A new class of modular P,N-ligand library for asymmetric Pd-catalyzed allylic substitution reactions: A study of the key Pd-π- allyl intermediates

DOI: 10.1002/chem.200901842

A New Class of Modular P,N-Ligand Library for Asymmetric Pd-Catalyzed

Allylic Substitution Reactions: A Study of the Key Pd–p-Allyl Intermediates

Javier Mazuela,^[a]Alexander Paptchikhine,^[b]Pꢀivi Tolstoy,^[b]Oscar Pꢁmies,^[a]

Montserrat Diꢂguez,*^[a]and Pher G. Andersson*^[b]

Abstract: A new class of modular P,N-

ligand library has been synthesized and

screened in the Pd-catalyzed allylic

substitution reactions of several sub-

strate types. These series of ligands can

be prepared efficiently from easily ac-

cessible hydroxyl–oxazole/thiazole de-

rivatives. Their modular nature enables

the bridge length, the substituents at

the heterocyclic ring and in the alkyl

backbone chain, the configuration of

the ligand backbone, and the substitu-

ents/configurations in the biaryl phos-

phite moiety to be easily and systemati-

cally varied. By carefully selecting the

ligand components, therefore, high

regio- and enantioselectivities (ee

values up to 96%) and good activities

are achieved in broad range of

a

mono-, di-, and trisubstituted linear

hindered and unhindered substrates

and cyclic substrates. The NMR spec-

troscopic and DFT studies on the Pd–

p-allyl intermediates provide a deeper

understanding of the effect of ligand

parameters on the origin of enantiose-

lectivity.

Keywords: allylic substitution

·

asymmetric catalysis · ligand design ·

N,P ligands · palladium

Introduction

bite angle of the ligand to create a chiral cavity in which the

allyl system is embedded. This idea opened up the successful

application of ligands with large bite angles for the allylic

substitution of sterically undemanding substrates.^[1,3]The

third strategy, developed by groups led by Helmchen, Pfaltz,

and Williams, was the use of heterodonor ligands that result

in an electronic discrimination of the two allylic terminal

carbon atoms due to the different trans influences of the

donor groups.^[1,4]This made it possible to successfully use a

wide range of heterodonor ligands (mainly P,N ligands) in

allylic substitution reactions.^[1]

Nowadays, many chiral ligands (mainly P and N ligands),

which possess either C₂or C₁symmetry, have been devel-

oped, and they provide high enantiomeric excesses for sev-

eral types of disubstituted substrates.^[1]Nevertheless, in gen-

eral, there is still a problem of substrate specificity (for ex-

ample, ee values are high in disubstituted linear hindered

substrates and low in unhindered substrates, and vice versa)

and reaction rates. Other types of substrates still require

much attention. For example, for monosubstituted sub-

strates, more active and more regio- and enantioselective Pd

catalysts are needed.^[1]Another challenging class of sub-

strates is that of trisubstituted substrates. Although a few

good enantioselective Pd-catalytic systems have been report-

ed, their activities are still very low.^[1]More research is

needed on the development of new ligands that can over-

come these limitations.

The development of methods for enantioselective carbon–

carbon and carbon–heteroatom bond formation is one of

the key issues in organic synthesis. A versatile method for

forming these bonds is palladium-catalyzed asymmetric al-

lylic substitution.^[1]

Most of the successful ligands reported to date for this

process have been designed using three main strategies. The

first one, developed by Hayashi and co-workers, was the use

of a secondary interaction of the nucleophile with a side

chain of the ligand to direct the approach of the nucleophile

to one of the allylic terminal carbon atoms.^[2]The second

one, developed by Trost and co-workers, was to increase the

[a] J. Mazuela, Dr. O. Pꢀmies, Dr. M. Diꢁguez

Departament de Quꢂmica Fꢂsica i Inorgꢀnica

Universitat Rovira i Virgili

C/Marcel lꢂDomingo, s/n. 43007 Tarragona (Spain)

Fax : (+34)977559563

E-mail: montserrat.dieguez@urv.cat

[b] A. Paptchikhine, P. Tolstoy, Prof. P. G. Andersson

Department of Biochemistry and Organic Chemistry

Uppsala University, BOX 576, 751 23 Uppsala (Sweden)

Fax : (+46)18-471-3818

E-mail: pher.andersson@kemi.uu.se

Supporting information for this article is available on the WWW

under http://dx.doi.org/10.1002/chem.200901842.

