P-stereogenic pinene-derived phosphoramidites and their use in copper-catalyzed conjugate additions

Article abstract of DOI:10.1002/ejic.201000946

New P-stereogenic phosphoramidites based on a (-)-pinane framework were synthesized and investigated by NMR spectroscopic methods and single-crystal X-ray structural analysis. The reaction between cis-pinandiol 2 and N,N-dialkylphosphoramidous dichlorides

Full text of DOI:10.1002/ejic.201000946

FULL PAPER
DOI: 10.1002/ejic.201000946
P-Stereogenic Pinene-Derived Phosphoramidites and Their Use in Copper-
Catalyzed Conjugate Additions
Dennis Hobuß,[a] Angelika Baro,[a] Kirill V. Axenov,[a] Sabine Laschat,*[a] and
Wolfgang Frey[a]
Dedicated to Professor Henning Hopf on the occasion of his 70th birthday
Keywords: Asymmetric catalysis / Copper / Phosphoramidite / Chirality / Conjugate addition
New P-stereogenic phosphoramidites based on a (–)-pinane
framework were synthesized and investigated by NMR spec-
troscopic methods and single-crystal X-ray structural analy-
sis. The reaction between cis-pinandiol 2 and N,N-dialkyl-
with Et2NH at elevated temperature and the obtained free
phosphoramidite ligands were used for catalytic enantiose-
lective conjugate addition reactions. As substrates, a series
of cyclic and acyclic enones was employed and addition was
phosphoramidous dichlorides, followed by protection with the carried out with Et2Zn in the presence of catalytic amounts
BH3·THF adduct, afforded diastereomeric mixtures of PS and
PR BH3–phosphoramidite complexes. After separation by col-
umn chromatography, these stereoisomers were obtained in
a pure form. The BH3 group was further cleaved by treatment
of CuI thiophenecarboxylate (CuTC) and a phosphoramidite
ligand. The results revealed that the configuration of the
phosphorus center controls the configuration of the newly
formed stereogenic center of the β-alkylated ketones.
to hydroformylation,[7] allylic substitution,[4,8a] arylation,[8b]
and hydrogenation of ketones and dehydroamino acids.[5,9]
To the best of our knowledge, conjugate additions have not
been considered so far. In this context, we focused in this
contribution on the synthesis of the P-stereogenic phos-
phoramidite ligands and their application in conjugate ad-
dition reactions. For such purpose, we anticipated that (–)-
α-pinene 1 might be a suitable scaffold for the synthesis of
P-chiral phosphoramidites 6 and 7 (Scheme 1). Previously,
we have already shown that (–)-α-pinene 1 could be readily
converted into the corresponding bisphosphinites through
cis-diol 2.[10,11] In this work we used cis-diol 2 as a starting
material for preparation of new phosphoramidites 6 and 7.
The synthetic details, the structure of protected new P-chi-
ral phosphoramidites, and preliminary results, with regard
to the application of the new ligands in conjugate addition
reactions, are reported below.
Introduction
The enantioselective Cu-catalyzed conjugate addition of
organozinc and organomagnesium reagents to α,β-unsatu-
rated carbonyl compounds has been elaborated into a
powerful tool in synthetic organic chemistry.[1] Besides a
variety of different P ligands, which have been employed for
this reaction, phosphoramidites in particular have received
great interest due to their enhanced stability and high
enantioselectivity.[2,3] Both the diol moiety and the second-
ary amine substituent of the phosphoramidite allow the in-
troduction of chirality. Consequently, the stereochemical
control, which is provided by different chiral units of a
phosphoramidite ligand core, on the steric outcome of con-
jugate addition reactions can be studied in detail. Further-
more, it has been independently shown by Gavrilov and
Gais et al.,[4] and Reetz et al.[5] that the use of unsymmetri-
cal chiral diamines and chiral alcohols or, alternatively, the
use of unsymmetrical chiral diols and secondary amines re-
sulted in the diastereoselective formation of phosphoramid-
ites with P-stereogenic centers.[6] However, surprisingly little
information is available about the use of P-stereogenic li-
gands in asymmetric catalysis. Most work has been devoted
Results and Discussion
Synthesis and Structure of P-Chiral Phosphoramidites
As shown in Scheme 1, (–)-α-pinene 1 was submitted to
dihydroxylation according to our previously published
method[10] to give diol 2 with cis orientation of the neighbor
hydroxy groups. The phosphoramino function was intro-
duced into the cis-pinandiol framework through two dif-
ferent synthetic pathways. In the first approach, compound
[a] Institut für Organische Chemie, Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49-711-685-64285
E-mail: sabine.laschat@oc.uni-stuttgart.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201000946.
384
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P-Stereogenic Pinene-Derived Phosphoramidites
Scheme 1.
2 was treated with PCl3 in the presence of Et3N,[12] which and 7e always showed very close Rf values and could not be
led to the formation of chlorophosphite 3. This product was separated from each other by preparative chromatography
used without further isolation and treated at low tempera- methods.
ture in THF with a series of dialkylamines 4c,d,f in the pres-
X-ray crystal-structure analysis of single crystals ob-
ence of Et3N. After subsequent reaction with BH3·THF, the tained from the products 6b and 7d allowed the deter-
raw products were subjected to chromatography on silica mination of the absolute configuration around the P-
gel, selectively giving the PS-configured phosphoramidite– stereogenic center in 6 and 7 (Figures 1 and 2).[14]
borane complexes 6c,d,f (see the Supporting Information).
However, the overall yields obtained by this route were
quite low. Possibly, due to the presence of the bulky (–)-
pinane moiety, the phosphorus center in 3 is barely access-
ible for nucleophilic substitution reactions. To increase the
productivity and get access to PR-stereoisomers 7, we
looked for another synthetic procedure. Alternatively, a
series of (dialkylamino)phosphorus dichlorides 5a–e was
prepared by the reaction between an excess amount of di-
alkylamines 4a–e and phosphorus trichloride, following a
procedure by van Leeuwen and co-workers.[13] The treat-
ment of cis-diol 2 with N,N-dialkylphosphoramidous di-
chlorides 5a–e in THF at temperatures between 0 and 25 °C
and subsequent protection with BH3·THF led to the new
phosphoramidite–borane products as mixtures of dia-
stereomers 6 and 7 (with a ratio of 1:1, Scheme 1). A pre-
Figure 1. Structure of compound 6b in the solid state. View along
the five-membered ring system, flat conformation [for a better over-
view, anisotropic displacement parameters with 35% probability
and without disordered ethyl function (C13, C14)].
parative separation of diastereomers 6 and 7 was achieved
by means of column chromatography on silica gel, and
compounds 6a–d and 7a–d were isolated in a pure state as
colorless crystalline solids. The only exceptions were the
(S,S)-bis(α-methylbenzyl)amine-derived ligands 6e and 7e.
The BH3–phosphoramidite complex 6b features a 1,2-di-
For the synthesis of 6e and 7e, cis-diol 2 was deprotonated oxo-substituted (–)-pinane framework with the oxygen
with an excess amount of nBuLi. Subsequent reaction with atoms occupying positions cis to each other (Figure 1). The
5e, followed by protection with BH3·THF, gave a dia- oxygen atoms are connected with the (–)-pinane framework
stereomeric mixture of 6e and 7e (ratio of isomers 1:1.6, [C1–O2: 1.519(6) Å, C2–O1: 1.529(6) Å]. In addition, they
isolated yield 65%). Unfortunately, phosphoramidites 6e are bonded with the same phosphorus center in a chelate
Eur. J. Inorg. Chem. 2011, 384–392
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385

D. Hobuß, A. Baro, K. V. Axenov, S. Laschat, W. Frey
FULL PAPER
bulky (–)-pinane core. The closest calculated H(piperidino)···
H[(–)-pinane] distance is 2.03 Å, which is much shorter
than that found for derivative 6b (see above). The strong
steric repulsion between these large groups leads to a con-
siderable puckering of the [C2O2P] ring in 7c. The puckering
angle, defined as above for 6b isomer, is 19.28°. The [C2O2P]
ring adopts an envelope-like conformation. The C6–O1–P1
and the C11–O2–P1 angles are 112.89(16) and 113.69(18)°,
respectively. The P1–N1 bond and the B1–P1 connection
have typical values of 1.620(3) and 1.898(4) Å, respectively.
The piperidine unit, connected to the phosphorus center,
has a chair conformation with diastereotopic hydrogen
atoms placed in axial and equatorial positions of the piperi-
dine ring.
Figure 2. Structure of phosphoramidite 7d in the solid state. View
along the five-membered ring system, envelope conformation, O1
out-of-plane.
