H,H

3

= 6.8 Hz, 3 H, CH₃), 1.46 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 3.55 (m,

3

1 H, OCH₂), 3.67 (m, 1 H, OCH₂), 4.48 (dq, J_H,H= 7.1, J_H,P

=

15.9 Hz, 1 H, CH), 5.73 (s, 1 H, CH), 7.00–7.48 (m, 13 H, Ar),

3

7.59 (³J_H,H= 8.9 Hz, 1 H, Ar), 7.65 (d, J_H,H= 8.1 Hz, 1 H, Ar),

(1R,3S)-3-(tert-Butoxy)-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21d]: The com-

pound was synthesized from the borane adduct (0.7 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 312.5 mg

3

7.78 (d, J_H,H= 8.6 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 17.1 (d, J = 4.8 Hz, CH₃), 19.5 (d, J = 8.0 Hz, CH₃),

55.6 (d, J = 28.0 Hz, CH), 56.5 (d, J = 5.7 Hz, CH), 59.4 (d, J =

16.9 Hz, OCH₂), 120.9 (CH, Ar), 122.1 (CH, Ar), 122.5 (d, J =

8.1 Hz, C_q, Ar), 123.9 (CH, Ar), 126.3 (CH, Ar), 127.07 (CH, Ar),

127.12 (CH, Ar), 127.97 (CH, Ar), 128.00 (CH, Ar), 128.1 (2ϫCH,

Ar), 128.3 (4ϫCH, Ar), 128.7 (CH, Ar), 129.1 (CH, Ar), 130.3

(C_q, Ar), 130.6 (C_q, Ar), 141.8 (d, J = 4.2 Hz, C_q, Ar), 144.2 (d, J

= 2.1 Hz, C_q, Ar), 145.1 (d, J = 2.9 Hz, C_q, Ar) ppm. ³¹P{¹H}

NMR (162 MHz, CDCl₃): δ = 119.1 ppm. MS (EI): m/z (%) =

279.3 (18), 196.2 (10), 167.2 (33), 149.1 (100), 113.3 (10). HRMS

(ESI): m/z calcd. for C₂₇H₂₆NO₂P⁺[M⁺] 427.16957; 427.17011.

1

(0.69 mmol, 98%). H NMR (400 MHz, CDCl₃): δ = 1.33 (s, 9 H,

3

3 CH₃), 1.79 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 4.97 (dq, J_H,H= 6.9,

³J_H,P= 12.0 Hz, 1 H, CH), 5.79 (d, ³J_H,P= 5.9 Hz, 1 H, CH), 7.00–

7.12 (m, 3 H, Ar), 7.17–7.49 (m, 11 H, Ar), 7.66 (m, 2 H, Ar) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 20.1 (d, J = 20.9 Hz, CH₃),

30.1 (d, J = 2.9 Hz, 3ϫCH₃), 54.3 (d, J = 3.7 Hz, CH), 58.1 (d, J

= 38.1 Hz, CH), 83.0 (d, J = 20.1 Hz, OC_q), 117.9 (d, J = 7.4 Hz,

C_q, Ar), 119.6 (d, J = 6.7 Hz, CH, Ar), 121.8 (CH, Ar), 124.3 (CH,

Ar), 126.5 (CH, Ar), 127.1 (CH, Ar), 127.2 (CH, Ar), 127.7

(2ϫCH, Ar), 127.8 (2ϫCH, Ar), 128.0 (2ϫCH, Ar), 128.2 (CH,

Ar), 128.5 (2ϫCH, Ar), 129.4 (CH, Ar), 130.0 (C_q, Ar), 131.6 (C_q,

Ar), 139.4 (d, J = 5.8 Hz, C_q, Ar), 141.3 (C_q, Ar), 147.5 (d, J =

(1R,3S)-3-Isopropoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21c]: The com-

pound was synthesized from the borane adduct (0.6 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

6222

www.eurjoc.org

Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

9.0 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 5.9 Hz, 1 H, CH), 6.93–7.47 (m, 20 H, Ar), 7.69 (m, 3 H, Ar) ppm.

131.9 ppm. MS (EI): m/z (%) = 399.2 (27), 322.1 (17), 294.1 (37),

280.1 (11), 234.2 (13), 231.1 (26), 218.1 (60), 215.2 (10), 209.2 (22),

208.1 (11), 194.2 (15), 167.1 (14), 149.1 (35), 144.1 (51), 115.2 (24),

106.2 (29), 105.2 (100), 104.2 (13), 91.2 (14), 83.1 (19), 79.2 (14),

¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 21.6 (d, J_C,P= 11.1 Hz,

CH₃), 55.8 (d, J_C,P= 4.1 Hz, CH), 59.6 (d, J_C,P= 39.2 Hz, CH),

112.6 (d, J_C,P= 16.8 Hz, CH, Ar), 118.7 (d, J_C,P= 6.9 Hz, C_q, Ar),

120.4 (d, J_C,P= 3.6 Hz, CH, Ar), 122.1 (CH, Ar), 122.4 (CH, Ar),

77.2 (20). HRMS (ESI): m/z calcd. for C₂₉H₃₀NO₂P⁺[M⁺] 122.9 (CH, Ar), 123.7 (CH, Ar), 125.0 (CH, Ar), 125.5 (CH, Ar),

455.20087; found 455.20027.

126.1 (CH, Ar), 126.4 (CH, Ar), 127.0 (CH, Ar), 127.16 (CH, Ar),

127.23 (CH, Ar), 127.25 (C_q, Ar), 127.41 (CH, Ar), 127.44 (CH,

Ar), 128.08 (2ϫCH, Ar), 128.12 (2ϫCH, Ar), 128.34 (CH, Ar),

129.0 (2ϫCH, Ar), 129.2 (CH, Ar), 129.7 (C_q, Ar), 131.0 (C_q, Ar),

134.6 (C_q, Ar), 141.4 (d, J_C,P= 6.4 Hz, C_q, Ar), 142.2 (C_q, Ar),

147.7 (d, J_C,P= 9.2 Hz, C_q, Ar), 149.7 (d, J_C,P= 9.2 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 128.7 ppm. MS

(EI): m/z (%) = 234.2 (10), 196.2 (16), 149.1 (26), 145.1 (11), 144.1

(100), 116.1 (34), 115.1 (78), 106.2 (56), 105.2 (40), 91.2 (22), 89.2

(10), 79.2 (13). HRMS (ESI): m/z calcd. for C₃₅H₂₈NO₂P⁺[M⁺]

525.18522; found 525.18545.

(1R,3R)-3-(tert-Butoxy)-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-21d]: The com-

pound was synthesized from the borane adduct (0.6 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 256.9 mg

1

(0.56 mmol, 94%). H NMR (400 MHz, CDCl₃): δ = 1.25 (s, 9 H,

3

3 CH₃), 1.51 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 4.52 (dq, J_H,H= 7.0,

³J_H,P= 16.7 Hz, 1 H, CH), 5.77 (s, 1 H, CH), 7.07–7.33 (m, 10 H,

3

Ar), 7.34–7.41 (m, 1 H, Ar), 7.45–7.50 (m, 2 H, Ar), 7.67 (d, J_H,H

= 8.7 Hz, 1 H, Ar), 7.74 (d, ³J_H,H= 8.0 Hz, 1 H, Ar), 7.84 (d, ³J_H,H

= 8.4 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

19.2 (d, J = 8.7 Hz, CH₃), 30.8 (d, J = 8.6 Hz, 3ϫCH₃), 55.2 (d,

J = 28.2 Hz, CH), 55.9 (d, J = 5.7 Hz, 1 CH), 75.4 (d, J = 6.4 Hz,

OC_q), 121.4 (CH, Ar), 122.2 (CH, Ar), 122.8 (d, J = 8.7 Hz, C_q,

Ar), 123.7 (CH, Ar), 126.1 (CH, Ar), 126.8 (CH, Ar), 126.9 (CH,

Ar), 128.0 (4ϫCH, Ar), 128.2 (2ϫCH, Ar), 128.4 (2ϫCH, Ar),

128.7 (2ϫCH, Ar), 130.5 (2ϫC_q, Ar), 142.3 (d, J = 3.6 Hz, C_q,

Ar), 144.7 (d, J = 2.7 Hz, C_q, Ar), 145.0 (d, J = 3.5 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 114.1 ppm. MS

(EI): m/z (%) = 399.2 (36), 384.2 (13), 356.1 (10), 322.1 (21), 295.1

(10), 294.1 (49), 280.1 (17), 279.2 (20), 234.2 (17), 231.1 (16), 218.1

(91), 215.1 (14), 167.1 (34), 150.1 (10), 149.1 (100), 105.2 (49), 104.2

(12). HRMS (ESI): m/z calcd. for C₂₉H₃₀NO₂P⁺[M⁺] 455.20087;

found 455.20157.

(1R,3S)-3-(Naphthalen-2-yloxy)-1-phenyl-2-[(R)-1-phenylethyl]-2,3-

dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21g]: The

compound was synthesized from the borane adduct (0.6 mmol) by

following the general procedure GP-Syn4 for deprotection of li-

gands. The product was obtained as a colorless solid, yield

302.7 mg (0.58 mmol, 96%). [α]²_D⁵= +46.7 (c = 0.5, CH₂Cl₂). ¹H

3

NMR (400 MHz, CDCl₃): δ = 1.79 (d, J_H,H= 6.9 Hz, 3 H, CH₃),

3

4.96 (dq, J_H,H= 6.9, J_H,P= 12.1 Hz, 1 H, CH), 5.83 (d, J_H,P

=

3

4

5.7 Hz, 1 H, CH), 6.70 (dd, J_H,H= 8.8, J_H,H= 2.0 Hz, 1 H, Ar),

6.90–7.06 (m, 4 H, Ar), 7.12–7.42 (m, 13 H, Ar), 7.62 (m, 2 H, Ar),

3

7.71 (d, J_H,H= 8.2 Hz, 3 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 21.3 (d, J_C,P= 11.2 Hz, CH₃), 55.2 (d, J_C,P= 3.8 Hz,

CH), 59.3 (d, J_C,P= 38.4 Hz, CH), 114.8 (d, J_C,P= 12.6 Hz, CH,

Ar), 118.4 (d, J_C,P= 7.5 Hz, C_q, Ar), 120.5 (d, J_C,P= 3.6 Hz, CH,

Ar), 121.0 (d, J_C,P= 6.6 Hz, CH, Ar), 122.0 (CH, Ar), 123.7 (CH,

Ar), 124.2 (CH, Ar), 126.1 (CH, Ar), 126.4 (CH, Ar), 126.99 (CH,

Ar), 127.00 (CH, Ar), 127.21 (CH, Ar), 127.37 (CH, Ar), 127.41

(CH, Ar), 127.56 (CH, Ar), 127.93 (2ϫCH, Ar), 128.06 (2ϫCH,

Ar), 128.33 (CH, Ar), 128.93 (2 ϫ CH, Ar), 129.10 (CH, Ar),

129.14 (CH, Ar), 129.7 (C_q, Ar), 129.9 (C_q, Ar), 131.1 (C_q, Ar),

134.1 (C_q, Ar), 141.4 (d, J_C,P= 5.9 Hz, C_q, Ar), 142.2 (C_q, Ar),

147.8 (d, J_C,P= 9.0 Hz, C_q, Ar), 150.8 (d, J_C,P= 8.5 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 129.8 ppm. MS

(EI): m/z (%) = 382.4 (30), 278.3 (32), 115.3 (19), 105.3 (100).

HRMS (ESI): m/z calcd. for C₃₅H₂₉NO₂P⁺[M + H⁺] 526.19304;

found 526.19336.