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Chem. Eur. J. 2010, 16, 620 – 638

FULL PAPER

In this context, we recently demonstrated that the pres-

ence of biaryl phosphite moieties in ligand design is highly

advantageous because 1) substrate specificity decreases be-

cause the chiral pocket created (i.e., the chiral cavity in

which the allyl is embedded) is flexible enough to enable

the perfect coordination of hindered and unhindered sub-

strates,^[5]2) reaction rates increase thanks to the larger p-ac-

ceptor ability of these moieties,^[6]and 3) regioselectivity to-

wards the desired branched isomer in monosubstituted

linear substrates increases, thanks to the p-acceptor ability

of the phosphite moiety that enhances the S_N1 character of

the nucleophilic attack.^[7]

Due to our interest in discovering faster and more versa-

tile Pd-catalytic systems, we decided to go one step further

in the design of a new ligand library for this process. There-

fore, we developed a ligand library, the design of which in-

corporates the advantages of

tions in the biaryl phosphite moiety (a–g). By carefully se-

lecting these elements, we achieved high selectivities (regio-

and enantioselectivities) and activities in a wide range of

mono-, di-, and trisubstituted substrates. In this paper we

also discuss the synthesis and characterization of the Pd–p-

allyl intermediates to provide greater insight into the origin

of enantioselectivity in these catalytic systems.

Results and Discussion

Synthesis of the ligand library: Scheme 1 illustrates the se-

quence of ligand synthesis. Ligands L1–L8a–g were synthe-

sized very efficiently from the corresponding easily accessi-

ble ketone–oxazole or thiazole–ester derivatives (2–5 and

12, Scheme 1). Compounds 2–5 and 12 are easily made in

hetACHTUNGTRENNUNGerodonor and biaryl phos-

phite ligands and also allows

extra control of the flexibility

of the chiral pocket by changing

the size of the chelate ring. To

do this, we synthesized and

screened a library of 56 poten-

tial new phosphite–oxazole/

thiazole ligands.^[8]The highly

modular construction of these

ligands enabled

a systematic

study of the effect of bridge

length (ligands L1 and L6), the

substituent at the heterocyclic

ring (ligands L1–L4) and in the

alkyl backbone chain (ligands

L6 and L7), the configuration

of the ligand backbone (ligands

L1 vs. L5 and L7 vs. L8), and

the substituents and configura-

Scheme 1. Synthesis of a new phosphite–nitrogen ligand library L1–L8a–g. a),b) see ref. [9a] and the Experi-

mental Section; c),d) see ref. [9b]; e) CH₃MgCl/THF/CeCl₃(yield: 71%); f) ClP(OR)₂; (OR)₂=a–g/pyridine/

toluene (yields: 42–76%).

two steps from the corresponding dimedone 1 and ketoester

11, respectively (see the Experimental Section).^[9]Ketone–

oxazoles 2–5 were then reduced using (R)-Me-CBS or

NaBH₄(CBS=oxazaborolidine; Scheme 1, step b). Enantio-

selective reduction of 2 using (R)-Me-CBS followed by

single recrystallization afforded hydroxyl–oxazole

6 in

>99% ee.^[9a]The same procedure applied to ketones 3 and 4

afforded hydroxyl–oxazoles 8 and 9 but with ee values of

<80%. Thus, further enantiomer resolution was achieved

using preparative chiral HPLC. For compounds 7 and 10,

the corresponding ketone–oxazoles 2 and 5 were reduced

using NaBH₄followed by enantiomer resolution using prep-

arative HPLC. Reduction of 12 using LiAlH₄(Scheme 1,

step d)^[9b]or MeMgCl (Scheme 1, step e) gave good yields of

the corresponding racemic alcohols 13 and 14, respectively.

This was followed by the resolution of racemates into their

enantiomers by preparative chiral HPLC.^[9]

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M. Diꢁguez, P. G. Andersson et al.

The last step of the ligand synthesis is common to all of

them (Scheme 1, step f). Therefore, treatment of the corre-

sponding hydroxyl–oxazole (6–10) or hydroxyl–thiazole (13

and 14) with 1 equiv of the corresponding in situ formed

biaryl phosphorochloridite (ClP(OR)₂; (OR)₂=a–g) in the

presence of pyridine, in a parallel manner, provided easy

access to the desired ligands L1–L8a–g (see the Experimen-

tal Section for details). All of the ligands were stable during

purification on neutral alumina under an atmosphere of

argon and isolated in moderate-to-good yields as white

solids. They were stable at room temperature and very

stable to hydrolysis. The elemental analyses were in agree-

tial of the phosphite–nitrogen ligand library L1–L8a–g.