Table 1. Selected structural parameters of BH3–phosphoramidite
complexes 6b and 7d.[a]
6b
7d
6b
7d
fashion [O1–P1: 1.597(3) Å, O2–P1: 1.595(3) Å]. The phos-
phorus atom, both oxygen atoms, and the C1 and C2
carbon atoms create the five-membered chelate [C2O2P]
ring anellated with the (–)-pinane core through the C1 and
C2 positions. The [C2O2P] ring has an exo orientation,
whereas the methyl substituent at C1 atom is directed endo
relative to the (–)-pinane core [C1–C10: 1.515(5) Å]. In ad-
dition to the two oxygen atoms, the phosphorus center is
connected with a secondary diethylamino group [P1–N1:
1.633(5) Å] and with a BH3 moiety by a strong dative do-
C1–O2 1.465(4) 1.466(3) C1–C2–O1
C2–O1 1.434(5) 1.450(4) C2–C1–O2
P1–O1 1.597(3) 1.612(2) C1–O2–P1
P1–O2 1.595(3) 1.606(2) C2–O1–P1
107.3(3)
104.9(3)
115.7(2) 112.89(16)
115.6(2) 113.69(18)
95.92(15) 95.82(11)
113.3(3) 114.53(19)
106.8(2) 105.33(16)
107.4(2)
104.5(2)
P1–B1
1.892(6) 1.898(4) O1–P1–O2
P1–N1 1.633(5) 1.620(3) B1–P1–N1
C1–C10 1.515(5) 1.519(4) N1–P1–O1
[a] Bond lengths given in Å and angles in °. Atom numbering ac-
cording to 6b.
The PS-configured complex 6b features a typical 1H
nor–acceptor bond [P1–B1: 1.892(6) Å]. The phosphorus NMR spectroscopic A3B2 spin system for the –NEt2 group
center in 6b is tetracoordinated (trigonal pyramidal) and at δH = 1.12 and 3.15 ppm; three singlets for (–)-pinane
has an S configuration with BH3– and –NEt2 substituents methyl substituents at δH = 0.87, 1.30, and 1.56 ppm; mul-
oriented exo and endo relative to the (–)-pinanephosphite tiple signals for CH and CH2 protons of the (–)-pinane core
core [enantiopol parameter is 0.0(2)]. In this S configura- at δH = 1.94, 1.98, 2.10, 2.17, 2.24, 2.40, and 4.58 ppm (total
tion the steric repulsive interactions between the bulky 7H of relative intensity). The 31P NMR spectroscopic signal
(–)-pinane and the Et2N– units are minimized, as these of 6b appeared at low field at δP = 144.8 ppm. In the 13C
2,3
moieties are placed far from each other with a closest calcu- NMR spectra, all possible
J
couplings between carbon
P,C
lated H(Et2N)···H[(–)-pinane] distance of 2.29 Å. The atoms of the (–)-pinane core, the –NEt2 group, and the
[C2O2P] ring is almost flat. The puckering angle between phosphorus center have been detected (see the Exp. Section
2
two planes, defined by O2–P1–O1 atoms and O2–C1–C2– and Supporting Information). In this row, the JP,C cou-
O1 atoms, respectively, is 1.56°. The C1–O2–P1 and the C2– plings between carbon atoms of the [C2O2P] ring and the
O1–P1 angles are 115.7(2) and 115.6(2)°, respectively. Based phosphorus center appeared to be essential to recognize the
on these observations, sp2 hybridization of oxygen atoms absolute configuration at the P-stereogenic center in com-
could be proposed, with one of the free electron pairs occu- pounds 6 and 7 (see below). For complex 6b, they are 4.5
pying a nonhybridized p orbital, which is oriented perpen- and 7.2 Hz, respectively. Whereas the PR-configured isomer
1
dicular to the [C2O2P] cycle. Electron density from this p 7b shows an H NMR spectrum analogous to 6b (see the
orbital could easily be donated through π–π interactions to Supporting Information), the 31P NMR spectroscopic sig-
empty d orbitals of the same symmetry on the phosphorus nal of 7b is noticeably shifted upfield to δP = 142.8 ppm.
center (according to the “backdonation” concept), thus sta- Moreover, in isomer 7b, the absence of the characteristic
bilizing the structure of complex 6b.
2JP,C couplings within the [C2O2P] ring has been detected.
The structural features of the piperidino-substituted Based on these observations, it could in general be con-
BH3–phosphoramidite complex 7d are rather similar to cluded that BH3–phosphoramidite complexes, which dis-
those of the related compound 6b (Table 1). Compound 7d play a 31P NMR spectroscopic signal at low field and dis-
2
features the (–)-pinane core with the [C2O2P] ring anellated tinct JP,C couplings in the 13C NMR spectra between the
in an exo position. In contrast to analogue 6b, the phos- carbon atoms of the (–)-pinane core and the phosphorus
phorus center in 7d has the R configuration with the exo- center, are the PS stereoisomers 6 (Figure 3). Conversely, for
positioned piperidine substituent [observed enantiopol the PR analogues 7, upfield-shifted 31P NMR spectroscopic
2
parameter –0.07(16)] (Figure 2). The exo-oriented large resonances together with absence of detectable JP,C
piperidine group appeared to be in a close vicinity of the couplings (except those between the amine unit and P-
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P-Stereogenic Pinene-Derived Phosphoramidites
stereogenic center) in the 13C NMR spectra could be ex- 151.8 ppm. The same compound 8c was then treated with
pected (Figure 3).[15] To verify this statement, we carefully the BH3·THF complex under typical conditions (THF,
analyzed the pair of isomers 6d and 7d, for which com- 0 °C, 2 h). After workup, the product of the reaction dis-
pound 7d had the assigned PR configuration, determined played a 1H NMR spectrum and optical rotation angle
from single-crystal X-ray structural studies (see above). identical to those recorded independently for PS-configured
Both compounds behaved as expected. They showed very BH3–phosphoramidite complex 6c. The observed 31P NMR
similar 1H NMR spectroscopic features (see the Supporting spectroscopic shifts of the product and the starting complex
Information). The 31P NMR spectroscopic signal of PR- 6c were the same (see Scheme 2). This means that during
configured complex 7d was shifted upfield relative to that the deprotection–protection sequence the configuration of
of the PS-configured analogue 6d (δP = 142.3 ppm for 7d the P-stereogenic center remained unchanged.
vs. δP = 146.0 ppm for 6d). Whereas 2JP,C couplings between
the carbon atoms of the (–)-pinane core and the phos-
Enantioselective Conjugate Addition Reactions
phorus center were observed for complex 6d (4.6 and
2
7.5 Hz, respectively), these JP,C couplings were not de-
It has been previously shown that phosphoramidite li-
gands provide high activity and stereoselectivity in conju-
gate addition reactions.[2] The influence of both the struc-
ture of the ligand core and nature of the amino function on
the steric outcome of the reaction has been investigated in
detail.[3] The first phosphoramidite ligands employed for
catalytic conjugate addition were based on a chiral bi-
naphthol core with attached achiral dialkylamino substitu-
ent.[2l] They showed high conversion (more than 80%) and
moderate up to high enantioselectivity in 1,4-addition of
Et2Zn to cyclohexenone (up to 60% ee) and chalcone (up to
81% ee) substrates.[12] The modification with a chiral bis(α-
methylbenzyl)amino substituent was highly active and se-
lective in 1,4-addition reactions of Et2Zn to cyclohexenone,
but selectivity decreased in the case of cycloheptenone
(53% ee).[17] Lately, new flexible biphenol-derived ligands
have been designed and used for Cu-mediated conjugate ad-
dition of Et2Zn to a number of cyclic and acyclic activated
unsaturated substrates with very good yields and selectivi-
ties.[18] In our preliminary experiments, we mainly focused
on studying the influence of stereochemical configuration
around the P-stereogenic center of the phosphoramidite li-
gand on the selectivity of the conjugate addition. To find
optimum conditions for the catalytic reactions, cyclo-
hexenone 10a was treated with diethylzinc in the presence
of ligand 9b (10 mol-%) and various copper precursors
(5 mol-%) in different solvents (Scheme 3).[19]
tected for PR-configured isomer 7d. Having a clear assign-
ment for the PS-configured diastereomer 6b and the PR-
configured diastereomer 7d, the absolute configuration of
the P-stereogenic center for the series of complexes 6a–e
and 7a–d was determined on the basis of the 13C and 31P
NMR spectroscopic data.
Figure 3. 13C and 31P NMR spectroscopic features of PS-stereoiso-
mers 6 and PR-stereoisomers 7.
The BH3–phosphoramidite complexes were relatively
stable and could easily be handled. However, for catalytic
purposes they had to be deprotected prior to use. In a typi-
cal procedure, a BH3–phosphoramidite complex was depro-
tected by heating in Et2NH, followed by removal of all vola-
tiles under high vacuum.[16] As a free phosphoramidite li-
gand is released during this process, there is potentially the
possibility of inversion or even racemization of the P-
stereogenic center under conditions of prolonged heating.
To examine the result of the deprotection, we carried out a
series of experiments. The PS-configured BH3–phos-
phoramidite complex 6c (δP = 144.1 ppm) was heated in
Et2NH at 65 °C for 12 h. An excess amount of Et2NH and
volatile byproducts were removed under high vacuum. The
residue, which consisted of the free ligand 8c, was investi-
gated by means of 31P NMR spectroscopy. The compound
8c featured a 31P NMR spectroscopic singlet at δP
=
Scheme 3.