(1R,3S)-3-Phenoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21e]: The compound

was synthesized from the borane adduct (0.5 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 209.2 mg

(0.44 mmol, 88%). [α]²_D⁴= +21.5 (c = 0.5, CH₂Cl₂). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.79 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 4.95

(dq, ³J_H,H= 6.9, ³J_H,P= 12.0 Hz, 1 H, CH), 5.80 (d, ³J_H,P= 5.9 Hz,

1 H, CH), 6.64 (m, 2 H, Ar), 6.91–7.04 (m, 4 H, Ar), 7.11–7.36 (m,

13 H, Ar), 7.68–7.73 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 21.3 (d, J = 11.0 Hz, CH₃), 55.0 (d, J = 3.8 Hz, CH),

59.1 (d, J = 38.1 Hz, CH), 118.5 (d, J = 7.4 Hz, C_q, Ar), 119.6

(2ϫCH, Ar), 120.5 (d, J = 3.5 Hz, CH, Ar), 122.0 (CH, Ar), 122.6

(CH, Ar), 123.7 (CH, Ar), 126.3 (CH, Ar), 126.9 (CH, Ar), 127.2

(CH, Ar), 127.32 (CH, Ar), 127.34 (CH, Ar), 127.8 (2ϫCH, Ar),

128.0 (2ϫCH, Ar), 128.3 (CH, Ar), 128.9 (2ϫCH, Ar), 129.1 (CH,

Ar), 129.2 (2ϫCH, Ar), 129.7 (C_q, Ar), 131.0 (C_q, Ar), 141.4 (d,

J = 5.9 Hz, C_q, Ar), 142.1 (C_q, Ar), 147.7 (d, J = 9.2 Hz, C_q, Ar),

153.1 (d, J = 8.9 Hz, OC_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz,

CDCl₃): δ = 129.9 ppm. MS (EI): m/z (%) = 382.2 (13), 279.2 (21),

278.1 (12), 167.1 (41), 150.1 (11), 149.1 (100), 105.2 (20), 71.3 (15).

HRMS (ESI): m/z calcd. for C₃₁H₂₆NO₂P⁺[M⁺] 475.16957; found

475.16988.

(1R,3S)-1-Phenyl-3-[(R)-1-phenylethoxy]-2-[(R)-1-phenylethyl]-2,3-

dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21h]: The

compound was synthesized from the borane adduct (0.4 mmol) by

following the general procedure GP-Syn4 for deprotection of li-

gands. The product was obtained as a semicrystalline colorless so-

lid, yield 173.2 mg (0.34 mmol, 86%). [α]²_D⁵= –25.4 (c = 0.63,

CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 1.21 (d, ³J_H,H= 6.5 Hz,

3

3 H, CH₃), 1.54 (d, J_H,H= 6.9 Hz, 3 H, CH₃), 4.70 (dq, J_H,H

=

3

6.9, J_H,P= 11.5 Hz, 1 H, CH), 4.92 (dq, J_H,H= 6.5, J_H,P

9.0 Hz, 1 H, CH), 5.63 (³J_H,P= 5.9 Hz, 1 H, CH), 6.79–6.87 (m, 5

H, Ar), 7.04–7.25 (m, 14 H, Ar), 7.63 (m, 2 H, Ar) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃): δ = 21.3 (d, J_C,P= 12.5 Hz, CH₃), 25.5

(d, J_C,P= 3.7 Hz, CH₃), 55.1 (d, J_C,P= 4.0 Hz, CH), 59.1 (d, J_C,P

(1R,3S)-3-(Naphthalen-1-yloxy)-1-phenyl-2-[(R)-1-phenylethyl]-2,3-

dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21f]: The

compound was synthesized from the borane adduct (0.6 mmol) by

following the general procedure GP-Syn4 for deprotection of li-

gands. The product was obtained as a colorless solid, yield

305.9 mg (0.58 mmol, 97%). [α]²_D³= –2.1 (c = 0.5, CH₂Cl₂). ¹H

= 38.6 Hz, CH), 73.6 (d, J_C,P= 23.9 Hz, OCH), 119.1 (d, J_C,P

=

7.3 Hz, C_q, Ar), 120.7 (d, J_C,P= 3.0 Hz, CH, Ar), 122.0 (CH, Ar),

123.4 (CH, Ar), 125.7 (2ϫCH, Ar), 126.2 (CH, Ar), 126.6 (CH,

Ar), 126.9 (CH, Ar), 127.0 (CH, Ar), 127.23 (CH, Ar), 127.25 (CH,

Ar), 127.7 (2ϫCH, Ar), 127.9 (2ϫCH, Ar), 128.0 (2ϫCH, Ar),

128.2 (CH, Ar), 128.8 (CH, Ar), 129.0 (2ϫCH, Ar), 129.4 (C_q,

Ar), 131.2 (C_q, Ar), 142.0 (d, J_C,P= 5.2 Hz, C_q, Ar), 142.5 (C_q,

3

NMR (400 MHz, CDCl₃): δ = 1.81 (d, J_H,H= 6.9 Hz, 3 H, CH₃),

3

5.00 (dq, J_H,H= 6.8, J_H,P= 12.4 Hz, 1 H, CH), 5.86 (d, J_H,P

=

Eur. J. Org. Chem. 2015, 6205–6230

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6223

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

Ar), 144.3 (d, J_C,P= 4.9 Hz, C_q, Ar), 148.3 (d, J_C,P= 8.6 Hz, C_q,

(2.0 mmol, 1.0 equiv.). Deviating from the general procedure, com-

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 136.2 ppm. MS mercially available dichloro(methoxy)phosphine (2.0 mmol,

(EI): m/z (%) = 503.1 (15), 426.1 (20), 400.1 (29), 399.1 (100), 398.0

(51), 357.0 (23), 356.0 (91), 322.0 (31), 295.0 (19), 294.0 (95), 231.1

(11), 218.0 (10), 215.1 (11), 105.1 (75), 79.2 (10). HRMS (ESI): m/z

calcd. for C₃₃H₃₁NO₂P⁺[M + H⁺] 504.20869; found 504.20880.

1.0 equiv.) was used. The product was obtained as a colorless solid,

yield 189.6 mg (0.44 mmol, 22%). H NMR (400 MHz, CDCl₃): δ

1

3

= 1.68 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 3.73 (d, J_H,P= 11.5 Hz, 3

3

H, OCH₃), 4.87 (dq, J_H,H= 7.0, J_H,P= 9.9 Hz, 1 H, CH), 5.76

(d, J_H,P= 10.6 Hz, 1 H, CH), 6.98 (m, 3 H, Ar), 7.13 (m, 5 H,

3

(1R,3S)-1-Phenyl-3-[(S)-1-phenylethoxy]-2-[(R)-1-phenylethyl]-2,3-

dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-21i]: The

compound was synthesized from the borane adduct (0.33 mmol)

by following the general procedure GP-Syn4 for deprotection of

ligands. The product was obtained as a semicrystalline colorless

solid, yield 128.0 mg (0.25 mmol, 77%). [α]²_D⁵= +29.9 (c = 0.1,

CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 0.94 (d, ³J_H,H= 6.5 Hz,

3

Ar), 7.28 (d, J_H,H= 8.8 Hz, 1 H, Ar), 7.37 (m, 3 H, Ar), 7.46 (m,

1 H, Ar), 7.77 (m, 3 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 18.9 (CH₃), 54.0 (d, J_C,P= 3.1 Hz, CH), 55.2 (d, J_C,P

= 1.4 Hz, OCH₃), 55.6 (d, J_C,P= 10.3 Hz, CH), 119.2 (d, J_C,P

=

3.4 Hz, CH, Ar), 121.6 (CH, Ar), 124.7 (d, J_C,P= 11.1 Hz, C_q, Ar),

125.1 (CH, Ar), 127.0 (CH, Ar), 127.1 (2ϫCH, Ar), 127.3 (CH,

Ar), 127.5 (CH, Ar), 127.8 (2ϫCH, Ar), 128.1 (2ϫCH, Ar), 128.2

(2ϫCH, Ar), 129.0 (CH, Ar), 129.4 (C_q, Ar), 130.0 (CH, Ar), 131.1

(C_q, Ar), 140.6 (d, J_C,P= 6.2 Hz, C_q, Ar), 141.0 (C_q, Ar), 144.3 (d,

J_C,P= 10.4 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ

= 111.7 ppm.

3

3 H, CH₃), 1.73 (d, J_H,H= 6.9 Hz, 3 H, CH₃), 4.73 (dq, J_H,H

=

3

6.5, J_H,P= 9.0 Hz, 1 H, CH), 4.80 (dq, J_H,H= 6.9, J_H,P

11.8 Hz, 1 H, CH), 5.68 (³J_H,P= 5.6 Hz, 1 H, CH), 6.82 (m, 1 H,

3

Ar), 6.89 (m, 2 H, Ar), 7.01–7.25 (m, 16 H, Ar), 7.55 (d, J_H,H

=

8.9 Hz, 1 H, Ar), 7.60 (m, 1 H, Ar) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃): δ = 21.2 (d, J_C,P= 11.4 Hz, CH₃), 24.8 (d, J_C,P

(1S,3S)-3-Methoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)-22a]: The compound

was synthesized from the borane adduct (0.5 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 167.4 mg

(0.41 mmol, 81%). ¹H NMR (300 MHz, CDCl₃): δ = 1.63 (d, ³J_H,H

= 5.0 Hz, CH₃), 54.5 (d, J_C,P= 3.5 Hz, CH), 58.8 (d, J_C,P

39.2 Hz, CH), 72.9 (d, J_C,P= 21.0 Hz, OCH), 118.5 (d, J_C,P

=

7.8 Hz, C_q, Ar), 120.7 (d, J_C,P= 3.4 Hz, CH, Ar), 121.9 (CH, Ar),

123.4 (CH, Ar), 125.9 (2ϫCH, Ar), 126.1 (CH, Ar), 126.7 (CH,

Ar), 126.9 (CH, Ar), 127.16 (CH, Ar), 127.26 (CH, Ar), 127.28

(CH, Ar), 127.84 (2 ϫ CH, Ar), 127.88 (2 ϫ CH, Ar), 128.1

(2ϫCH, Ar), 128.2 (CH, Ar), 128.7 (CH, Ar), 128.8 (2ϫCH, Ar),

129.4 (C_q, Ar), 131.2 (C_q, Ar), 141.8 (d, J_C,P= 4.7 Hz, C_q, Ar),

142.6 (C_q, Ar), 144.1 (d, J_C,P= 3.3 Hz, C_q, Ar), 148.4 (d, J_C,P

= 8.8 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

135.7 ppm. MS (EI): m/z (%) = 399.2 (12), 294.1 (11), 279.2 (22),

218.1 (26), 167.1 (44), 150.1 (12), 149.1 (100), 113.2 (11), 105.2

(21), 104.2 (12). HRMS (ESI): m/z calcd. for C₃₃H₃₀NO₂P⁺[M⁺]

503.20087; found 503.20127.

3

= 6.9 Hz, 3 H, CH₃), 3.42 (d, J_H,P= 12.0 Hz, 3 H, OCH₃), 4.21

3

(dq, J_H,H= 6.9, J_H,P= 12.9 Hz, 1 H, CH), 5.56 (s, 1 H, CH),

6.79 (m, 1 H, Ar), 7.05–7.53 (m, 12 H, Ar), 7.61–7.79 (m, 3 H,

Ar) ppm. ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 23.1 (d, J_C,P

19.0 Hz, CH₃), 48.2 (d, J_C,P= 17.3 Hz, OCH₃), 52.0 (d, J_C,P

=

5.6 Hz, CH), 58.4 (d, J_C,P= 26.6 Hz, CH), 119.8 (CH, Ar), 121.9

(C_q, Ar), 122.3 (CH, Ar), 123.7 (CH, Ar), 126.3 (CH, Ar), 126.5

(CH, Ar), 127.0 (CH, Ar), 127.2 (2ϫCH, Ar), 127.5 (2ϫCH, Ar),

128.5 (CH, Ar), 128.8 (CH, Ar), 128.9 (CH, Ar), 129.0 (2ϫCH,

Ar), 129.3 (CH, Ar), 130.2 (C_q, Ar), 131.3 (C_q, Ar), 141.7 (d, J_C,P

= 4.5 Hz, C_q, Ar), 143.7 (C_q, Ar), 146.9 (d, J_C,P= 7.4 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 116.7 ppm. MS

(EI): m/z (%) = 308.1 (13), 279.2 (31), 167.1 (62), 150.1 (12), 149.1

(100), 115.2 (30), 113.2 (11), 105.2 (11), 73.3 (14), 72.3 (12). HRMS

(ESI): m/z calcd. for C₂₆H₂₅NO₂P⁺[M + H⁺] 414.16174; found

414.16207.