Compound S1 was chosen as a substrate because the reac-

tion was performed with a wide range of ligands, which ena-

bled the efficiency of the various ligand systems to be com-

pared directly.^[1]

First, we studied the effect of the reaction conditions by

conducting a series of experiments with two ligands (L1a

and L6a) using different solvents (tetrahydrofuran, toluene,

and dichloromethane) and ligand-to-palladium ratios (L/

Pd=0.75, L/Pd=1, and L/Pd=2). We found that the effi-

ciency of the process was strongly dependent on the nature

of the solvent and the ligand-to-palladium ratio (Table 1).

1

ment with the assigned structure. The H, ¹³C, and ³¹P NMR

spectra were as expected for these C₁ligands. One singlet

for each compound was observed in the ³¹P NMR spectrum

(see the Experimental Section). Rapid ring inversions (atro-

poisomerization) in the biphenylphosphorus moieties (a–c)

occurred on the NMR spectroscopic timescale because the

expected diastereoisomers were not detected by low-temper-

ature phosphorus NMR spectroscopy.^[10]

Table 1. Selected results for the Pd-catalyzed allylic alkylation of S10 by

using ligand library L1–L8a–g. Effects of the solvent and the ligand-to-

palladium ratio.^[a]

Entry

Ligand

Solvent

L/Pd

Conv [%] (t [min])^[b]

ee [%]^[c]

1

2

3

4

5

6

7

8

9

L1a

L6a

L1a

L6a

CH₂Cl₂

THF

toluene

CH₂Cl₂

THF

toluene

CH₂Cl₂

1

0.75

2

0.75

2

100 (30)

89 (60)

82 (S)

73 (S)

92 (S)

21 (S)

18 (S)

34 (S)

82 (S)

79 (S)

23 (S)

14 (S)

100 (1440)

100 (30)

85 (180)

64 (600)

100 (60)

100 (30)

73 (30)

Allylic substitution of symmetrical 1,3-disubstituted allylic

substrates: In this section, we report the use of the chiral

phosphite–nitrogen ligand library (L1–L8a–g) in the Pd-cat-

alyzed allylic substitution of linear disubstituted substrates

with different steric properties [Eq. (1a)]: rac-1,3-diphenyl-

3-acetoxyprop-1-ene (S1) (widely used as a model sub-

10

100 (30)

[a] All reactions were run at 238C; 0.5 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; S1

strate),

rac-(E)-ethyl-2,5-dimethyl-3-hex-4-enylcarbonate

(0.5 mmol); BSA (N,O-bis(trimethylsilyl)acetamide) (1.5 mmol); dimeth-

yl malonate (1.5 mmol). [b] Conversion measured by ¹H NMR spectros-

copy. Reaction time shown in parentheses. [c] Enantiomeric excesses

measured by HPLC. Absolute configuration shown in parentheses.

(S2), and rac-1,3-dimethyl-3-acetoxyprop-1-ene (S3); and

cyclic substrates [Eq. (1b)]: rac-3-acetoxycyclohexene (S4)

(widely used as a model substrate), rac-3-acetoxycyclohep-

tene (S5), and rac-3-acetoxycyclopentene (S6). Two nucleo-

philes were tested. In all cases, the catalysts were generated

in situ from p-allyl–palladium chloride dimer [{PdCl

(h³-

Although in toluene the enantioselectivity was higher than

dichloromethane, the activity was much lower (Table 1, en-

tries 3 and 6 vs. entries 1 and 4). Tetrahydrofuran yielded

the lowest enantioselectivities of all three solvents (entries 2

and 5). We also found that an excess of ligand was not

needed for enantioselectivities to be high (entries 1, 4, and

7–10). Interestingly, at higher ligand-to-palladium ratios,

enantioselectivities were lower (entries 8 and 10 vs. entries 1

and 4). This is probably due to the fact that at a ligand-to-

palladium ratio greater than 1, the phosphite–nitrogen li-

gands act as a monodentate ligand.^[11]

C₃H₅)}₂] and the corresponding ligand.^[1]

For comparison purposes, the rest of the ligands were

tested using dichloromethane as a solvent and at a ligand-

to-palladium ratio of 1. Table 2 shows the results obtained

when dimethyl malonate and benzylamine were used as nu-

cleophiles. We found that enantioselectivities were highly af-

fected by the bridge length, the substituents at the heterocy-

clic ring and in the alkyl backbone chain, and the substitu-

ents and configurations in the biaryl phosphite moieties (a–

g). High activities (turnover frequencies (TOFs) up to

600 mol S1ꢄ(mol Pdꢄh)^À1) and enantioselectivities (ee

values up to 92%) were obtained for both enantiomers of

the substitution products 15 and 16 using ligands L1a and

L5a. Catalytic performance in the Pd-catalyzed allylic ami-

Allylic substitution of S1 using dimethyl malonate and ben-

zylamine as nucleophiles: In the first set of experiments, we

used the palladium-catalyzed asymmetric substitution reac-

tions of S1 [Eq. (1a); R=Ph, X=OAc], with dimethyl mal-

onate and benzylamine as nucleophiles, to study the poten-

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Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