The obtained enantioselectivities were strongly depend-
ent on the copper source and to a lesser extent on the sol-
vent (for details, see the Supporting Information). Whereas
Cu(OTf)2 worked best in toluene (17% ee) relative to Et2O
Scheme 2.
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D. Hobuß, A. Baro, K. V. Axenov, S. Laschat, W. Frey
Table 2. Conjugate addition of Et2Zn to enones 10 and 12 in the presence of ligands 8, 9, and CuTC.[a]
FULL PAPER
Entry Enone Ligand
R
Configuration at P center
Product
Conversion [%][b] ee [%][c] Configuration of product[d]
1
2
3
4
5
6
7
8
10a
10a
10a
10a
10b
10b
10b
10b
12
8b
9b
8c
9c
8b
9b
8c
9c
8b
9b
8c
9c
Et
Et
iPr
iPr
Et
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
11a
11a
11a
11a
11b
11b
11b
11b
13
100
100
100
100
100
100
85
88
43
96
90
3
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(–)
(–)
(–)
(–)
36
12
21
26
23
33
33
2
Et
iPr
iPr
Et
Et
iPr
iPr
9
10
11
12
12
13
27
11
50
12
12
13
13
83
[a] Reaction conditions: substrate (1 equiv.), Et2Zn (1.5 equiv.), CuTC (5 mol-%), 8 or 9 (10 mol-%), toluene, –20 °C, 3 h. [b] Determined
by GC (undecane as an internal standard). [c] Determined by GC or HPLC on a chiral phase (see details in the Supporting Information).
[d] Determined by a comparison of observed optical rotation data with literature.
(8% ee) and CH2Cl2 (7% ee), Cu(OAc)2 yielded moderate enantioselectivity of conjugate addition within a series of
enantioselectivity (21% ee) only in Et2O. By using copper(I) PS- and PR-configured phosphoramidite ligands 8b,c and
thiophenecarboxylate (CuTC), the selectivity could be in- 9b,c. When more flexible cycloheptenone substrate 10b was
creased in all solvents. The most pronounced effect was ob- employed, both series of phosphoramidites 8b,c and 9b,c
served in toluene, in which higher ee values (34% ee), rela- gave very similar moderate enantioselectivity values, regard-
tive to Et2O (18% ee) or CH2Cl2 (17% ee), were obtained. less of the configuration around the P-stereogenic center
Thus, copper(I) thiophenecarboxylate and toluene were (around 23–26% ee for the 8b/9b pair and 33% ee for the
chosen for the following catalytic reactions.
8c/9c pair). In conjugate addition of Et2Zn to cyclic enones
Prior to the catalytic reaction, BH3–phosphoramidite 10a,b, PS-configured ligands 8a–c gave mixtures with a pre-
complexes 6a–d and 7a–d were deprotected in a manner al- dominant content of R-alkylated ketone, whereas the S-alk-
ready used for the generation of ligand 8c (heating in ylated ketone was the major enantiomer provided by PR-
Et2NH at 65 °C for 12 h; see above and Scheme 4).[16] In configured ligands 9a–c (see Table 2).
this way, a series of PS- and PR-configured ligands 8a–d
and 9a–d, respectively, have been obtained and immediately
employed for further catalytic experiments. In a general re-
action setup, we used CuTC (5 mol-%), ligand 8 or 9
(10 mol-%), enone substrate (1 equiv.), and ZnEt2
(1.5 equiv.) alkylation reagent. The reaction was carried out
at –20 °C for 3 h. Selected obtained results are summarized
in Table 2 and Scheme 4. Regardless of the enone substrate,
the ligands 8d and 9d, which bore bulky piperidine groups,
did not show high enantioselectivity in conjugate addition
of ZnEt2, albeit in most of the runs high yields of alkylated
products were obtained. The same behavior was observed
for NMe2-substituted ligand 9a. Possibly, these ligands were
too labile under the applied reaction conditions. The phos-
phoramidites 8b and 9b, 8c and 9c, which have Et2N– and
iPr2N– functionalities, respectively, showed different results.
In the conjugate addition of Et2Zn to the cyclic enone 10a
as well as to the acyclic substrate 12, PS-configured ligands
8b,c displayed poor enantioselectivities up to 12% ee
Scheme 4.
(Table 2, entries 1, 3, 9, and 11). At the same time, PR-
configured analogues 9b,c gave alkylated ketones with pro-
nounced moderate enantioselectivity in the range of 21–
50% ee. Clearly, an R configuration of the P-stereogenic
Conclusion
center leads to enhanced enantioselectivity of the conjugate
New P-stereogenic phosphoramidites were synthesized
addition. It has been shown above that, due to steric fac- and investigated by NMR spectroscopic methods and sin-
tors, the PS- and PR-configured BH3–phosphoramidite gle-crystal X-ray structural analysis. PS and PR dia-
complexes 6b and 7d have slightly different molecular struc- stereomers can be simply separated by column chromatog-
tures (Figure 1 and Figure 2). The structural difference raphy and distinguished by using NMR spectroscopy. It ap-
could be an important factor, thereby distinguishing the peared that the configuration of the P-stereogenic center in
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P-Stereogenic Pinene-Derived Phosphoramidites
and then at room temperature for 24 h. After filtration, all volatiles
were removed in vacuo. The residue was mixed at 0 °C with
BH3·THF complex (1 m solution in THF, 3.00 mL, 3.00 mmol) and
stirred at 0 °C for 2 h. After evaporation under reduced pressure,
the stereoisomeric products (ratio of stereoisomers was always 1:1
according to GC) were separated and purified by means of flash
chromatography on silica gel.
a free ligand, generated from its BH3 complex, is rather
stable even at elevated temperatures, though this could be
dependent on the amine functionality. Preliminary experi-
ments showed that the configuration of the P-chiral center
in a phosphoramidite ligand has a distinct influence on the
enantioselectivity of a conjugate addition reaction. The PS
ligand favors the formation of an R-alkylated product, and
vice versa for the PR ligand. In addition, PS- and PR-config-
ured (–)-pinane-based phosphoramidites displayed slight
structural differences in the conformation of a phos-
phoramidite cycle. Such structural divergence between PS
and PR isomers could be the reason that enantioselectivity
in conjugated addition of Et2Zn to cyclohexenone and oc-
tenone was low when PS-configured phosphoramidite li-
gands were employed. At the same time, PR-phosphoramid-
ites showed enhanced enantioselectivity up to 50% ee. Fur-
ther studies to improve overall enantioselectivity of conju-
gate addition reactions are currently in progress.
(1R,2S,4R,6S,8R)-N,N-Dimethyl(4-boronato-2,9,9-trimethyl-3,5-di-
oxa-4-phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (6a) and (1R,2R,
4R,6S,8R)-N,N-Dimethyl(4-boronato-2,9,9-trimethyl-3,5-dioxa-4-
phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (7a): According to the ge-
neral procedure, treatment of 5a (1.17 g, 8.00 mmol) with cis-pinan-
diol
2 (1.36 g, 8.00 mmol), Et3N (2.24 mL, 16 mmol), and
BH3·THF complex (1 m solution in THF, 8.00 mL, 8.00 mmol) in
THF (20 mL) gave after flash chromatography separation [eluent:
EtOAc/PE, 1:10, silica gel; Rf (6a) = 0.28, Rf (7a) = 0.38] complexes
6a (766 mg, 37%) and 7a (504 mg, 25%).
Complex 6a: M.p. 90 °C. C12H25BNO2P (257.12): calcd. C 56.06,
H 9.80, N 5.45; found C 56.74, H 9.90, N 5.49. 1H NMR
1
(250 MHz, CDCl3, 298 K): δ = 0.69 (1:1:1:1 br. qd, JB,H = 92 Hz,
2JPH, = 15 Hz, 3 H, BH3), 0.87 (s, 3 H, 12-H), 1.30, 1.57 (each s,
2
each 3 H, 11 and 11Ј-H), 1.88 (d, JH,H = 11.0 Hz, 10-Hax), 1.94
Experimental Section
3
(m, 1 H, 8-H), 2.12 (m, 1 H, 7-Hax), 2.17 (t, JH,H = 5.7 Hz, 1 H,
2
3
3
1-H), 2.25 (dtd, JH,H = 11.0 Hz, JH,H = 5.7 Hz, JH,H = 2.2 Hz,
General Information: All reactions were carried out under a nitro-
gen atmosphere with Schlenk-type glassware. Solvents were dried
and distilled under nitrogen prior to use. Reaction progress and
purity were monitored by GC with a Hewlett–Packard HP 6890
equipped with a HP-5MS column (30 mϫ0.32 mm) or with a
Thermo-Finnigan Trace GC Ultra equipped with a Optima-5MS
column (30 mϫ0.25 mm) using different temperature programs.
Hydrogen was used as a carrier gas. Enantioselectivities were deter-
mined by GC on chiral stationary phases with a Fisons HRGC
MEGA 8560 or a Thermo-Finnigan Trace GC Ultra instrument.
The enantiomers are stated as major and minor with their exact
retention times. Flash chromatography was performed on silica gel,
grain size 40–63 μm (Macherey–Nagel).