Borane Adduct of (1S,3R)-3-Methoxy-1-phenyl-2-[(R)-1-phenyl-

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-

22a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn3 for ligand synthesis starting from 1-((S)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.). Deviating from the general procedure, com-

mercially available dichloro(methoxy)phosphine (2.0 mmol,

1.0 equiv.) was used. The product was obtained as a colorless solid,

(1S,3R)-3-Methoxy-1-phenyl-2-[(R)-1-phenylethyl]-2,3-dihydro-1H-

naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-22a]: The compound

was synthesized from the borane adduct (0.32 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 84.7 mg

(0.20 mmol, 64 %). ¹H NMR (300 MHz, CDCl₃): δ = 1.48 (dd,

1

yield 257.2 mg (0.60 mmol, 30%). H NMR (400 MHz, CDCl₃): δ

3

= 1.29 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 3.07 (d, J_H,P= 12.0 Hz, 3

3

H, OCH₃), 5.27 (dq, J_H,H= 7.0, J_H,P= 10.9 Hz, 1 H, CH), 5.94

3

(d, J_H,P= 13.7 Hz, 1 H, CH), 6.28 (d, J_H,H= 7.5 Hz, 2 H, Ar),

6.93 (t, J_H,H= 7.4 Hz, 2 H, Ar), 7.02 (t, ³J_H,H= 7.3 Hz, 1 H, Ar),

3

7.36 (d, J_H,H= 8.9 Hz, 1 H, Ar), 7.43 (m, 4 H, Ar), 7.54 (m, 4 H,

4

3

³J_H,H= 7.0, J_H,P= 1.1 Hz, 3 H, CH₃), 3.01 (d, J_H,P= 13.0 Hz, 3

Ar), 7.86 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ

= 17.1 (CH₃), 51.5 (d, J_C,P= 3.9 Hz, CH), 52.1 (d, J_C,P= 2.0 Hz,

OCH₃), 56.7 (d, J_C,P= 15.3 Hz, CH), 119.1 (d, J_C,P= 9.7 Hz, C_q,

Ar), 119.8 (d, J_C,P= 7.0 Hz, CH, Ar), 121.9 (CH, Ar), 124.8 (CH,

Ar), 127.3 (CH, Ar), 127.5 (CH, Ar), 127.8 (2ϫCH, Ar), 128.0

(2ϫCH, Ar), 128.3 (CH, Ar), 128.6 (2ϫCH, Ar), 128.9 (CH, Ar),

129.0 (2ϫCH, Ar), 130.1 (CH, Ar), 130.2 (C_q, Ar), 130.5 (C_q, Ar),

139.8 (C_q, Ar), 141.2 (d, J_C,P= 9.1 Hz, C_q, Ar), 148.1 (d, J_C,P

= 8.9 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

118.5 ppm.

3

H, OCH₃), 4.92 (dq, J_H,H= 7.0, J_H,P= 7.5 Hz, 1 H, CH), 5.60

(d, ³J_H,P= 5.4 Hz, 1 H, CH), 6.76 (m, 2 H, Ar), 7.06 (m, 3 H, Ar),

3

7.22–7.50 (m, 9 H, Ar), 7.76 (d, J_H,H= 8.6 Hz, 2 H, Ar) ppm.

¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 21.3 (d, J_C,P= 16.5 Hz,

CH₃), 49.2 (d, J_C,P= 15.5 Hz, OCH₃), 53.0 (d, J_C,P= 3.5 Hz, CH),

58.4 (d, J_C,P= 35.9 Hz, CH), 120.9 (d, J_C,P= 3.1 Hz, CH, Ar),

122.4 (CH, Ar), 123.7 (CH, Ar), 123.8 (C_q, Ar), 126.5 (CH, Ar),

126.7 (CH, Ar), 127.6 (3ϫCH, Ar), 127.7 (2ϫCH, Ar), 128.5 (CH,

Ar), 128.6 (2ϫCH, Ar), 128.8 (2ϫCH, Ar), 129.2 (CH, Ar), 129.9

(C_q, Ar), 132.3 (C_q, Ar), 141.8 (d, J_C,P= 4.5 Hz, C_q, Ar), 142.3

Borane Adduct of (1S,3S)-3-Methoxy-1-phenyl-2-[(R)-1-phenyl- (C_q, Ar), 145.9 (d, J_C,P= 13.6 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR

ethyl]-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(S_P)- (121 MHz, CDCl₃): δ = 132.6 ppm. MS (EI): m/z (%) = 279.2 (22),

22a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn3 for ligand synthesis starting from 1-((S)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

167.1 (43), 150.1 (12), 149.1 (100), 73.3 (11), 71.3 (12). HRMS

(ESI): m/z calcd. for C₂₆H₂₅NO₂P⁺[M + H⁺] 414.16174; found

414.16196.

6224

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Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

Borane Adduct of (R)-1-Phenyl-N-{(R)-phenyl[2-({(1R,3S)-1-phenyl- (d, J_H,H= 7.1 Hz, 3 H, CH₃), 2.95 (m, 2 H, CH₂), 3.40 (m, 2 H,

3

2-[(R)-1-phenylethyl]-1,2-dihydro-3H-naphtho[1,2-e][1,3,2]oxaza-

phosphinin-3-yl}oxy)naphthalen-1-yl]methyl}ethan-1-amine

(23·BH₃): The compound was isolated by column chromatography

as a side-product in the syntheses following the general procedure

GP-Syn2 and GP-Syn3 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol. The

product was obtained as a colorless solid. ¹H NMR (400 MHz,

CH₂), 5.07 (dq, J_H,H= 7.0, J_H,P= 11.2 Hz, 1 H, CH), 5.62 (d,

³J_H,P= 16.9 Hz, 1 H, CH), 7.04 (d, J_H,H= 8.5 Hz, 1 H, Ar), 7.15

3

(m, 2 H, Ar), 7.23 (m, 6 H, Ar), 7.32 (m, 3 H, Ar), 7.54 (d, J_H,H

= 7.4 Hz, 2 H, Ar), 7.71 (t, ³J_H,H= 9.4 Hz, 2 H, Ar) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃): δ = 14.4 (2ϫCH₃), 18.5 (CH₃), 39.0 (d,

J_C,P= 6.3 Hz, 2ϫCH₂), 54.2 (d, J_C,P= 14.3 Hz, CH), 56.7 (CH),

120.0 (d, J_C,P= 4.8 Hz, CH, Ar), 121.4 (CH, Ar), 123.9 (d, J_C,P

6.7 Hz, C_q, Ar), 124.5 (CH, Ar), 126.6 (CH, Ar), 127.5 (CH, Ar),

=

3

CDCl₃): δ = 1.21 (br. s, 3 H, CH₃), 1.63 (d, J_H,H= 6.5 Hz, 3 H,

3

CH₃), 3.72 (q, J_H,H= 6.3 Hz, 1 H, CH), 5.26 (m, 1 H, CH), 5.65 127.6 (CH, Ar), 128.4 (4ϫCH, Ar), 128.5 (2ϫCH, Ar), 128.6 (CH,

(br. d, ³J_H,P= 8.7 Hz, 1 H, CH), 5.74 (d, ³J_H,P= 16.7 Hz, 1 H, CH), Ar), 128.7 (2ϫCH, Ar), 129.3 (C_q, Ar), 129.7 (CH, Ar), 130.6 (C_q,

6.76–7.80 (m, 32 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ Ar), 139.6 (d, J_C,P= 4.8 Hz, C_q, Ar), 142.9 (C_q, Ar), 148.1 (d, J_C,P

= 20.0 (CH₃), 25.7 (CH₃), 54.8 (d, J = 3.5 Hz, CH), 55.4 (d, J = = 6.1 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

15.8 Hz, CH), 55.5 (CH), 56.1 (CH), 119.3 (d, J = 6.5 Hz, CH,

Ar), 120.4 (CH, Ar), 121.6 (CH, Ar), 122.0 (C_q, Ar), 124.7 (CH,

Ar), 124.8 (CH, Ar), 125.9 (CH, Ar), 126.3 (CH, Ar), 126.6 (CH,

Ar), 126.8 (CH, Ar), 127.1 (5ϫCH, Ar), 127.4 (4ϫCH, Ar), 127.8

(4 ϫ CH, Ar), 128.0 (2 ϫ CH, Ar), 128.2 (2 ϫ CH, Ar), 128.4

(3ϫCH, Ar), 128.68 (C_q, Ar), 128.73 (CH, Ar), 128.78 (CH, Ar),

129.7 (C_q, Ar), 129.8 (CH, Ar), 130.3 (C_q, Ar), 131.5 (C_q, Ar),

132.8 (C_q, Ar), 138.9 (d, J = 4.7 Hz, C_q, Ar), 140.4 (C_q, Ar), 143.8

(C_q, Ar), 146.2 (C_q, Ar), 146.8 (d, J = 8.6 Hz, C_q, Ar), 147.7 (d, J

= 2.1 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

116.3 ppm.

111.5 ppm.

Borane Adduct of (1R,3S)-N,N-Diethyl-1-phenyl-2-[(R)-1-phenyleth-

yl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(S_P)-

24a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn3 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(4.0 mmol, 1.0 equiv.). Deviating from the general procedure, com-

mercially available 1,1-dichloro-N,N-diethylphosphinamine

(4.0 mmol, 1.0 equiv.) was used. The product was obtained as a

colorless solid, yield 562.1 mg (1.20 mmol, 30 %). ¹H NMR

3

(400 MHz, CDCl₃): δ = 0.92 (t, J_H,H= 7.0 Hz, 6 H, CH₃), 1.38

3

(R)-1-Phenyl-N-{(R)-phenyl[2-({(1R,3S)-1-phenyl-2-[(R)-1-phenyl-

ethyl]-1,2-dihydro-3H-naphtho[1,2-e][1,3,2]oxazaphosphinin-3-

yl}oxy)naphthalen-1-yl]methyl}ethan-1-amine (23): The compound

was synthesized from the borane adduct (0.6 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 427.7 mg

(0.58 mmol, 97%). ¹H NMR (400 MHz, CDCl₃): δ = 1.15 (d, ³J_H,H

(d, J_H,H= 7.2 Hz, 3 H, CH₃), 3.02 (m, 4 H, CH₂), 4.85 (dq, J_H,H

3

= 7.1 Hz, J_H,P= 10.7 Hz, 1 H, CH), 5.82 (d, J_H,P= 12.4 Hz, 1

H, CH), 7.16 (m, 1 H, Ar), 7.25 (m, 3 H, Ar), 7.34 (m, 2 H, Ar),

7.39 (m, 5 H, Ar), 7.69 (m, 5 H, Ar) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃): δ = 13.4 (2ϫCH₃), 19.7 (CH₃), 38.5 (d, J_C,P

=

4.4 Hz, 2ϫCH₂), 54.9 (CH), 56.1 (d, J_C,P= 13.6 Hz, CH), 119.7

(d, J_C,P= 3.5 Hz, CH, Ar), 121.6 (CH, Ar), 123.7 (d, J_C,P= 9.2 Hz,

C_q, Ar), 124.6 (CH, Ar), 127.0 (CH, Ar), 127.6 (CH, Ar), 127.9

(3 ϫ CH, Ar), 128.4 (2 ϫ CH, Ar), 128.56 (2 ϫ CH, Ar), 128.59

(2ϫCH, Ar), 128.9 (CH, Ar), 129.2 (C_q, Ar), 129.6 (CH, Ar), 130.7

(C_q, Ar), 140.1 (d, J_C,P= 4.5 Hz, C_q, Ar), 143.9 (C_q, Ar), 145.8 (d,

J_C,P= 11.5 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ

= 100.7 ppm.