1 H, 10-Heq), 2.41 (AB type ddt, JH,H = 14.9 Hz, JH,H-trans
=
2
3
8.8 Hz, JH,H = 2.5 Hz, 1 H, 7-Heq), 2.76 (d, JP,H = 9.8 Hz, 6 H,
3
3
3
3
3
NMe2), 4.59 (ddd, JP,H = 9.3 Hz, JH,H-trans = 8.8 Hz, JH,H-cis
=
2.8 Hz, 1 H, 6-H) ppm. 13C{1H} NMR (63 MHz, CDCl3, 298 K):
δ = 24.3 (C-12), 26.3 (C-10), 27.1, 28.4 (C-11 and C-11Ј), 35.0 (d,
3JP,C = 3.8 Hz, C-7), 36.2 (2JP,C = 5.3 Hz, NMe2), 38.8 (C-9), 39.3
3
2
(C-8), 52.2 (d, JP,C = 5.5 Hz, C-1), 79.5 (d, JP,C = 4.8 Hz, C-6),
88.9 (d, 2JP,C = 7.2 Hz, C-2) ppm. 31P{1H} NMR (162 MHz, C6D6,
298 K) δ = 144.9 ppm. IR (film): ν = 3312, 2978, 2938 (s), 2873,
˜
2821, 2391 (br), 2362 (br), 2270, 2135, 1481, 1450, 1388, 1379,
1355, 1302, 1265, 1245, 1190, 1138, 1124, 1075, 1056, 1026 (s), 1008
(s), 940, 921, 897, 872, 855, 837, 808, 765, 739, 705, 648 cm–1. MS
(EI): m/z (%) = 257 (1) [M+], 244 (6), 243 (60), 228 (1), 214 (1),
200 (3), 152 (2), 137 (3), 136 (16), 135 (23), 119 (16), 108 (29), 94
(10), 93 (100), 80 (7), 77 (14), 55 (10), 44 (17), 41 (23), 29 (7).
[α]2D0 = +15.6 (c = 1, CH2Cl2).
The following instruments were used for physical characterization
of the compounds. Elemental analyses: Carlo–Erba Strumenta-
zione Elemental Analyzer, Modell 1106. NMR spectroscopy:
Bruker AC 250 F (1H, 250 MHz; 13C, 63 MHz), Bruker ARX-500
(1H, 500 MHz; 13C, 126 MHz), Bruker ARX-300 (31P, 121 MHz).
Assignments of the resonances are supported by 2D experiments
and chemical-shift calculations. 1H and 13C NMR spectra were ref-
erenced to an internal Me4Si standard, 31P NMR spectra were ref-
erenced to an external P(OEt)3 sample in C6D6 (31P: δ =
138.0 ppm). IR: Bruker 22 FTIR Spectrometer with an golden-gate
single-reflection Diamant ATR system. MS: Finnigan MAT 95
Spectrometer (CI) with methane as a carrier gas, Varian MAT711
(EI, 70 eV). Optical rotation: Perkin–Elmer 241LC Polarimeter
(20 °C, 589 nm).
Complex 7a: M.p. 92 °C. C12H25BNO2P (257.12): calcd. C 56.06,
H 9.80, N 5.45; found C 56.20, H 9.69, N 5.41. 1H NMR
1
(250 MHz, CDCl3, 298 K): δ = 0.66 (1:1:1:1 br. qd, JB,H = 92 Hz,
2JP,H = 15 Hz, 3 H, BH3), 0.88 (s, 3 H, 12-H), 1.32, 1.65 (each s,
each 3 H, 11 and 11Ј-H), 1.67 (d, 2JH,H = 10.4 Hz, 10-Hax, tentative
2
assignment), 1.98 (m, 1 H, 8-H), 2.03 (dm, JH,H = 14.1 Hz, 1 H,
3
2
7-Hax), 2.18 (t, JH,H = 5.4 Hz, 1 H, 1-H), 2.24 (dtd, JH,H
=
10.4 Hz, JH,H = 5.4 Hz, JH,H = 2.2 Hz, 1 H, 10-Heq), 2.45 (dm,
3
3
2JH,H = 14.1 Hz, 1 H, 7-Heq), 2.82 (d, 3JP,H = 9.8 Hz, 6 H, NMe2),
3
3
3
4.49 (ddd, JP,H = 9.0 Hz, JH,H-trans = 8.7 Hz, JH,H-cis = 2.5 Hz, 1
H, 6-H) ppm. 13C{1H} NMR (63 MHz, CDCl3, 298 K): δ = 24.4
X-ray Diffraction: Data sets were collected with a Nicolet P3F dif-
fractometer. Programs used for data collection: Siemens P3/PC
Data Collection System; for data reduction: SHELXTL-plus,
XDISK; structure solution: SHELXS-97; for structure refinement:
SHELXS-97; graphics: SHELXTL-plus, XP.[14]
3
(C-12), 25.6 (C-10), 27.1, 28.5 (C-11 and C-11Ј), 34.3 (d, JP,C
=
3.0 Hz, C-7), 36.4 (2JP,C = 6.4 Hz, NMe2), 39.1 (C-9), 40.0 (C-8),
52.1 (d, JP,C = 4.3 Hz, C-1), 76.7 (C-6), 86.2 (C-2) ppm. 31P{1H}
3
NMR (162 MHz, C D , 298 K): δ = 142.1 ppm. IR (film): ν =
˜
6
6
3017, 2984, 2943, 2922, 2852, 2852, 2822, 2799, 2382 (s), 2351,
1737, 1476, 1452, 1387, 1370, 1353, 1307, 1279, 1266, 1248, 1229,
1186, 1159, 1134, 1117, 1076, 1065, 1013, 998, 983, 953, 931, 914,
890, 869, 849 cm–1. MS (EI): m/z (%) = 258 (1) [M+], 245 (1), 244
(2), 243 (67), 228 (2), 214 (1), 200 (4), 173 (3), 137 (3), 136 (17),
135 (25), 121 (10), 108 (18), 95 (3), 94 (10), 93 (100), 80 (6), 77
(11), 55 (8), 45 (8), 44 (14), 41 (17), 29 (5), 28 (17). [α]2D0 = –60.5 (c
= 1, CHCl3).
General Procedure for Preparation of Complexes 6a–d and 7a–d:
Et3N (607 mg, 6.00 mmol) was added at room temperature to a
stirred solution of cis-pinandiol 2 (510 mg, 3.00 mmol) in THF
(10 mL). The reaction was stirred at room temperature for 15 min
and then cooled to 0 °C. N,N-Dialkylaminophosphorus dichlorides
5a–d (3.00 mmol) was added dropwise to this cooled mixture at
0 °C, and the resulting suspension was stirred at 0 °C for 45 min
Eur. J. Inorg. Chem. 2011, 384–392
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
389

D. Hobuß, A. Baro, K. V. Axenov, S. Laschat, W. Frey
FULL PAPER
(1R,2R,4S,6S,8R)-N,N-Diethyl(4-boronato-2,9,9-trimethyl-3,5-dioxa-
4-phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (6b) and (1R,2R,
4R,6S,8R)-N,N-Diethyl(4-boronato-2,9,9-trimethyl-3,5-dioxa-4-
phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (7b): According to the ge-
neral procedure, treatment of 5b (522 mg, 3.00 mmol) with cis-pin-
andiol 2 (510 mg, 3.00 mmol) gave after flash chromatography sep-
aration [eluent: EtOAc/PE, 1:10, silica gel; Rf (6b) = 0.29, Rf (7b)
= 0.42] complexes 6b (167 mg, 20%) and 7b (205 mg, 24%).
parameters, 28 restraints (disorder of one ethyl function of the di-
ethylamino moiety); R1 = 0.0643, wR2 = 0.1641 {[IՆ2σ(I)]}; max.
(min.) residual electron density 0.270 (–0.225) eÅ–3; Flack param-
eter 0.0(2), data collection with a Nicolet P3F diffractometer.
(1R,2R,4S,6S,8R)-N,N-Diisopropyl-(4-boronato-2,9,9-trimethyl-3,5-
dioxa-4-phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (6c) and (1R,2R,
4R,6S,8R)-N,N-Diisopropyl-(4-boronato-2,9,9-trimethyl-3,5-dioxa-
4-phosphatricyclo[6.1.1.02,6]dec-4-yl)amine (7c): According to the
general procedure, treatment of 5c (1.61 g, 8.00 mmol) with cis-
pinandiol 2 (1.36 g, 8.00 mmol), Et3N (2.24 mL, 16 mmol), and
BH3·THF complex (1 m solution in THF, 8.00 mL, 8.00 mmol) in
Complex 6b: M.p. 85 °C. C14H29BNO2P (285.17): calcd. C 58.97,
H 10.25, N 4.91; found C 59.29, H 10.15, N 4.57. 1H NMR
1
(250 MHz, CDCl3, 298 K): δ = 0.69 (1:1:1:1 br. q, JB,H = 90 Hz,
3 H, BH3), 0.87 (s, 3 H, 12-H), 1.12 (t, 3JH,H = 7.0 Hz, 6 H, CH3Et), THF (20 mL) gave after flash chromatography separation [eluent:
1.30, 1.56 (each s, each 3 H, 11 and 11Ј-H), 1.94 (m, 1 H, 8-H),
EtOAc/PE, 1:10, silica gel; Rf (6c) = 0.31, Rf (7c) = 0.47] complexes
6c (851 mg, 34%) and 7c (778 mg, 31%).
2
1.98 (d, JH,H = 10.8 Hz, 10-Hax), 2.13 (m, 1 H, 7-Hax), 2.17 (t,
2
3
3JH,H = 5.5 Hz, 1 H, 1-H), 2.24 (dtd, JH,H = 10.8 Hz, JH,H
=
=
Complex 6c: M.p. 130–131 °C. C16H33BNO2P (313.23): calcd. C
5.5 Hz, JH,H = 2.2 Hz, 1 H, 10-Heq), 2.41 (AB type ddt, JH,H
3
2
1
61.35, H 10.62, N 4.47; found C 61.47, H 10.51, N 4.47. H NMR
14.9 Hz, JH,H-trans = 8.9 Hz, JH,H = 2.4 Hz, 1 H, 7-Heq), 3.15 (m,
3
3
1
(250 MHz, CDCl3, 298 K): δ = 0.83 (1:1:1:1 br. q, JB,H = 87 Hz,
3
3
3
4 H, CH2Et), 4.58 (ddd, JP,H = 9.7 Hz, JH,H-trans = 8.9 Hz, JH,H-
3
3 H, BH3), 0.87 (s, 3 H, 12-H), 1.29, 1.32 [each d, JH,H = 7.0 Hz,
= 2.8 Hz, 1 H, 6-H) ppm. 13C{1H} NMR (63 MHz, CDCl3,
cis
each 6 H, CH3iPr(A) and CH3iPr(B)], 1.30, 1.57 (each s, each 3 H, 11
298 K): δ = 14.1 (d, JP,C = 2.0 Hz, CH3Et), 24.4 (C-12), 26.3 (C-
3
2
and 11Ј-H), 1.93 (m, 1 H, 8-H), 2.02 (d, JH,H = 10.5 Hz, 10-Hax),
10), 27.1, 28.4 (C-11 and C-11Ј), 35.0 (d, 3JP,C = 3.7 Hz, C-7), 38.7
3
2.16 (m, 1 H, 7-Hax), 2.17 (t, JH,H = 5.3 Hz, 1 H, 1-H), 2.22 (m,
(d, JP,C = 5.6 Hz, CH2Et), 38.8 (C-9), 39.4 (C-8), 52.2 (d, JP,C
=
2
3
2
3
1 H, 10-Heq), 2.42 (AB type ddt, JH,H = 14.8 Hz, JH,H-trans
=
=
2
2
5.6 Hz, C-1), 79.2 (d, JP,C = 4.5 Hz, C-6), 89.0 (d, JP,C = 7.2 Hz,
8.8 Hz, JH,H = 2.4 Hz, 1 H, 7-Heq), 3.71 (d of septet, JP,H
3
3
C-2) ppm. 31P{1H} NMR (162 MHz, C6D6, 298 K) δ = 144.8 ppm.
15.1 Hz, JH,H = 7.0 Hz, 2 H, CHiPr), 4.60 (ddd, JP,H = 9.3 Hz,
3
3
IR (film): ν = 2976, 2931, 2874, 2387, 2255, 2145, 1741, 1466, 1449,
˜
3JH,H-trans = 8.8 Hz, JH,H-cis = 2.7 Hz, 1 H, 6-H) ppm. 13C{1H}
3
1382, 1264, 1210, 1173, 1134, 1077, 1027, 1007, 990, 953, 338, 898,
870, 806, 789, 693, 643 cm–1. MS (EI): m/z (%) = 285 (3) [M+], 272
(8), 271 (69) [M+ – BH3], 256 (7), 242 (1), 228 (2), 199 (3), 165 (3),
164 (40), 148 (2), 138 (9), 135 (23), 120 (23), 94 (13), 93 (100), 79
(8), 72 (24), 58 (8), 44 (3), 43 (12), 28 (19). [α]2D0 = Ϯ 0 (c = 1,
CHCl3).
3
NMR (63 MHz, CDCl3, 298 K): δ = 22.7, 23.5 [two d, JP,C = 2.0/
2.3 Hz, CH3iPr(A) and CH3iPr(B)], 24.4 (C-12), 26.1 (C-10), 27.1, 28.6
(C-11 and C-11Ј), 35.0 (d, 3JP,C = 4.0 Hz, C-7), 38.8 (C-9), 39.5 (C-
8), 46.1 (d, JP,C = 6.2 Hz, CHiPr), 52.5 (d, JP,C = 5.9 Hz, C-1),
2
3
2
2
79.5 (d, JP,C = 5.3 Hz, C-6), 89.6 (d, JP,C = 7.7 Hz, C-2) ppm.
31P{1H} NMR (121 MHz, C6D6, 298 K): δ = 145.1 ppm. IR (film):
Complex 7b: M.p. 51 °C. C14H29BNO2P (285.17): calcd. C 58.97,
ν = 2976, 2933 (s), 2875, 2397 (s), 2269, 2160, 1634, 1474, 1449,
˜
H 10.25, N 4.91; found C 59.08, H 10.14, N 4.85. 1H NMR
1411, 1387, 1369, 1313, 1282, 1264, 1243, 1205, 1182, 1157, 1122,
1
(250 MHz, CDCl3, 298 K): δ = 0.66 (1:1:1:1 br. q, JB,H = 88 Hz,
1077, 1057, 1010, 985 (s), 838, 918, 894, 871, 852 cm–1. MS (EI):
3 H, BH3), 0.88 (s, 3 H, 12-H), 1.13 (t, 3JH,H = 7.1 Hz, 6 H, CH3Et), m/z (%) = 313 (3) [M+], 300 (13), 299 (70) [M+ – BH3], 284 (16),
2
1.32, 1.66 (each s, each 3 H, 11 and 11Ј-H), 1.58 (d, JH,H
=
257 (3), 256 (15), 217 (1), 200 (1), 199 (4), 192 (10), 176 (1), 166
10.3 Hz, 10-Hax), 1.98 (m, 1 H, 8-H), 2.02 (dm, JH,H = 14.0 Hz, 1 (5), 150 (10), 136 (23), 135 (35), 94 (6), 93 (100), 79 (6), 55 (7), 43
2
3
2
H, 7-Hax), 2.18 (t, JH,H = 5.6 Hz, 1 H, 1-H), 2.25 (dtd, JH,H
=
(23), 27 (5). [α]2D0 = +6.5 (c = 1, CH2Cl2). Ligand 6c was deprotected
10.3 Hz, JH,H = 5.6 Hz, JH,H = 1.8 Hz, 1 H, 10-Heq), 2.43 (dm, by heating at 65 °C for 12 h with an excess amount of Et2NH.
2JH,H = 14.0 Hz, 1 H, 7-Heq), 3.25 (m, 4 H, CH2Et), 4.47 (ddd, 3JP,H 31P{1H} NMR spectrum of free ligand 8c (121 MHz, C6D6, 298 K):
= 9.0 Hz, JH,H-trans = 6.7 Hz, JH,H-cis = 2.4 Hz, 1 H, 6-H) ppm. δ = 151.8 ppm. The free ligand was treated with BH3·THF complex
3
3
3
3
3
13C{1H} NMR (63 MHz, CDCl3, 298 K): δ = 14.4 (d, JP,C
=
at 0 °C for 2 h to give back complex 6c [31P(1H) NMR (121 MHz,
1.6 Hz, CH3Et), 24.3 (C-12), 25.5 (C-10), 27.1, 28.5 (C-11 and C- C6D6, 298 K): δ = 145.1 ppm].
11Ј), 34.4 (d, JP,C = 3.5 Hz, C-7), 39.0 (d, JP,C = 6.3 Hz, CH2Et),
3
2
Complex 7c: M.p. 82 °C. C16H33BNO2P (313.23): calcd. C 61.35,
39.1 (C-9), 39.8 (C-8), 52.0 (d, 3JP,C = 4.4 Hz, C-1), 76.4 (C-6), 85.7
H 10.62, N 4.47; found C 61.10, H 10.56, N 4.19. 1H NMR
(C-2) ppm. 31P{1H} NMR (162 MHz, C6D6, 298 K):
δ =
1
(250 MHz, CDCl3, 298 K): δ = 0.77 (1:1:1:1 br. q, JB,H = 87 Hz,
142.8 ppm. IR (film): ν = 2980, 2936 (s), 2871, 2382 (s), 2351, 2247,
˜
3
3 H, BH3), 0.88 (s, 3 H, 12-H), 1.31, 1.32 [each d, JH,H = 7.0 Hz,
2117, 2009, 1722, 1453, 1382, 1292, 1248, 1208, 1173, 1130, 1078,
1029, 1008, 989, 960, 936, 915, 889, 870, 837, 800, 790, 733, 691,
631 cm–1. MS (EI): m/z (%) = 285 (1) [M+], 273 (1), 272 (12), 271
(72) [M+ – BH3], 256 (9), 242 (1), 228 (3), 199 (3), 165 (1), 164 (8),
148 (1), 138 (15), 135 (26), 120 (22), 94 (10), 93 (100), 79 (7), 72
(25), 58 (9), 44 (3), 43 (12), 29 (3), 28 (14). [α]2D0 = –49.4 (c = 1,
CHCl3).