3

= 6.4 Hz, 3 H, CH₃), 1.72 (d, J_H,H= 6.9 Hz, 3 H, CH₃), 3.52 (m,

3

1 H, CH), 4.64 (m, 1 H, CH), 5.54 (m, 1 H, CH), 5.71 (d, J_H,P

=

6.0 Hz, 1 H, CH), 6.83–7.38 (m, 28 H, Ar), 7.65–7.82 (m, 4 H,

Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 20.9 (d, J =

9.0 Hz, CH₃), 25.7 (CH₃), 54.1 (d, J = 4.5 Hz, CH), 55.4 (CH),

55.8 (CH), 58.0 (d, J = 42.5 Hz, CH), 120.4 (d, J = 3.3 Hz, CH,

Ar), 121.7 (d, J = 9.5 Hz, C_q, Ar), 121.9 (CH, Ar), 123.7 (CH, Ar),

124.1 (CH, Ar), 125.9 (CH, Ar), 126.0 (d, J = 4.4 Hz, C_q, Ar),

126.1 (CH, Ar), 126.2 (CH, Ar), 126.7 (CH, Ar), 126.8 (CH, Ar),

127.05 (2ϫCH, Ar), 127.06 (3ϫCH, Ar), 127.10 (CH, Ar), 127.2

(2 ϫ CH, Ar), 127.7 (2 ϫ CH, Ar), 127.9 (2 ϫ CH, Ar), 128.06

(2 ϫ CH, Ar), 128.17 (2 ϫ CH, Ar), 128.23 (CH, Ar), 128.50

(3ϫCH, Ar), 128.54 (2ϫCH, Ar), 128.8 (d, J = 3.7 Hz, C_q, Ar),

128.7 (C_q, Ar), 129.0 (CH, Ar), 129.6 (C_q, Ar), 130.8 (C_q, Ar),

141.1 (d, J = 4.8 Hz, C_q, Ar), 141.9 (C_q, Ar), 144.6 (C_q, Ar), 146.3

(C_q, Ar), 147.9 (d, J = 8.7 Hz, C_q, Ar), 149.4 (d, J = 8.0 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 133.7 ppm. MS

(EI): m/z (%) = 382.2 (31), 363.3 (18), 287.2 (12), 286.2 (65), 285.2

(14), 279.2 (18), 278.1 (32), 234.2 (17), 231.2 (48), 218.1 (13), 215.2

(12), 202.2 (15), 182.2 (49), 181.2 (13), 167.1 (26), 149.1 (68), 106.2

(52), 105.2 (100), 91.2 (10), 79.2 (17), 77.2 (16). HRMS (ESI): m/z

calcd. for C₅₀H₄₃N₂O₂P⁺[M⁺] 734.30567; found 734.30641.

Borane Adduct of (1R,3R)-1-Phenyl-2-[(R)-1-phenylethyl]-3-(piper-

idin-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine

[(R_P)-24b·BH₃]: The compound was synthesized by following the

general procedure GP-Syn1 for ligand synthesis starting from 1-

((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and piperidine (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 809.0 mg

(1.68 mmol, 84%). ¹H NMR (400 MHz, CDCl₃): δ = 1.49 (m, 3 H,

3

CH₃, 6 H, CH₂), 3.06 (m, 4 H, CH₂), 5.04 (dq, J_H,H= 7.0 Hz,

³J_H,P= 11.6 Hz, 1 H, CH), 5.62 (d, J_H,P= 16.2 Hz, 1 H, CH),

3

7.04–7.22 (m, 9 H, Ar), 7.29 (m, 3 H, Ar), 7.45 (m, 2 H, Ar), 7.66

(m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.0

(CH₃), 24.5 (CH₂), 26.4 (d, J_C,P= 2.8 Hz, 2ϫCH₂), 45.4 (d, J_C,P

= 3.9 Hz, 2ϫCH₂), 54.6 (d, J_C,P= 13.4 Hz, CH), 56.6 (CH), 119.9

(d, J_C,P= 4.9 Hz, CH, Ar), 121.4 (CH, Ar), 123.4 (d, J_C,P= 7.3 Hz,

C_q, Ar), 124.4 (CH, Ar), 126.6 (CH, Ar), 127.3 (CH, Ar), 127.5

(CH, Ar), 128.29 (4ϫCH, Ar), 128.39 (2ϫCH, Ar), 128.48 (CH,

Ar), 128.54 (2ϫCH, Ar), 129.4 (C_q, Ar), 129.6 (CH, Ar), 130.4

(C_q, Ar), 139.6 (d, J_C,P= 4.1 Hz, C_q, Ar), 142.7 (C_q, Ar), 148.1 (d,

J_C,P= 6.4 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ

= 108.6 ppm.

Borane Adduct of (1R,3R)-N,N-Diethyl-1-phenyl-2-[(R)-1-phenyl-

ethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-

24a·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(4.0 mmol, 1.0 equiv.). Deviating from the general procedure, com-

mercially available 1,1-dichloro-N,N-diethylphosphinamine

(4.0 mmol, 1.0 equiv.) was used. The product was obtained as a

Borane Adduct of (1R,3S)-1-Phenyl-2-[(R)-1-phenylethyl]-3-(piper-

idin-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine

[(S_P)-24b·BH₃]: The compound was synthesized by following the

colorless solid, yield 1.757 g (3.75 mmol, 94 %). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.14 (t, J_H,H= 7.0 Hz, 6 H, CH₃), 1.44 general procedure GP-Syn3 for ligand synthesis starting from 1-

Eur. J. Org. Chem. 2015, 6205–6230

www.eurjoc.org

6225

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and piperidine (2.0 mmol, 1.0 equiv.). The

product was obtained as a colorless solid, yield 227.7 mg

127.2 (CH, Ar), 127.48 (2ϫCH, Ar), 127.52 (2ϫCH, Ar), 127.57

(CH, Ar), 128.0 (CH, Ar), 128.2 (2ϫCH, Ar), 128.4 (2ϫCH, Ar),

128.57 (2ϫCH, Ar), 128.61 (2ϫCH, Ar), 128.8 (CH, Ar), 129.0

(0.47 mmol, 24%). ¹H NMR (400 MHz, CDCl₃): δ = 1.28 (m, 4 H, (C_q, Ar), 129.9 (CH, Ar), 130.6 (C_q, Ar), 139.8 (d, J_C,P= 3.9 Hz,

CH₂), 1.37 (d, ³J_H,H= 7.2 Hz, 3 H, CH₃), 1.47 (m, 2 H, CH₂), 2.86 C_q, Ar), 140.7 (d, J_C,P= 1.7 Hz, C_q, Ar), 144.1 (C_q, Ar), 146.1 (d,

(m, 2 H, CH₂), 3.06 (m, 2 H, CH₂), 4.85 (dq, ³J_H,H= 7.2 Hz, ³J_H,PJ_C,P= 10.8 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ

3

= 10.4 Hz, 1 H, CH), 5.83 (d, J_H,P= 12.5 Hz, 1 H, CH), 7.07– = 101.4 ppm.

7.42 (m, 11 H, Ar), 7.66 (m, 5 H, Ar) ppm. ¹³C{¹H} NMR

Borane Adduct of (1R,3R)-N-Methyl-1-phenyl-2-[(R)-1-phenylethyl]-

(100 MHz, CDCl₃): δ = 19.6 (d, J_C,P= 1.0 Hz, CH₃), 24.2 (CH₂),

N-[(S)-1-phenylethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-

26.2 (d, J_C,P= 3.1 Hz, 2ϫCH₂), 46.1 (d, J_C,P= 1.9 Hz, 2ϫCH₂),

3(2H)-amine [(R_P)-24d·BH₃]: The compound was synthesized by

following the general procedure GP-Syn1 for ligand synthesis

54.9 (CH), 56.2 (d, J_C,P= 13.0 Hz, CH), 119.5 (d, J_C,P= 3.5 Hz,

CH, Ar), 121.4 (CH, Ar), 123.8 (d, J_C,P= 9.1 Hz, C_q, Ar), 124.6

starting from 1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)-

(CH, Ar), 127.0 (CH, Ar), 127.5 (CH, Ar), 127.7 (3ϫCH, Ar),

naphthalen-2-ol (2.0 mmol, 1.0 equiv.) and (S)-N-methyl-1-phen-

128.2 (2ϫCH, Ar), 128.4 (2ϫCH, Ar), 128.5 (2ϫCH, Ar), 128.8

ylethanamine (2.0 mmol, 1.0 equiv.). The product was obtained as

(CH, Ar), 129.1 (C_q, Ar), 129.6 (CH, Ar), 130.6 (C_q, Ar), 140.1 (d,

a colorless solid, yield 785.1 mg (1.48 mmol, 74 %). ¹H NMR

J_C,P= 4.3 Hz, C_q, Ar), 143.8 (C_q, Ar), 145.9 (d, J_C,P= 11.1 Hz,

3

(400 MHz, CDCl₃): δ = 1.47 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.53

C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 98.7 ppm.

(d, ³J_H,H= 6.9 Hz, 3 H, CH₃), 2.27 (d, ³J_H,P= 7.9 Hz, 3 H, NCH₃),

3

Borane Adduct of (1R,3R)-N-Methyl-1-phenyl-N,2-bis[(R)-1-phenyl-

ethyl]-1H-naphtho[1,2-e][1,3,2]oxaza-phosphinine-3(2H)-amine

[(R_P)-24c·BH₃]: The compound was synthesized by following the

general procedure GP-Syn1 for ligand synthesis starting from 1-

((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and (R)-N-methyl-1-phenylethanamine

(2.0 mmol, 1.0 equiv.). The product was obtained as a colorless so-

lid, yield 841.3 mg (1.59 mmol, 79 %). ¹H NMR (400 MHz,

5.17 (dq, J_H,H= 7.1 Hz, J_H,P= 11.1 Hz, 1 H, CH), 5.47 (dq,

³J_H,H= 6.7 Hz, ³J_H,P= 13.1 Hz, 1 H, CH), 5.65 (d, ³J_H,P= 16.8 Hz,

1 H, CH), 7.01–7.10 (m, 2 H, Ar), 7.14 (m, 3 H, Ar), 7.18–7.31 (m,

7 H, Ar), 7.39 (m, 3 H, Ar), 7.52 (d, ³J_H,H= 7.6 Hz, 2 H, Ar), 7.58

3

(d, J_H,H= 7.3 Hz, 2 H, Ar), 7.69 (d, J_H,H= 8.0 Hz, 1 H, Ar),

7.73 (d, J_H,H= 8.9 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

3

CDCl₃): δ = 17.0 (d, J_C,P= 4.6 Hz, CH₃), 18.7 (CH₃), 26.4 (d, J_C,P

= 3.7 Hz, NCH₃), 53.5 (d, J_C,P= 16.6 Hz, CH), 54.2 (d, J_C,P

=

3

CDCl₃): δ = 1.21 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.67 (d, J_H,H

=

14.4 Hz, CH), 56.8 (CH), 120.0 (d, J_C,P= 4.7 Hz, CH, Ar), 121.4

(CH, Ar), 123.9 (d, J_C,P= 6.7 Hz, C_q, Ar), 124.5 (CH, Ar), 126.7

(CH, Ar), 127.1 (CH, Ar), 127.4 (2ϫCH, Ar), 127.5 (CH, Ar),

127.6 (CH, Ar), 128.3 (2ϫCH, Ar), 128.45 (2ϫCH, Ar), 128.48

(2ϫCH, Ar), 128.6 (3ϫCH, Ar), 128.9 (2ϫCH, Ar), 129.2 (C_q,

Ar), 129.7 (CH, Ar), 130.7 (C_q, Ar), 139.5 (d, J_C,P= 4.8 Hz, C_q,

Ar), 140.9 (d, J_C,P= 3.6 Hz, C_q, Ar), 142.7 (C_q, Ar), 148.0 (d, J_C,P

= 6.0 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

111.4 ppm.