each 6 H, CH3iPr(A) and CH3iPr(B)], 1.31, 1.70 (each s, each 3 H, 11
2
and 11Ј-H), 1.59 (d, JH,H = 10.2 Hz, 10-Hax), 1.96 (m, 1 H, 8-H),
2.01 (dm, 2JH,H = 14.6 Hz, 1 H, 7-Hax), 2.18 (t, 3JH,H = 5.4 Hz, 1 H,
1-H), 2.21 (dtd, 2JH,H = 10.2 Hz, 3JH,H = 5.4 Hz, 3JH,H = 2.2 Hz, 1
2
3
H, 10-Heq), 2.43 (AB type ddm, JH,H = 14.6 Hz, JH,H-trans
=
=
8.8 Hz, 1 H, 7-Heq), 3.97 (d of septet, JP,H = 15.5 Hz, JH,H
3
3
7.0 Hz, 2 H, CHiPr), 4.50 (ddd, JH,H-trans = 8.8 Hz, JP,H = 6.0,
3
3
X-ray Crystal Structure Analysis of Complex 6b: Formula
C14H29BNO2P; colorless crystal 0.9ϫ0.6ϫ0.5 mm; Mr = 285.16;
3JH,H-cis = 2.1 Hz, 1 H, 6-H) ppm. 13C{1H} NMR (63 MHz,
3
iPr(A)
CDCl3, 298 K): δ = 23.1, 23.2 [two d, JP,C = 2.1/2.6 Hz, CH3
a
=
7.548(3) Å,
b
=
10.880(4) Å,
c
=
21.343 (7) Å;
V
=
and CH3iPr(B)], 24.4 (C-12), 25.3 (C-10), 27.1, 28.8 (C-11 and C-
1752.8(11) Å3; ρcalcd. = 1.081 gcm–3; μ = 0.1550 mm–1; Z = 4; or-
thorhombic, space group P212121 (no. 19); λ = 0.71073 Å; T =
293(2) K; Wyckoff scan, 3140 reflections collected (–1ՅhՅ9,
–1ՅkՅ14, –1ՅlՅ28), [(sinθ)/λ] = 0.66 Å–1; 2966 independent
(Rint = 0.0605) and 1886 observed reflections [IՆ2σ(I)]; 192 refined
11Ј), 34.2 (d, JP,C = 3.6 Hz, C-7), 39.2 (C-9), 39.8 (C-8), 46.2 (d,
3
2JP,C = 6.1 Hz, CHiPr), 52.3 (d, JP,C = 3.9 Hz, C-1), 76.1 (C-6),
3
85.7 (C-2) ppm. 31P{1H} NMR (162 MHz, C6D6, 298 K): δ =
143.2 ppm. IR (neat): ν = 3580, 2985, 2915, 2874, 2397 (s), 2354,
˜
2276, 2177, 2148, 2018, 1967, 1648, 1472, 1451, 1409, 1387, 1370,
390
www.eurjic.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2011, 384–392

P-Stereogenic Pinene-Derived Phosphoramidites
1280, 1244, 1205, 1157, 1127, 1078, 1058, 1014, 984, 951, 935, 913, a = 7.9654(16) Å, b = 10.539(2) Å, c = 10.4857(15) Å; β =
890, 869 cm–1. MS (EI): m/z (%) = 301 (1), 300 (11), 299 (60) [M+
–
101.312(13)°; V = = μ =
863.2(3) Å3; ρcalcd. 1.143 gcm–3;
BH3], 284 (11), 257 (3), 256 (17), 217 (1), 199 (3), 166 (7), 150 (13),
0.160 mm–1; Z = 2; monoclinic, space group P21 (no. 4); λ =
0.71073 Å; T = 293(2) K; Wyckoff-Scan, 4171 reflections collected
(0ՅhՅ12, 0Յ kՅ17, –16ՅlՅ16), [(sinθ)/λ] = 0.81 Å–1; 3951 in-
dependent (Rint = 0.0320) and 2941 observed reflections [IՆ2σ(I)],
194 refined parameters; R1 = 0.0672, wR2 = 0.1620 ([IՆ2σ(I)]);
max. (min.) residual electron density 0.342 (–0.218) eÅ–3; Flack
parameter –0.07(16), data collection with a Nicolet P3F dif-
fractometer.
136 (27), 135 (30), 94 (13), 93 (100), 44 (8), 43 (25), 27 (5). [α]D20
–43.9 (c = 1, CH2Cl2).
=
(1R,2R,4S,6S,8R)-1-(4-Boronato-2,9,9-trimethyl-3,5-dioxa-4-phos-
phatricyclo[6.1.1.02,6]dec-4-yl)piperidine (6d) and (1R,2R,
4R,6S,8R)-1-(4-Boronato-2,9,9-trimethyl-3,5-dioxa-4-phosphatricyclo-
[6.1.1.02,6]dec-4-yl)piperidine (7d): According to the general pro-
cedure, treatment of 5d (1.49 g, 8.00 mmol) with cis-pinandiol 2
(1.36 g, 8.00 mmol), Et3N (2.24 mL, 16 mmol), and BH3·THF
complex (1 m solution in THF, 8.00 mL, 8.00 mmol) in THF
(30 mL) gave after flash chromatography separation [eluent:
EtOAc/PE, 1:10, silica gel; Rf (6d) = 0.40, Rf (7d) = 0.47] complexes
6d (691 mg, 29%) and 7d (911 mg, 38%).
General Procedure for Enantioselective 1,4-Conjugate Addition of
Et2Zn to α,β-Unsaturated Substrates with Phosphoramidite Pinane-
Based Complexes 6a–d and 7a–d: Prior to the addition reaction,
complexes 6a–d and 7b–d were deprotected by heating in Et2NH
(3 mL) at 65 °C for 12 h. After removal of all volatiles and drying
for 2 h under vacuum, the residue (the deprotected ligand) was dis-
solved in toluene, and the aliquot of this stock solution (1 mL,
0.10 mmol of ligand) was added to a suspension of CuI thiophene-
carboxylate (9.5 mg, 0.05 mmol) in toluene (2 mL). Subsequently,
Et2Zn (1 m solution in hexane, 1.5 mL, 1.5 mmol) and then sub-
strate (1.00 mmol) were added at –20 °C. The resulting mixture was
stirred at –20 °C for 3 h. The reaction was quenched with HCl (1 n,
20 mL). After extraction with Et2O (3ϫ15 mL), the combined or-
ganic phases were washed with water (5 mL) and dried with
MgSO4. Solvents were evaporated under reduced pressure, and the
residue was directly investigated by GC or HPLC on chiral phase
to determine the enantiomeric selectivity of the addition reaction.
(For the results of enantioselective addition, see Table 2 and the
Supporting Information).
Complex 6d: M.p. 69–70 °C. C15H29BNO2P (297.19): calcd. C
60.62, H 9.84, N 4.71; found C 60.77, H 9.82, N 4.60. 1H NMR
1
(250 MHz, CDCl3, 298 K): δ = 0.68 (1:1:1:1 br. q, JB,H = 90 Hz,
3 H, BH3), 0.87 (s, 3 H, 12-H), 1.30, 1.55 (each s, each 3 H, 11 and
2
11Ј-H), 1.52 (m, 2 H, 15-H), 1.59 (m, 4 H, 14-H), 1.90 (d, JH,H
=
10.9 Hz, 10-Hax), 1.93 (m, 1 H, 8-H), 2.12 (m, 1 H, 7-Hax), 2.16 (t,
2
3
3JH,H = 5.6 Hz, 1 H, 1-H), 2.23 (dtd, JH,H = 10.9 Hz, JH,H
=
=
5.6 Hz, JH,H = 2.2 Hz, 1 H, 10-Heq), 2.41 (AB type ddt, JH,H
3
2
14.7 Hz, JH,H-trans = 9.1 Hz, JH,H = 2.4 Hz, 1 H, 7-Heq), 3.16 (m,
3
3
4 H, 13-H), 4.58 (ddd, 3JP,H = 9.5 Hz, JH,H-trans = 9.1 Hz, JH,H-cis
3
3
= 2.8 Hz, 1 H, 6-H) ppm. 13C{1H} NMR (63 MHz, CDCl3,
3
298 K): δ = 24.3, 24.4 (C-12 and C-15), 26.3 (C-10), 26.3 (d, JP,C
= 2.9 Hz, C-14), 27.1, 28.4 (C-11 and C-11Ј), 35.1 (d, JP,C
2.9 Hz, C-7), 38.7 (C-9), 39.4 (C-8), 45.1 (d, JP,C = 3.8 Hz, C-13),
3
=
2
3
2
Supporting Information (see also the footnote on the first page of
this article): Text, tables, and figures that give further experimental
and spectroscopic details.
52.3 (d, JP,C = 5.4 Hz, C-1), 79.3 (d, JP,C = 4.6 Hz, C-6), 88.8 (d,
2JP,C = 7.5 Hz, C-2) ppm. 31P{1H} NMR (162 MHz, C6D6, 298 K)
δ = 146.0 ppm. IR (neat): ν = 3160, 2967, 2924 (s), 2866, 2849, 295
˜
(s), 2359, 2187, 1964, 1468, 1443, 1389, 1373, 1360, 1338, 1277,
1259, 1208, 1169, 1139, 1112, 1057, 1025, 1012, 992, 954, 918, 898,
870, 853 cm–1. MS (EI): m/z (%) = 298 (1), 297 (5) [M+], 284 (12),
283 (67) [M+ – BH3], 268 (1), 240 (2), 199 (3), 177 (3), 176 (25),
152 (2), 149 (9), 132 (23), 108 (25), 94 (10), 93 (100), 56 (3), 55
(13), 41 (18), 29 (5), 28 (18). [α]2D0 = +1.2 (c = 1, CHCl3).
Acknowledgments
Generous financial support by the Deutsche Forschungsgemein-
schaft (DFG), the Fonds der Chemischen Industrie, and the Minis-
terium für Wissenschaft, Forschung und Kunst der Landes Baden-
Württemberg is gratefully acknowledged.
Complex 7d: M.p. 112 °C. C15H29BNO2P (297.19): calcd. C 60.62,
H 9.84, N 4.71; found C 60.82, H 9.94, N 4.67. 1H NMR
1
(250 MHz, CDCl3, 298 K): δ = 0.67 (1:1:1:1 br. q, JB,H = 90 Hz,
[1] a) B. L. Feringa, R. Naasz, R. Imbos, L. A. Arnold, in: Mod-
ern Organocopper Chemistry (Ed.: N. Krause), Wiley-VCH,
Weinheim, 2002, pp. 224–258; b) A. Alexakis, C. Benhaim, Eur.
J. Org. Chem. 2002, 3221–3236; c) A. Alexakis, in: ACS Sympo-
sium Series, 880 (Methodologies in Asymmetric Catalysis)
2004, p. 43–59; for reviews, see: d) D. A. Evans, T. Rovis, J. S.
Johnson, Pure Appl. Chem. 1999, 71, 1407–1415; e) M. P. Sibi,
S. Manyem, Tetrahedron 2000, 56, 8033–8061; f) N. Krause,
A. Hoffmann-Röder, Synthesis 2001, 171–196; g) O. Molt, T.
Schrader, Synthesis 2002, 2633–2670; h) S. Woodward, Angew.
Chem. 2005, 117, 5696–5698; Angew. Chem. Int. Ed. 2005, 44,
5560–5562; i) J. Christoffers, G. Koripelly, A. Rosiak, M.
Rössle, Synthesis 2007, 1279–1300; j) A. Alexakis, J. E.
Bäckvall, N. Krause, O. Pàmies, M. Diéguez, Chem. Rev. 2008,
108, 2796–2823; k) S. R. Harutyunyan, T. den Hartog, K. Ge-
urts, A. J. Minnaard, B. L. Feringa, Chem. Rev. 2008, 108,
2824–2852; l) T. Jerphagnon, M. G. Pizzuti, A. J. Minnaard,
B. L. Feringa, Chem. Soc. Rev. 2009, 38, 1039–1075.
3 H, BH3), 0.88 (s, 3 H, 12-H), 1.32, 1.65 (each s, each 3 H, 11 and
2
11Ј-H), 1.53 (m, 2 H, 15-H), 1.59 (m, 4 H, 14-H), 1.60 (d, JH,H
=
2
10.5 Hz, 10-Hax), 1.98 (m, 1 H, 8-H), 2.02 (dm, JH,H = 13.9 Hz, 1
3
2
H, 7-Hax), 2.18 (t, JH,H = 5.5 Hz, 1 H, 1-H), 2.22 (dtd, JH,H
=
=
=
10.5, JH,H = 5.5, JH,H = 2.2 Hz, 1 H, 10-Heq), 2.44 (dm, JH,H
3
3
2
13.9 Hz, 1 H, 7-Heq), 3.28 (m, 4 H, 13-H), 4.48 (ddd, JP,H
3
3
3
9.2 Hz, JH,H-trans = 7.9 Hz, JH,H-cis = 2.3 Hz, 1 H, 6-H) ppm.
13C{1H} NMR (63 MHz, CDCl3, 298 K): δ = 24.3, 24.4 (C-12 and
3
C-15), 25.6 (C-10), 26.3 (d, JP,C = 2.9 Hz, C-14), 27.1, 28.5 (C-11
and C-11Ј), 34.4 (d, JP,C = 2.9 Hz, C-7), 39.1 (C-9), 40.0 (C-8),
45.3 (d, JP,C = 4.7 Hz, C-13), 52.2 (d, JP,C = 4.5 Hz, C-1), n.o.
3
2
3
(C-6), 86.1 (C-2) ppm. 31P{1H} NMR (162 MHz, C6D6, 298 K): δ
= 142.3 ppm. IR (neat): ν = 3522, 2986, 2939 (s), 2850, 2386 (s),
˜
1718, 1519, 1455, 1373, 1339, 1277, 1247, 1207, 1162, 1118, 1062,
1009, 992, 690, 914, 885, 867, 847, 801, 756, 731, 696, 635, 594,
561 cm–1. MS (EI): m/z (%) = 297 (1) [M+], 283 (84) [M+ – BH3],
268 (2), 240 (2), 213 (3), 201 (3), 176 (3), 161 (2), 150 (19), 136
(24), 132 (28), 119 (12), 108 (13), 93 (100), 84 (29), 77 (12), 67 (7),
55 (16), 41 (21), 39 (5). [α]2D0 = –29.3 (c = 1, CHCl3).
[2] For reviews on phosphoramidites, see: a) B. L. Feringa, Acc.
Chem. Res. 2000, 33, 346–353; b) A. H. M. de Vries, J. A. F.
Boogers, M. van den Berg, D. Pena, A. J. Minnaard, B. L. Fer-
inga, J. G. de Vries, Pharma Chem. 2003, 2, 33–36; c) M. T.
Reetz, Chim. Oggi 2003, 21, 5–8; d) M. van den Berg, D. Pena,
A. J. Minnaard, B. L. Feringa, L. Lefort, J. A. F. de Vries,
X-ray Crystal Structure Analysis of Complex 7d: Formula
C15H29BNO2P; colorless crystal 0.9ϫ0.7ϫ0.5 mm; Mr = 297.17;
Eur. J. Inorg. Chem. 2011, 384–392
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
391

D. Hobuß, A. Baro, K. V. Axenov, S. Laschat, W. Frey
FULL PAPER
H. M. Andre, J. G. de Vries, Chim. Oggi 2004, 22, 18–21; e) D.
Ager, J. G. de Vries, L. Lefort, A. H. M. de Vries, J. A. F. Boog-
ers, Pharma Chem. 2004, 3, 38–40; f) T. Jerphagnon, J.-L. Re-
naud, C. Bruneau, Tetrahedron: Asymmetry 2004, 15, 2101–
2111; g) S. P. Flanagan, P. J. Guiry, J. Organomet. Chem. 2006,
691, 2125–2154; h) C. Gennari, C. Monti, U. Piarulli, Pure
Appl. Chem. 2006, 78, 303–310; i) D. J. Ager, A. H. M. de Vries,
J. G. de Vries, Platinum Met. Rev. 2006, 50, 54–63; j) A. J. Min-
naard, B. L. Feringa, L. Lefort, J. G. de Vries, Acc. Chem. Res.
2007, 40, 1267–1277; k) L. Eberhardt, D. Armspach, J. Har-
rowfield, D. Matt, Chem. Soc. Rev. 2008, 37, 839–864; l) J. F.
Teichert, B. L. Feringa, Angew. Chem. 2010, 122, 2538–2582;
Angew. Chem. Int. Ed. 2010, 49, 2486–2528.
[9] a) D. Moulin, C. Darcel, S. Jugé, Tetrahedron: Asymmetry
1999, 10, 4729–4743; b) D. J. Brauer, K. W. Kottsieper, S. Roß-
enbach, O. Stelzer, Eur. J. Inorg. Chem. 2003, 1748–1755; c)
M. L. Christ, M. Zablocka, S. Spencer, R. J. Lavender, M. Le-
maire, J. P. Majoral, J. Mol. Catal. A 2006, 245, 210–216.
[10] D. Hobuß, C. Thöne, S. Laschat, A. Baro, Synthesis 2003,
2053–2056.
[11] For other terpene-derived P ligands, see: from camphor: a) B.
Bogdanovic´, B. Henc, B. Meister, H. Pauling, G. Wilke, Angew.