3

6.9 Hz, 3 H, CH₃), 2.30 (d, J_H,P= 8.1 Hz, 3 H, NCH₃), 5.21 (dq,

³J_H,H= 7.1 Hz, J_H,P= 10.7 Hz, 1 H, CH), 5.41 (dq, J_H,H

=

3

6.9 Hz, J_H,P= 11.6 Hz, 1 H, CH), 5.62 (d, J_H,P= 17.3 Hz, 1 H,

CH), 7.00 (d, ³J_H,H= 8.5 Hz, 1 H, Ar), 7.07 (m, 1 H, Ar), 7.14 (m,

3 H, Ar), 7.20–7.33 (m, 9 H, Ar), 7.40 (m, 3 H, Ar), 7.58 (m, 2 H,

Ar), 7.71 (d, J_H,H= 8.1 Hz, 1 H, Ar), 7.76 (d, J_H,H= 8.9 Hz, 1

H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 16.7 (CH₃),

18.3 (CH₃), 25.9 (d, J_C,P= 3.7 Hz, NCH₃), 54.1 (d, J_C,P= 16.2 Hz,

3

CH), 54.3 (d, J_C,P= 14.1 Hz, CH), 56.6 (CH), 120.0 (d, J_C,P

=

Borane Adduct of (1R,3S)-N-Methyl-1-phenyl-2-[(R)-1-phenylethyl]-

N-[(S)-1-phenylethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-

3(2H)-amine [(S_P)-24d·BH₃]: The compound was synthesized by

following the general procedure GP-Syn3 for ligand synthesis

starting from 1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)-

naphthalen-2-ol (2.0 mmol, 1.0 equiv.) and (S)-N-methyl-1-pheny-

lethanamine (2.0 mmol, 1.0 equiv.). The product was obtained as a

colorless solid, yield 211.1 mg (0.40 mmol, 20 %). ¹H NMR

4.7 Hz, CH, Ar), 121.4 (CH, Ar), 123.9 (d, J_C,P= 6.7 Hz, C_q, Ar),

124.5 (CH, Ar), 126.7 (CH, Ar), 127.3 (CH, Ar), 127.5 (CH, Ar),

127.6 (CH, Ar), 127.7 (2 ϫ CH, Ar), 128.2 (2ϫ CH, Ar), 128.4

(2ϫCH, Ar), 128.5 (2ϫCH, Ar), 128.6 (CH, Ar), 128.7 (2ϫCH,

Ar), 129.0 (2ϫCH, Ar), 129.2 (C_q, Ar), 129.8 (CH, Ar), 130.7 (C_q,

Ar), 139.6 (d, J_C,P= 5.0 Hz, C_q, Ar), 140.9 (d, J_C,P= 8.4 Hz, C_q,

Ar), 142.5 (C_q, Ar), 148.1 (d, J_C,P= 6.3 Hz, C_q, Ar) ppm. ³¹P{¹H}

NMR (162 MHz, CDCl₃): δ = 111.2 ppm.

3

(400 MHz, CDCl₃): δ = 1.39 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.61

Borane Adduct of (1R,3S)-N-Methyl-1-phenyl-N,2-bis[(R)-1-phenyl-

ethyl]-1H-naphtho[1,2-e][1,3,2]oxaza-phosphinine-3(2H)-amine

[(S_P)-24c·BH₃]: The compound was synthesized by following the

general procedure GP-Syn3 for ligand synthesis starting from 1-

((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and (R)-N-methyl-1-phenylethanamine

(2.0 mmol, 1.0 equiv.). The product was obtained as a colorless so-

lid, yield 204.4 mg (0.39 mmol, 19 %). ¹H NMR (400 MHz,

(d, ³J_H,H= 6.9 Hz, 3 H, CH₃), 1.66 (d, ³J_H,P= 8.0 Hz, 3 H, NCH₃),

3

4.98 (dq, J_H,H= 7.2 Hz, J_H,P= 10.9 Hz, 1 H, CH), 5.48 (dq,

³J_H,H= 6.9 Hz, ³J_H,P= 10.6 Hz, 1 H, CH), 5.86 (d, ³J_H,P= 11.3 Hz,

1 H, CH), 7.13–7.48 (m, 16 H, Ar), 7.66 (d, J_H,H= 8.9 Hz, 1 H,

Ar), 7.71 (d, J_H,H= 8.6 Hz, 2 H, Ar), 7.79 (d, J_H,H= 7.8 Hz, 2

H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 16.1 (CH₃),

19.6 (d, J_C,P= 2.1 Hz, CH₃), 27.0 (d, J_C,P= 5.5 Hz, NCH₃), 54.0

(d, J_C,P= 13.7 Hz, CH), 54.5 (CH), 56.5 (d, J_C,P= 12.9 Hz, CH),

3

CDCl₃): δ = 1.41 (d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.55 (d, J_H,H

=

119.2 (d, J_C,P= 3.4 Hz, CH, Ar), 121.6 (CH, Ar), 124.1 (d, J_C,P

=

3

6.9 Hz, 3 H, CH₃), 1.66 (d, J_H,P= 7.8 Hz, 3 H, NCH₃), 4.94 (dq,

9.5 Hz, C_q, Ar), 124.7 (CH, Ar), 127.0 (CH, Ar), 127.4 (CH, Ar),

127.5 (2ϫCH, Ar), 127.6 (CH, Ar), 127.8 (2ϫCH, Ar), 127.9 (CH,

Ar), 128.3 (2ϫCH, Ar), 128.4 (2ϫCH, Ar), 128.6 (2ϫCH, Ar),

128.7 (2ϫCH, Ar), 129.0 (CH, Ar), 129.2 (C_q, Ar), 130.0 (CH,

Ar), 130.8 (C_q, Ar), 139.5 (d, J_C,P= 3.8 Hz, C_q, Ar), 140.7 (d, J_C,P

= 10.0 Hz, C_q, Ar), 144.3 (C_q, Ar), 146.2 (d, J_C,P= 10.5 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 101.4 ppm.

³J_H,H= 7.1 Hz, J_H,P= 10.7 Hz, 1 H, CH), 5.51 (dq, J_H,H

=

3

6.7 Hz, J_H,P= 13.0 Hz, 1 H, CH), 5.89 (d, J_H,P= 11.9 Hz, 1 H,

CH), 6.98 (d, J_H,H= 8.8 Hz, 1 H, Ar), 7.14 (m, 1 H, Ar), 7.22–

7.43 (m, 12 H, Ar), 7.50 (m, 3 H, Ar), 7.60 (d, J_H,H= 8.1 Hz, 1

H, Ar), 7.68 (d, J_H,H= 8.6 Hz, 1 H, Ar), 7.77 (d, J_H,H= 7.6 Hz,

2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 16.2 (d, J_C,P

= 6.8 Hz, CH₃), 19.6 (d, J_C,P= 1.8 Hz, CH₃), 27.4 (d, J_C,P= 5.3 Hz,

3

NCH₃), 53.8 (d, J_C,P= 13.6 Hz, CH), 54.6 (CH), 56.4 (d, J_C,P

13.4 Hz, CH), 119.0 (d, J_C,P= 3.4 Hz, CH, Ar), 121.4 (CH, Ar),

124.2 (d, J_C,P= 9.2 Hz, C_q, Ar), 124.6 (CH, Ar), 127.0 (CH, Ar),

=

Borane Adduct of (1R,3R)-1-Phenyl-N,N,2-tris[(R)-1-phenylethyl]-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-

24e·BH₃]: The compound was synthesized by following the general

6226

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Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

124.4 (CH, Ar), 125.4 (2ϫCH, Ar), 126.5 (CH, Ar), 126.9 (CH,

Ar), 127.2 (CH, Ar), 127.73 (2ϫ, CH, Ar), 127.78 (2ϫCH, Ar),

(2.0 mmol, 1.0 equiv.) and (R)-bis[(R)-1-phenylethyl]amine 127.87 (2ϫCH, Ar), 127.90 (2ϫCH, Ar), 127.98 (2ϫCH, Ar),

(2.0 mmol, 1.0 equiv.). The product was obtained as a colorless so- 128.01 (2ϫCH, Ar), 128.2 (CH, Ar), 128.6 (4ϫCH, Ar), 129.6

lid, yield 907.3 mg (1.46 mmol, 73 %). ¹H NMR (400 MHz, (CH, Ar), 129.9 (C_q, Ar), 130.0 (C_q, Ar), 139.2 (d, J_C,P= 2.9 Hz,

3

CDCl₃): δ = 0.88 (d, J_H,H= 7.2 Hz, 6 H, CH₃), 1.96 (d, J_H,H

=

C_q, Ar), 139.8 (C_q, Ar), 144.0 (d, J_C,P= 5.8 Hz, 2ϫC_q, Ar), 147.7

7.1 Hz, 3 H, CH₃), 5.01 (dq, J_H,H= 7.1 Hz, J_H,P= 12.6 Hz, 2 H, (d, J_C,P= 7.5 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃):

3

CH), 5.55 (dq, ³J_H,H= 7.0 Hz, J_H,P= 11.6 Hz, 1 H, CH), 5.86 (d,

δ = 108.5 ppm.

3

³J_H,P= 18.4 Hz, 1 H, CH), 6.80 (d, J_H,H= 8.4 Hz, 1 H, Ar), 6.99

3

(1R,3R)-N,N-Diethyl-1-phenyl-2-[(R)-1-phenylethyl]-1H-naphtho-

[1,2-e][1,3,2]oxaza-phosphinine-3(2H)-amine [(R_P)-24a]: The com-

pound was synthesized from the borane adduct (0.7 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 283.2 mg

(0.62 mmol, 89%). ¹H NMR (400 MHz, CDCl₃): δ = 0.96 (t, ³J_H,H

(m, 3 H, Ar), 7.10 (m, 4 H, Ar), 7.22–7.36 (m, 13 H, Ar), 7.55 (m,

3 H, Ar), 7.78 (d, ³J_H,H= 8.1 Hz, 1 H, Ar), 7.87 (d, ³J_H,H= 8.8 Hz,

1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 19.4

(2ϫCH₃), 21.7 (CH₃), 53.1 (d, J_C,P= 7.9 Hz, 2ϫCH), 55.5 (d,

J_C,P= 17.7 Hz, CH), 57.2 (d, J_C,P= 2.1 Hz, CH), 120.1 (d, J_C,P

=

5.2 Hz, CH, Ar), 121.4 (CH, Ar), 124.60 (d, J_C,P= 6.3 Hz, C_q, Ar),

124.62 (CH, Ar), 126.5 (CH, Ar), 127.2 (2ϫCH, Ar), 127.58 (CH,

Ar), 127.61 (CH, Ar), 127.8 (4 ϫ CH, Ar), 128.4 (7 ϫ CH, Ar),

128.67 (2ϫ, CH, Ar), 128.69 (4ϫCH, Ar), 129.3 (C_q, Ar), 129.7

(CH, Ar), 130.6 (C_q, Ar), 139.5 (d, J_C,P= 4.4 Hz, C_q, Ar), 141.7

3

= 7.0 Hz, 6 H, CH₃), 1.61 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 2.68 (m,

3

2 H, CH₂), 2.99 (m, 2 H, CH₂), 4.88 (dq, J_H,H= 7.0 Hz, J_H,P

=

3

11.2 Hz, 1 H, CH), 5.67 (d, J_H,P= 7.9 Hz, 1 H, CH), 6.93 (m, 1

H, Ar), 7.01 (m, 2 H, Ar), 7.08–7.33 (m, 11 H, Ar), 7.66 (m, 2 H,

Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 15.0 (d, J_C,P

3.0 Hz, 2 ϫ CH₃), 19.9 (d, J_C,P= 5.0 Hz, CH₃), 38.3 (d, J_C,P

21.8 Hz, 2ϫCH₂), 56.3 (d, J_C,P= 2.6 Hz, CH), 56.6 (d, J_C,P

=

(C_q, Ar), 142.1 (d, J_C,P= 4.9 Hz, 2ϫC_q, Ar), 149.3 (d, J_C,P

=

6.6 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

117.6 ppm.

38.0 Hz, CH), 121.2 (d, J_C,P= 3.1 Hz, CH, Ar), 123.5 (CH, Ar),

124.7 (d, J_C,P= 6.0 Hz, C_q, Ar), 126.1 (CH, Ar), 126.58 (CH, Ar),

126.61 (CH, Ar), 127.47 (CH, Ar), 127.53 (CH, Ar), 127.9 (2ϫCH,

Ar), 128.1 (2ϫCH, Ar), 128.2 (CH, Ar), 128.4 (2ϫCH, Ar), 128.5

(CH, Ar), 128.7 (CH, Ar), 129.4 (C_q, Ar), 130.4 (C_q, Ar), 142.1 (d,

J_C,P= 3.7 Hz, C_q, Ar), 144.5 (C_q, Ar), 150.3 (d, J_C,P= 3.5 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 135.4 ppm. MS

(EI): m/z (%) = 279.2 (19), 232.1 (16), 231.1 (38), 167.1 (36), 150.1

(10), 149.1 (100), 144.1 (10), 106.2 (50), 105.2 (39), 104.1 (10), 91.2

(10), 79.2 (12). HRMS (ESI): m/z calcd. for C₂₉H₃₁N₂OP⁺[M⁺]

454.21685; found 454.21659.

Borane Adduct of (1R,3R)-1-Phenyl-2-[(R)-1-phenylethyl]-N,N-

bis[(S)-1-phenylethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-

3(2H)-amine [(R_P)-24f·BH₃]: The compound was synthesized by

following the general procedure GP-Syn1 for ligand synthesis

starting from 1-((R)-phenyl{[(R)-1-phenylethyl]amino}methyl)-

naphthalen-2-ol (2.0 mmol, 1.0 equiv.) and (S)-bis[(S)-1-phenyl-

ethyl]amine (2.0 mmol, 1.0 equiv.). The product was obtained as a

colorless solid, yield 824.1 mg (1.33 mmol, 66 %). ¹H NMR

3

(400 MHz, CDCl₃): δ = 1.16 (d, J_H,H= 7.2 Hz, 6 H, CH₃), 1.76

3

(d, J_H,H= 7.1 Hz, 3 H, CH₃), 5.06 (dq, J_H,H= 7.1 Hz, J_H,P

=

3

7.0 Hz, 2 H, CH), 5.16 (m, 1 H, CH), 5.83 (d, J_H,P= 18.3 Hz, 1

H, CH), 6.80 (d, J_H,H= 8.5 Hz, 1 H, Ar), 6.96 (t, J_H,H= 7.4 Hz,

1 H, Ar), 7.05 (m, 10 H, Ar), 7.15 (m, 7 H, Ar), 7.30 (d, J_H,H

3

(1R,3S)-N,N-Diethyl-1-phenyl-2-[(R)-1-phenylethyl]-1H-naphtho-

[1,2-e][1,3,2]oxaza-phosphinine-3(2H)-amine [(S_P)-24a]: The com-

pound was synthesized from the borane adduct (0.5 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 190.9 mg

(0.42 mmol, 84%). ¹H NMR (400 MHz, CDCl₃): δ = 0.82 (t, ³J_H,H

3

=

3

7.4 Hz, 2 H, Ar), 7.45 (m, 3 H, Ar), 7.67 (d, J_H,H= 8.1 Hz, 1 H,

Ar), 7.75 (d, J_H,H= 8.5 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR

3

(100 MHz, CDCl₃): δ = 21.0 (d, J_C,P= 1.1 Hz, 2 ϫ CH₃), 21.5

(CH₃), 53.2 (d, J_C,P= 7.5 Hz, 2ϫCH), 55.4 (d, J_C,P= 17.3 Hz,

CH), 57.4 (d, J_C,P= 2.0 Hz, CH), 120.0 (d, J_C,P= 4.9 Hz, CH, Ar),

121.3 (CH, Ar), 124.2 (d, J_C,P= 6.2 Hz, C_q, Ar), 124.6 (CH, Ar),

126.6 (CH, Ar), 127.3 (2ϫCH, Ar), 127.5 (5ϫCH, Ar), 127.9 (CH,

Ar), 128.47 (3ϫCH, Ar), 128.49 (2ϫCH, Ar), 128.6 (2ϫCH, Ar),

129.03 (3ϫCH, Ar), 129.05 (3ϫCH, Ar), 129.14 (C_q, Ar), 129.7

(CH, Ar), 130.6 (C_q, Ar), 139.6 (d, J_C,P= 4.8 Hz, C_q, Ar), 141.5

3

= 7.0 Hz, 6 H, CH₃), 1.45 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 2.87 (m,

3

4 H, CH₂), 4.51 (dq, J_H,H= 7.0 Hz, J_H,P= 12.4 Hz, 1 H, CH),

5.87 (s, 1 H, CH), 7.13 (m, 2 H, Ar), 7.18–7.33 (m, 8 H, Ar), 7.42

3

(m, 1 H, Ar), 7.61 (m, 3 H, Ar), 7.72 (d, J_H,H= 8.1 Hz, 1 H, Ar),

3

7.84 (d, J_H,H= 8.6 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 14.0 (d, J_C,P= 3.0 Hz, 2ϫCH₃), 19.0 (d, J_C,P= 4.2 Hz,

CH₃), 38.2 (d, J_C,P= 19.9 Hz, 2ϫCH₂), 56.3 (d, J_C,P= 33.2 Hz,

CH), 56.6 (d, J_C,P= 8.3 Hz, CH), 120.9 (CH, Ar), 121.4 (CH, Ar),

123.6 (CH, Ar), 123.8 (d, J_C,P= 8.0 Hz, C_q, Ar), 126.4 (CH,

Ar),126.98 (CH, Ar), 127.02 (CH, Ar), 127.67 (CH, Ar), 127.70

(CH, Ar), 128.07 (2ϫCH, Ar), 128.21 (CH, Ar), 128.24 (CH, Ar),

128.31 (2ϫCH, Ar), 128.8 (CH, Ar), 128.9 (CH, Ar), 129.9 (C_q,

Ar), 130.0 (C_q, Ar), 141.9 (d, J_C,P= 3.8 Hz, C_q, Ar), 145.2 (C_q,

Ar), 147.6 (d, J_C,P= 5.8 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR

(162 MHz, CDCl₃): δ = 114.7 ppm. MS (EI): m/z (%) = 349.2 (32),

279.2 (22), 278.1 (16), 167.1 (34), 149.1 (100), 105.2 (26). HRMS

(ESI): m/z calcd. for C₂₉H₃₁N₂OP⁺[M⁺] 454.21685; found

454.21741.

(d, J_C,P= 4.4 Hz, 2ϫC_q, Ar), 142.2 (C_q, Ar), 149.0 (d, J_C,P

=

6.6 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

120.5 ppm.

Borane Adduct of (1R,3S)-N,N,1-Triphenyl-2-[(R)-1-phenylethyl]-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(S_P)-

24g·BH₃]: The compound was synthesized by following the general

procedure GP-Syn1 for ligand synthesis starting from 1-((R)-

phenyl{[(R)-1-phenylethyl]amino}methyl)naphthalen-2-ol

(2.0 mmol, 1.0 equiv.) and diphenylamine (2.0 mmol, 1.0 equiv.).

The product was obtained as a colorless solid, yield 607.4 mg

(1.08 mmol, 54%). ¹H NMR (400 MHz, CDCl₃): δ = 1.81 (d, ³J_H,H

3

= 7.0 Hz, 3 H, CH₃), 5.66 (dq, J_H,H= 6.9 Hz, J_H,P= 13.0 Hz, 1

3

H, CH), 5.70 (d, J_H,P= 15.1 Hz, 1 H, CH), 6.76 (m, 1 H, Ar),

6.82–6.92 (m, 6 H, Ar), 6.94–7.25 (m, 15 H, Ar), 7.39 (d, J_H,H

(1R,3R)-1-Phenyl-2-[(R)-1-phenylethyl]-3-(piperidin-1-yl)-2,3-di-

hydro-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine [(R_P)-24b]: The

3

=

7.7 Hz, 2 H, Ar), 7.66 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR compound was synthesized by following the general procedure GP-

(100 MHz, CDCl₃): δ = 19.5 (d, J_C,P= 4.5 Hz, CH₃), 54.5 (d, J_C,PSyn1 for ligand synthesis starting from 1-((R)-phenyl{[(R)-1-phen-

= 3.3 Hz, CH), 55.6 (d, J_C,P= 15.6 Hz, CH), 119.7 (d, J_C,P

6.2 Hz, CH, Ar), 120.8 (d, J_C,P= 8.7 Hz, C_q, Ar), 121.9 (CH, Ar),

=

ylethyl]amino}methyl)naphthalen-2-ol (0.5 mmol, 1.0 equiv.) and

piperidine (0.5 mmol, 1.0 equiv.), without purification via the bor-

Eur. J. Org. Chem. 2015, 6205–6230

www.eurjoc.org

6227

C. Schmitz, W. Leitner, G. Franciò

FULL PAPER

ane adduct. The product was obtained as a colorless solid, yield

(0.7 mmol) by following the general procedure GP-Syn4 for depro-

181.8 mg (0.39 mmol, 78%). ¹H NMR (300 MHz, CDCl₃): δ = 1.46 tection of ligands. The product was obtained as a colorless solid,

3

(d, J_H,H= 7.1 Hz, 3 H, CH₃), 1.52 (m, 6 H, CH₂), 2.87 (m, 4 H, yield 318.2 mg (0.62 mmol, 88%). [α]²_D⁵= 121.8 (c = 0.0275,

3

CH₂), 4.48 (dq, J_H,H= 7.1 Hz, J_H,P= 11.5 Hz, 1 H, CH), 5.56

CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 1.46 (d, ³J_H,H= 7.0 Hz,

3

(d, J_H,P= 6.8 Hz, 1 H, CH), 6.92–7.38 (m, 12 H, Ar), 7.51–7.71

3 H, CH₃), 1.69 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 1.74 (d, J_H,P=

(m, 4 H, Ar) ppm. ³¹P{¹H} NMR (121 MHz, CDCl₃): δ =

4.4 Hz, 3 H, NCH₃), 4.82 (dq, J_H,H= 7.0 Hz, J_H,P= 10.8 Hz, 1

3

135.4 ppm.