Chem. 1972, 84, 1102–1103; Angew. Chem. Int. Ed. Engl. 1972,
11, 1023–1024; b) J. D. Morrison, W. F. Masler, M. K. Neub-
erg, Adv. Catal. 1976, 25, 81–124; c) T. H. Johnson, D. K.
Pretzer, S. Thomen, V. J. K. Chaffin, G. Rangarajan, J. Org.
Chem. 1979, 44, 1878–1879; d) D. A. Knight, D. J. Cole-Hamil-
ton, D. C. Cupertino, J. Chem. Soc., Dalton Trans. 1990, 3051–
3054; e) E. U. Zhorov, K. N. Gavrilov, V. A. Pavlov, A. T. Tele-
shev, L. S. Gorshkova, E. E. Nifantev, E. I. Klabunovskii, Russ.
Chem. Bull. 1991, 871–876; f) I. V. Komarov, M. V. Gorichko,
M. Y. Kornilov, Tetrahedron: Asymmetry 1997, 8, 435–445; g)
A. Alexakis, J. Vastra, J. Burton, P. Mangeney, Tetrahedron:
Asymmetry 1997, 8, 3193–3196; h) T. Sell, S. Laschat, I. Dix,
P. G. Jones, Eur. J. Org. Chem. 2000, 4119–4124; i) X. Li, R.
Lou, C.-H. Yeung, A. S. C. Chan, W. K. Wong, Tetrahedron:
Asymmetry 2000, 11, 2077–2082; j) A. Monsees, S. Laschat,
Synlett 2002, 1011–1013; k) I. V. Komarov, A. Monsees, R. Ka-
dyrov, C. Fischer, U. Schmidt, A. Börner, Tetrahedron: Asym-
metry 2002, 13, 1615–1620; l) I. V. Komarov, A. Monsees, A.
Spannenberg, W. Baumann, U. Schmidt, C. Fischer, A. Börner,
Eur. J. Org. Chem. 2003, 138–150; from fenchone: m) B. Gold-
fuss, T. Löschmann, F. Rominger, Chem. Eur. J. 2004, 10, 5422–
5431; from pinene: n) F. Langer, P. Knochel, Tetrahedron Lett.
1995, 36, 4591–4594; o) A. Longeau, F. Langer, P. Knochel,
Tetrahedron Lett. 1996, 37, 2209–2212; p) E. J. Bergner, G.
Helmchen, Eur. J. Org. Chem. 2000, 419–423; q) K. W. Kotts-
ieper, U. Kühner, O. Stelzer, Tetrahedron: Asymmetry 2001, 12,
1159–1169; r) A. Gavryushin, K. Polborn, P. Knochel, Tetrahe-
dron: Asymmetry 2004, 15, 2279–2288.
[3] For recent examples of asymmetric conjugate additions using
phosphoramidites, see: a) C. Monti, C. Gennari, R. M. Steele,
U. Piarulli, Eur. J. Org. Chem. 2004, 3557–3565; b) T.
Pfretzschner, L. Kleemann, B. Janza, K. Harms, T. Schrader,
Chem. Eur. J. 2004, 10, 6048–6057; c) A. Duursma, J.-G.
Boiteau, L. Lefort, J. A. F. Boogers, A. H. M. de Vries, J. G.
de Vries, A. J. Minnaard, B. L. Feringa, J. Org. Chem. 2004, 69,
8045–8052; d) K. Li, A. Alexakis, Tetrahedron Lett. 2005, 46,
8019–8022; e) Y. Yamamoto, K. Kurihara, N. Sugishita, K.
Oshita, D. Piao, N. Miyaura, Chem. Lett. 2005, 34, 1224–1225;
f) T. Kop-Weiershausen, J. Lex, J.-M. Neudörfl, B. Goldfuss,
Beilstein J. Org. Chem. 2005, 1, DOI: 10.1186/1860-5397-1-6;
g) W. Zhang, C.-J. Wang, W. Gao, X. Zhang, Tetrahedron Lett.
2005, 46, 6087–6090; h) J. Esquivias, R. Gómez Arrayás, J. C.
Carretero, J. Org. Chem. 2005, 70, 7451–7454; i) A. Duursma,
D. Peña, A. J. Minnaard, B. L. Feringa, Tetrahedron: Asym-
metry 2005, 16, 1901–1904; j) A. Alexakis, V. Albrow, K. Bi-
swas, M. d’Augustin, O. Prieto, S. Woodward, Chem. Commun.
2005, 2843–2845; k) M. d’Augustin, L. Palais, A. Alexakis, An-
gew. Chem. 2005, 117, 1400–1402; Angew. Chem. Int. Ed. 2005,
44, 1376–1378; l) D. Polet, A. Alexakis, Tetrahedron Lett. 2005,
46, 1529–1532; m) N. Cramer, S. Laschat, A. Baro, Organome-
tallics 2006, 25, 2284–2291; n) E. Fillion, A. Wilsily, J. Am.
ˇ
Chem. Soc. 2006, 128, 2774–2775; o) R. Sebesta, M. G. Pizzuti,
A. J. Minnaard, B. L. Feringa, Adv. Synth. Catal. 2007, 349,
1931–1937; p) L. Palais, I. S. Mikhel, C. Bournaud, L. Mic-
ouin, C. A. Falciola, M. Vuagnoux-d’Augustin, S. Rosset, G.
Bernardinelli, A. Alexakis, Angew. Chem. 2007, 119, 7606–
7609; Angew. Chem. Int. Ed. 2007, 46, 7462–7465; q) J.-H. Xie,
Q.-L. Zhou, Acc. Chem. Res. 2008, 41, 581–593; r) B. Maciá,
M. Á. Fernández-Ibáñez, N. Mrsˇic´, A. J. Minnaard, B. L. Fer-
inga, Tetrahedron Lett. 2008, 49, 1877–1880; s) D.-Y. Zou, Z.-
C. Duan, X.-P. Hu, Z. Zheng, Tetrahedron: Asymmetry 2009,
[12] A. H. M. de Vries, A. Meetsma, B. L. Feringa, Angew. Chem.
1996, 108, 2526–2528; Angew. Chem. Int. Ed. Engl. 1996, 35,
2374–2376.
[13] A. van Rooy, D. Burger, P. C. J. Kamer, P. W. N. M. van Leeuwen,
Recl. Trav. Chim. Pays-Bas 1996, 115, 492–498.
[14] CCDC-785069 (7d) and -785070 (6b) contain the supplemen-
tary 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.
20, 235–239; t) M. Welker, S. Woodward, L. F. Veiros, M. J. [15] Similar difference in spectral features between PS and PR iso-
Calhorda, Chem. Eur. J. 2010, 16, 5620–5629.
[4] K. N. Gavrilov, V. N. Tsarev, A. A. Shiryaev, O. G. Bondarev,
S. E. Lyubimov, E. B. Benetsky, A. A. Korlyukov, M. Y. Anti-
pin, V. A. Davankov, H.-J. Gais, Eur. J. Inorg. Chem. 2004, 629–
634.
[5] M. T. Reetz, J.-A. Ma, R. Goddard, Angew. Chem. 2005, 117,
416–419; Angew. Chem. Int. Ed. 2005, 44, 412–415.
[6] Review: P.-H. Leung, Acc. Chem. Res. 2004, 37, 169–177.
[7] a) R. Ewalds, E. B. Eggeling, A. C. Hewat, P. C. J. Kamer,
P. W. N. M. van Leeuwen, D. Vogt, Chem. Eur. J. 2000, 6,
1496–1504; b) J. J. Carbó, A. Lledós, D. Vogt, C. Bo, Chem.
Eur. J. 2006, 12, 1457–1467.
mers has been already observed for chiral phosphoramidite li-
gands. See ref.[4]
[16] T. Imamoto, T. Oshiki, T. Onozawa, T. Kusumoto, K. Sato, J.
Am. Chem. Soc. 1990, 112, 5244–5252.
[17] a) B. L. Feringa, M. Pineschi, L. A. Arnold, R. Imbos,
A. H. M. de Vries, Angew. Chem. 1997, 109, 2733–2736; Angew.
Chem. Int. Ed. Engl. 1997, 36, 2620–2623; b) A. Alexakis, C.
Benhaim, S. Rosset, M. Humam, J. Am. Chem. Soc. 2002, 124,
5262–5263.
[18] a) A. Alexakis, S. Rosset, J. Allamand, S. March, F. Guillen,
C. Benhaim, Synlett 2001, 1375–1378; b) A. Alexakis, D. Polet,
S. Rosset, S. March, J. Org. Chem. 2004, 69, 5660–5667.
[19] A. Alexakis, J. Vastra, P. Mangeney, Tetrahedron Lett. 1997,
38, 7745–7748.
[8] a) T. Yamagishi, M. Ohnuki, T. Kiyooka, D. Masui, K. Sato,
M. Yamaguchi, Tetrahedron: Asymmetry 2003, 14, 3275–3279;
b) A. M. Taylor, R. A. Altman, S. L. Buchwald, J. Am. Chem.
Soc. 2009, 131, 9900–9901.
Received: September 6, 2010
Published Online: December 17, 2010
392
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Eur. J. Inorg. Chem. 2011, 384–392