H, CH), 4.99 (dq, J_H,H= 7.0 Hz, J_H,P= 11.6 Hz, 1 H, CH), 5.71

(d, ³J_H,P= 7.3 Hz, 1 H, CH), 6.87 (m, 1 H, Ar), 6.96 (m, 2 H, Ar),

7.06 (m, 1 H, Ar), 7.11–7.36 (m, 13 H, Ar), 7.39 (m, 2 H, Ar), 7.66

(m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 18.2 (d,

(1R,3S)-N-Methyl-1-phenyl-N,2-bis[(R)-1-phenylethyl]-1H-naphtho-

[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(S_P)-24c]: The com-

pound was synthesized from the borane adduct (0.5 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 232.5 mg

(0.45 mmol, 90%). [α]²_D⁵= –338.3 (c = 0.2, CH₂Cl₂). ¹H NMR

J_C,P= 6.0 Hz, CH₃), 20.4 (d, J_C,P= 5.8 Hz, CH₃), 26.0 (d, J_C,P

4.2 Hz, NCH₃), 54.9 (d, J_C,P= 48.4 Hz, CH), 55.8 (d, J_C,P

=

2.8 Hz, CH), 57.1 (d, J_C,P= 40.5 Hz, CH), 121.2 (d, J_C,P= 3.2 Hz,

CH, Ar), 121.5 (CH, Ar), 123.5 (CH, Ar),124.3 (d, J_C,P= 6.1 Hz,

C_q, Ar), 126.0 (CH, Ar), 126.58 (CH, Ar), 126.63 (CH, Ar), 126.65

(CH, Ar), 127.28 (CH, Ar), 127.29 (CH, Ar), 127.41 (CH, Ar),

127.45 (CH, Ar), 127.8 (2ϫCH, Ar), 128.1 (4ϫCH, Ar), 128.2

(CH, Ar), 128.5 (2ϫCH, Ar), 128.7 (CH, Ar), 129.4 (C_q, Ar), 130.6

(C_q, Ar), 142.1 (d, J_C,P= 3.4 Hz, C_q, Ar), 142.9 (d, J_C,P= 5.7 Hz,

C_q, Ar), 144.1 (C_q, Ar), 150.5 (d, J_C,P= 3.9 Hz, C_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 133.5 ppm. MS (EI): m/z

(%) = 279.2 (24), 167.1 (49), 150.1 (12), 149.1 (100), 113.2 (11).

HRMS (ESI): m/z calcd. for C₃₄H₃₃N₂OP⁺[M⁺] 516.23250; found

516.23272.

3

(400 MHz, CDCl₃): δ = 1.41 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 1.42

(d, ³J_H,H= 7.1 Hz, 3 H, CH₃), 1.63 (d, ³J_H,P= 3.7 Hz, 3 H, NCH₃),

3

4.54 (dq, J_H,H= 7.0 Hz, J_H,P= 12.8 Hz, 1 H, CH), 4.80 (dq,

³J_H,H= 7.0 Hz, J_H,P= 10.1 Hz, 1 H, CH), 5.84 (s, 1 H, CH), 6.80

(d, J_H,H= 8.8 Hz, 1 H, Ar), 7.07 (m, 1 H, Ar), 7.13–7.39 (m, 14

3

H, Ar), 7.42 (d, J_H,H= 8.8 Hz, 1 H, Ar), 7.57 (d, J_H,H= 7.7 Hz,

3 H, Ar), 7.77 (d, J_H,H= 8.6 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR

3

(100 MHz, CDCl₃): δ = 17.5 (d, J_C,P= 9.4 Hz, CH₃), 19.0 (d, J_C,P

= 4.0 Hz, CH₃), 27.1 (d, J_C,P= 7.7 Hz, NCH₃), 55.5 (d, J_C,P

=

46.8 Hz, CH), 56.4 (d, J_C,P= 6.3 Hz, CH), 56.6 (d, J_C,P= 18.7 Hz,

CH), 120.2 (CH, Ar), 121.3 (CH, Ar), 123.6 (CH, Ar), 124.1 (d,

J_C,P= 8.0 Hz, C_q, Ar), 126.4 (CH, Ar), 126.7 (CH, Ar), 127.0 (CH,

Ar), 127.2 (CH, Ar), 127.55 (2ϫCH, Ar), 127.57 (CH, Ar), 127.59

(CH, Ar), 128.0 (2ϫCH, Ar), 128.2 (2ϫCH, Ar), 128.30 (CH,

Ar), 128.32 (CH, Ar), 128.37 (2ϫCH, Ar), 128.7 (CH, Ar), 129.2

(CH, Ar), 129.8 (C_q, Ar), 130.0 (C_q, Ar), 141.8 (d, J_C,P= 3.9 Hz,

C_q, Ar), 142.5 (C_q, Ar), 145.3 (C_q, Ar), 148.0 (d, J_C,P= 4.9 Hz, C_q,

Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 114.2 ppm. MS

(EI): m/z (%) = 518.2 (38), 517.2 (100), 354.2 (13), 233.1 (10).

HRMS (ESI): m/z calcd. for C₃₄H₃₄N₂OP⁺[M + H⁺] 517.24033;

found 517.23999.

(1R,3S)-N-Methyl-1-phenyl-2-[(R)-1-phenylethyl]-N-[(S)-1-phenyl-

ethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(S_P)-

24d]: The compound was synthesized from the borane adduct

(0.45 mmol) by following the general procedure GP-Syn4 for de-

protection of ligands. The product was obtained as a colorless so-

lid, yield 200.0 mg (0.39 mmol, 86 %). ¹H NMR (400 MHz,

3

CDCl₃): δ = 1.44 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 1.53 (d, J_H,H

=

3

7.0 Hz, 3 H, CH₃), 1.69 (d, J_H,P= 3.1 Hz, 3 H, NCH₃), 4.59 (dq,

³J_H,H= 7.0 Hz, J_H,P= 13.3 Hz, 1 H, CH), 4.79 (dq, J_H,H

=

3

7.0 Hz, J_H,P= 9.8 Hz, 1 H, CH), 5.92 (s, 1 H, CH), 7.11–7.44 (m,

3

17 H, Ar), 7.62 (d, J_H,H= 8.8 Hz, 1 H, Ar), 7.65 (d, J_H,H

=

3

(1R,3R)-N-Methyl-1-phenyl-N,2-bis[(R)-1-phenylethyl]-1H-naphtho-

[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-24c]: The com-

pound was synthesized from the borane adduct (0.7 mmol) by fol-

lowing the general procedure GP-Syn4 for deprotection of ligands.

The product was obtained as a colorless solid, yield 347.2 mg

(0.67 mmol, 96%). ¹H NMR (400 MHz, CDCl₃): δ = 1.52 (d, ³J_H,H

7.1 Hz, 1 H, Ar), 7.70 (d, J_H,H= 8.0 Hz, 1 H, Ar), 7.85 (d, J_H,H

= 8.5 Hz, 1 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

18.2 (d, J_C,P= 5.4 Hz, CH₃), 18.8 (d, J_C,P= 4.1 Hz, CH₃), 27.8 (d,

J_C,P= 7.9 Hz, NCH₃), 55.7 (d, J_C,P= 43.3 Hz, CH), 56.5 (d, J_C,P

= 3.6 Hz, CH), 56.6 (d, J_C,P= 28.3 Hz, CH), 120.4 (CH, Ar), 121.3

(CH, Ar), 123.6 (CH, Ar), 123.9 (d, J_C,P= 7.8 Hz, C_q, Ar), 126.4

(CH, Ar), 126.7 (CH, Ar), 127.0 (CH, Ar), 127.1 (CH, Ar), 127.3

(2ϫCH, Ar), 127.62 (CH, Ar), 127.64 (CH, Ar), 127.9 (2ϫCH,

Ar), 128.0 (2ϫCH, Ar), 128.20 (CH, Ar), 128.22 (CH, Ar), 128.3

(2ϫCH, Ar), 128.7 (CH, Ar), 129.2 (CH, Ar), 129.9 (C_q, Ar), 130.1

(C_q, Ar), 141.6 (d, J_C,P= 3.9 Hz, C_q, Ar), 142.7 (d, J_C,P= 11.0 Hz,

C_q, Ar), 145.2 (C_q, Ar), 147.9 (d, J_C,P= 4.2 Hz, C_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 112.1 ppm. MS (EI): m/z

(%) = 278.1 (15), 149.1 (14), 121.2 (14), 120.2 (100), 106.2 (10),

105.2 (70). HRMS (ESI): m/z calcd. for C₃₄H₃₃N₂OP⁺[M⁺]

516.23250; found 516.23274.

3

= 7.0 Hz, 3 H, CH₃), 1.64 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 1.80 (d,

3

³J_H,P= 4.9 Hz, 3 H, NCH₃), 4.79 (dq, J_H,H= 7.0 Hz, J_H,P

=

10.1 Hz, 1 H, CH), 5.01 (dq, ³J_H,H= 7.0 Hz, J_H,P= 11.6 Hz, 1 H,

CH), 5.68 (d, J_H,P= 7.5 Hz, 1 H, CH), 6.85 (m, 1 H, Ar), 6.94

3

(m, 2 H, Ar), 7.03 (m, 3 H, Ar), 7.12–7.37 (m, 13 H, Ar), 7.67 (m,

2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 18.6 (d, J_C,P

= 6.8 Hz, CH₃), 19.8 (d, J_C,P= 5.6 Hz, CH₃), 26.2 (NCH₃), 55.5

(d, J_C,P= 3.1 Hz, CH), 55.8 (d, J_C,P= 44.8 Hz, CH), 57.0 (d, J_C,P

= 40.9 Hz, CH), 121.1 (d, J_C,P= 3.1 Hz, CH, Ar), 121.5 (CH, Ar),

123.5 (CH, Ar),124.3 (d, J_C,P= 4.3 Hz, C_q, Ar), 126.0 (CH, Ar),

126.6 (2ϫCH, Ar), 126.7 (CH, Ar), 127.30 (CH, Ar), 127.36 (CH,

Ar), 127.41 (2ϫCH, Ar), 127.8 (2ϫCH, Ar), 128.03 (2ϫCH, Ar),

128.05 (2ϫCH, Ar), 128.14 (CH, Ar), 128.4 (2ϫCH, Ar), 128.7

(CH, Ar), 129.3 (C_q, Ar), 130.6 (C_q, Ar), 142.0 (d, J_C,P= 3.5 Hz,

C_q, Ar), 143.00 (C_q, Ar), 143.08 (C_q, Ar), 143.9 (C_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 134.2 ppm. MS (EI): m/z

(%) = 518.2 (14), 517.2 (100), 354.2 (34), 279.2 (11), 167.1 (24),

149.1 (43), 113.2. HRMS (ESI): m/z calcd. for C₃₄H₃₄N₂OP⁺[M +

H⁺] 517.24033; found 517.24012.

(1R,3R)-1-Phenyl-N,N,2-tris[(R)-1-phenylethyl]-1H-naphtho[1,2-e]-

[1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-24e]: The compound

was synthesized from the borane adduct (0.7 mmol) by following

the general procedure GP-Syn4 for deprotection of ligands. The

product was obtained as a colorless solid, yield 420.5 mg

(0.69 mmol, 99%). ¹H NMR (400 MHz, CDCl₃): δ = 1.44 (d, ³J_H,H

3

= 6.9 Hz, 6 H, CH₃), 1.88 (d, J_H,H= 7.0 Hz, 3 H, CH₃), 4.31 (dq,

3

³J_H,H= 7.0 Hz, J_H,P= 12.0 Hz, 2 H, CH), 5.02 (dq, J_H,H

=

3

6.9 Hz, J_H,P= 12.3 Hz, 1 H, CH), 5.76 (d, J_H,P= 8.4 Hz, 1 H,

(1R,3R)-N-Methyl-1-phenyl-2-[(R)-1-phenylethyl]-N-[(S)-1-phenyl- CH), 6.78 (m, 1 H, Ar), 6.86 (m, 2 H, Ar), 6.97 (m, 1 H, Ar), 7.00–

ethyl]-1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-

24d]: The compound was synthesized from the borane adduct

3

7.10 (m, 13 H, Ar), 7.16 (m, 2 H, Ar), 7.24 (d, J_H,H= 8.8 Hz, 1

H, Ar), 7.31 (m, 4 H, Ar), 7.62 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR

6228

www.eurjoc.org

Eur. J. Org. Chem. 2015, 6205–6230

P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands

[6]

[7]

a) J. Bayardon, S. Jugé, in: Phosphorus(III) Ligands, in:

Homogeneous Catalysis (Eds.: P. C. J. Kamer, P. W. N. M.

van Leeuwen), Wiley, 2012, p. 355–389; b) P-Stereogenic Li-

gands in Enantioselective Catalysis (Ed.: A. Grabulosa), RSC

Publishing, Cambridge, UK, 2011; c) J. S. Harvey, V. Gouvern-

eur, Chem. Commun. 2010, 46, 7477; d) M. J. Johansson, N. C.

Kann, Mini-Rev. Org. Chem. 2004, 1, 233–247.

For instance, heteroatom-substituents at the phosphorus atom

can increase the inversion barrier for the epimerization of

P-stereogenic center compounds. See for examples: a) R. D.

Beachler, K. Mislow, J. Am. Chem. Soc. 1970, 92, 3090; b) A.

Rauk, J. D. Andose, W. G. Frick, R. Tang, K. Mislow, J. Am.

Chem. Soc. 1971, 93, 6507.

(100 MHz, CDCl₃): δ = 21.0 (d, J_C,P= 5.1 Hz, CH₃), 22.1 (br.

CH₃), 22.2 (CH₃), 52.4 (d, J_C,P= 11.8 Hz, 2ϫCH), 56.2 (d, J_C,P

=

3.0 Hz, CH), 56.4 (d, J_C,P= 47.9 Hz, CH), 121.0 (d, J_C,P= 3.0 Hz,

CH, Ar), 121.2 (CH, Ar), 123.4 (CH, Ar), 125.7 (CH, Ar), 125.9

(2ϫCH, Ar), 126.0 (d, J_C,P= 5.4 Hz, C_q, Ar), 126.5 (CH, Ar),

126.7 (CH, Ar), 127.3 (4ϫCH, Ar), 127.39 (CH, Ar), 127.45 (CH,

Ar), 127.54 (2 ϫ CH, Ar), 127.8 (4 ϫ CH, Ar), 128.0 (CH, Ar),

128.1 (2ϫCH, Ar), 128.3 (2ϫCH, Ar), 128.4 (CH, Ar), 129.3 (C_q,

Ar), 130.0 (C_q, Ar), 141.6 (d, J_C,P= 2.8 Hz, C_q, Ar), 143.7 (br.,

2ϫC_q, Ar), 143.8 (C_q, Ar), 151.2 (d, J_C,P= 1.6 Hz, C_q, Ar) ppm.

³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 137.4 ppm. MS (EI): m/z

(%) = 501.5 (19), 278.3 (16), 231.3 (10), 210.4 (39), 200.3 (10), 106.3

(26), 105.3 (100), 79.3 (11), 77.3 (14). HRMS (ESI): m/z calcd. for

C₄₁H₄₀N₂OP⁺[M + H⁺] 607.28728; found 607.29012.

[8]

Privileged Chiral Ligands and Catalysts (Ed.: Q.-L. Zhou),

Wiley-VCH, Weinheim, Germany, 2011.

[9]

A. J. Minnaard, B. L. Feringa, L. Lefort, J. G. De Vries, Acc.

Chem. Res. 2007, 40, 1267.

a) A. H. M. De Vries, A. Meetsma, B. L. Feringa, Angew.

Chem. Int. Ed. Engl. 1996, 35, 2374; Angew. Chem. 1996, 108,

2526; b) M. van den Berg, A. J. Minnard, E. P. Schudde, J.

van Esch, A. H. M. de Vries, J. G. de Vries, B. L. Feringa, J.

Am. Chem. Soc. 2000, 122, 11539.

For reviews on phosphoramidites, see: a) J. F. Teichert, B. L.

Feringa, Angew. Chem. Int. Ed. 2010, 49, 2486; Angew. Chem.

2010, 122, 2538; b) J. Ansell, M. Wills, Chem. Soc. Rev. 2002,

31, 259; c) L. Lefort, J. G. de Vries, in: Phosphorus(III) Ligands

in Homogeneous Catalysis (Eds.: P. C. J. Kamer, P. W. N. M.

van Leeuwen), Wiley, 2012, p. 133–158; d) D. J. Ager, A. H. M.

de Vries, J. G. de Vries, Platinum Met. Rev. 2006, 50, 54; e) M.

van den Berg, B. L. Feringa, A. J. Minnaard, in: Handbook of

Homogeneous Hydrogenation (Eds.: J. G. de Vries, C. J. Elsev-

ier), Wiley-VCH, Weinheim, Germany 2007, p. 995–1027.

E. B. Benetsky, S. V. Zheglov, T. B. Grishina, F. Z. Macaev,

L. P. Bet, V. A. Davankov, K. N. Gavrilov, Tetrahedron Lett.

2007, 48, 8326.

(1R,3R)-1-Phenyl-2-[(R)-1-phenylethyl]-N,N-bis[(S)-1-phenylethyl]-

1H-naphtho[1,2-e][1,3,2]oxazaphosphinine-3(2H)-amine [(R_P)-24f]:

The compound was synthesized from the borane adduct (0.7 mmol)

by following the general procedure GP-Syn4 for deprotection of

ligands. The product was obtained as a colorless solid, yield

[10]

412.0 mg (0.68 mmol, 97%). [α]²_D⁵= –218.7 (c = 0.5, CH₂Cl₂). H

1

[11]

3

NMR (400 MHz, CDCl₃): δ = 1.53 (d, J_H,H= 7.1 Hz, 3 H, CH₃),

3

1.64 (d, J_H,H= 7.0 Hz, 6 H, CH₃), 4.25 (dq, J_H,H= 7.0 Hz, J_H,P

3

= 11.3 Hz, 1 H, CH), 4.37 (dq, J_H,H= 7.0 Hz, J_H,P= 11.9 Hz, 2

H, CH), 5.73 (d, ³J_H,P= 9.4 Hz, 1 H, CH), 6.76 (m, 1 H, Ar), 6.82

(m, 2 H, Ar), 6.87–7.16 (m, 17 H, Ar), 7.20 (m, 1 H, Ar), 7.25 (m,

3 H, Ar), 7.60 (m, 2 H, Ar) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 20.9 (d, J_C,P= 6.0 Hz, CH₃), 22.5 (d, J_C,P= 10.4 Hz,

2ϫCH₃), 52.7 (d, J_C,P= 10.9 Hz, 2ϫCH), 56.23 (d, J_C,P

=

40.0 Hz, CH), 56.29 (d, J_C,P= 2.4 Hz, CH), 121.0 (d, J_C,P= 2.4 Hz,

CH, Ar), 121.2 (CH, Ar), 123.5 (CH, Ar), 125.8 (CH, Ar), 126.3

(2ϫCH, Ar), 126.4 (d, J_C,P= 5.6 Hz, C_q, Ar), 126.5 (CH, Ar),

126.7 (CH, Ar), 127.33 (CH, Ar), 127.39 (CH, Ar), 127.43 (4ϫCH,

Ar), 127.6 (2ϫCH, Ar), 128.03 (2ϫCH, Ar), 128.05 (2ϫCH, Ar),

128.08 (2ϫCH, Ar), 128.11 (CH, Ar), 128.58 (CH, Ar), 128.62

[12]

[13]

[14]

For a recent contribution from our group, see: C. Schmitz, W.

Leitner, G. Franciò, Chem. Eur. J. 2015, 21, 10969.

a) M. T. Reetz, J. A. Ma, R. Goddard, Angew. Chem. Int. Ed.

2005, 44, 412; Angew. Chem. 2005, 117, 416; b) K. N. Gavrilov,

E. B. Benetsky, V. E. Boyko, E. A. Rastorguev, V. A. Davankov,

B. Schaffner, A. Börner, Chirality 2010, 22, 844.

(2ϫCH, Ar), 129.5 (C_q, Ar), 129.9 (C_q, Ar), 142.1 (d, J_C,P

=

2.0 Hz, C_q, Ar), 143.9 (C_q, Ar), 144.2 (2ϫC_q, Ar), 151.1 (d, J_C,P

= 1.8 Hz, C_q, Ar) ppm. ³¹P{¹H} NMR (162 MHz, CDCl₃): δ =

144.8 ppm. MS (EI): m/z (%) = 279.2 (18), 210.2 (42), 167.1 (34),

149.1 (100), 106.2 (29), 105.2 (44), 86.2 (27). HRMS (ESI): m/z

calcd. for C₄₁H₃₉N₂OP⁺[M⁺] 606.27945; found 606.27935.

[15]

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S. D. Pastor, J. L. Hyun, P. A. Odorisio, R. K. Rodebaugh, J.

Am. Chem. Soc. 1988, 110, 6547.

a) A. I. Polosukhin, O. G. Bondarev, S. E. Lyubimov, A. A.

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47, 9013.

Acknowledgments

[17]

[18]

The authors thank Julia Wurlitzer and Hannelore Eschmann for

GC and HPLC measurements, Katharina Holthusen for valuable

experimental assistance, the group of Prof. Ulli Englert for the ac-

quisition of X-ray diffraction raw data, Dr. Markus Hölscher for

crystal structure analysis, and Dr. Kylie Luska for a critical reading

of this manuscript.

For phosphorodiamidites synthesized from C₁-symmetric di-

amines and alcohols, see for example: a) K. N. Gavrilov, V. N.

Tsarev, S. E. Lyubimov, A. A. Shyryaev, S. V. Zheglov, O. G.

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Kalinin, Mendeleev Commun. 2003, 134; b) V. N. Tsarev, S. E.

Lyubimov, A. A. Shiryaev, S. V. Zheglov, O. G. Bondarev, V. A.

Davankov, A. A. Kabro, S. K. Moiseev, V. N. Kalinin, K. N.

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Zheglov, E. A. Rastorguev, P. V. Petrovskii, F. Z. Macaev, V. A.

Davankov, Tetrahedron: Asymmetry 2007, 18, 2557; g) K. N.

Gavrilov, S. E. Lyubimov, O. G. Bondarev, M. G. Maksimova,

S. V. Zheglov, P. V. Petrovskii, V. A. Davankov, M. T. Reetz,

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C. Schmitz, W. Leitner, G. Franciò

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methods gave reproducible results in terms of yield and dia-

stereomeric purity. Finally, the multiple recrystallization of the

crude mixture or diastereomerically enriched fractions from

boiling toluene or acetonitrile afforded pure (R,S)-19.

[34] Since the reaction in THF and with triethylamine as base pro-

vided only a small amount of the R_Pepimer, other solvents

(CH₂Cl₂, toluene) and bases (n-butyllithium) were tested. How-

ever, no significant differences in the preferred configuration at

the phosphorus atom ore side reactions were observed.

[35] The yields reported in the experimental part always refer to the

synthetic procedure leading to maximum yield and may not be

coincident with the values reported here.

[36] It is important to note that the change in CIP priority from

the Cl- to OMe-substituent results in the same stereodescriptor

for the phosphorus atom (S_P) although the relative spatial ar-

rangement is inverted.

[37] Here, the N-atom of NPh₂has a higher CIP priority compared

with the N-atom in the Betti base backbone. This leads to a

change in the CIP nomenclature of the configuration of the

P-atom to (S_P). The relative spatial orientation of the NPh₂

substituent is the same as for the other amine-substituents of

the ligands with R_Pconfiguration.

[38] It should be noted that, whereas dichloroaminophosphines can

be directly generated from PCl₃and the corresponding amine,

an analogous in situ approach for the synthesis of dichloro-

phosphite from PCl₃and an alcohol leads to significant

amounts of chlorophosphite and phosphite even by slow

alcohol addition and under high dilution. Pure dichlorophos-

phite are usually synthesized through a two-step procedure

from the condensation of, for example, ClP(NEt₂)₂with an

alcohol followed by substitution of the amino moieties via an-

hydrous HCl.

[19] The combination of amino alcohols with carbon fragments was

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be found in: a) P. Cros, G. Buono, G. Peifer, D. Denis, A. Mor-

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Stingl, H. Thümler, W. Saak, D. Haase, S. Pohl, S. Jugé, J.

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sufficient purity for catalytic experiments by using the same

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Received: June 10, 2015

Published Online: August 12, 2015

6230

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Eur. J. Org. Chem. 2015, 6205–6230

Article Doi

Synthesis of P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis

DOI: 10.1002/ejoc.201500767

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