Table 2. Selected results for the Pd-catalyzed allylic substitution of S1 by using ligand library L1–L8a–g.^[a]

the biaryl moiety and the con-

figuration of the ligand back-

bone on enantioselectivity. This

led to a matched combination

for ligand L1d, which contains

[a]

À

H Nu=H CH

(COOMe)₂

H Nu=H NHCH₂Ph

Entry

Ligand

Conv [%] (t [min])^[b]

ee [%]^[c]

Conv [%] (t [min])^[b]

ee [%]^[c]

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15^[e]

L1a

L1b

L1c

L1d

L1e

L1 f

L1g

L2a

L3a

L4a

L5a

L6a

L7a

L8a

L1a

100 (15)^[d]

99 (20)

82 (S)

81 (S)

70 (S)

69 (S)

40 (S)

9 (S)

34 (360)

37 (360)

43 (360)

28 (360)

31 (360)

15 (360)

12 (360)

24 (360)

36 (360)

19 (360)

32 (360)

41 (360)

38 (360)

33 (360)

–

84 (R)

80 (R)

69 (R)

71 (R)

41 (R)

7 (R)

99 (15)

an

(S)-binaphthyl

moiety

100 (30)^[d]

72 (30)

(Table 2, entries 4 and 5). In ad-

dition, by comparing the results

obtained using ligand L1c with

those of the related binaphthyl

ligands L1d and L1e (Table 2,

entries 3–5), we can also con-

clude that the atropoisomeric

biphenyl moiety in ligands

L1a–c adopts an S configura-

tion when coordinated in the

Pd–p-allyl intermediate species.

To sum up, the best result

was obtained with ligands L1a

and L5a, which contain the op-

timal combination of ligand pa-

42 (30)

8 (R)

5 (S)

80 (30)

43 (S)

79 (S)

22 (S)

81 (R)

21 (S)

52 (S)

51 (R)

92 (S)

32 (R)

82 (R)

25 (R)

84 (S)

19 (R)

49 (R)

50 (S)

–

98 (30)^[d]

78 (30)

100 (15)

100 (20)^[d]

100 (30)^[d]

100 (30)

100 (360)

[a] All reactions were run at 238C; 0.5 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; dichloromethane as solvent; 1 mol% ligand.

1

[b] Conversion measured by H NMR spectroscopy. Reaction time shown in parentheses. [c] Enantiomeric ex-

cesses measured by HPLC. Absolute configuration shown in parentheses. [d] Isolated yields of 15 were

>93%. [e] Toluene as solvent.

nation of S1 followed the same trend as for the allylic alky-

lation of S1 (Table 2). As expected, however, the activity

was lower than in the alkylation reaction of S1. The stereo-

selectivity of the amination was the same as for the alkyla-

tion reaction, though the Cahn–Ingold–Prelog (CIP) de-

scriptor was inverted because the priority of the groups had

changed.

rameters (Table 2, entries 1 and 11). These findings clearly

show the efficiency of highly modular scaffolds in ligand

design. Enantioselectivity can be further improved by con-

trolling not only the structural but also the reaction parame-

ters. As expected, changing the solvent from dichloro-

AHCTUNGTREGmNNUN ethane to toluene increased enantioselectivity (ee values

up to 92%, Table 2, entry 15).

The influence of the bridge length indicates that the use

of ligands L1 and L5, which form a six-membered chelate

ring, provided higher enantioselectivity than the use of li-

gands L6–L8, which form a seven-membered chelate ring

(Table 2, entries 1 and 11 vs. entries 12–14). In line with this,

the increase of the rigidity of the ligand by replacing the hy-

drogen substituents in the alkyl backbone chain in ligand

L6a with two methyl groups (ligand L7a) caused enantiose-

lectivities to increase (Table 2, entries 12 vs. 13).

The effect of the substituents at the heterocyclic ring indi-

cated that the presence of either bulky or electron-donating

substituents decreased both activities and enantioselectivi-

ties (Table 2, entries 1, 8–10). The fact that enantiomeric ex-

cesses decrease when a bulky tert-butyl is present is due to

the formation of Pd intermediate species with the phos-

phite–nitrogen ligand acting as a monodentate ligand (see

below).

Regarding the effect of the substituents at the biphenyl

phosphite moiety, we found that the presence of bulky tert-

butyl substituents at both the ortho and para positions is

highly adventitious in terms of activity and enantioselectivi-

ty (Table 2, entry 1). Therefore, the presence of methoxy

groups in the para position of the biphenyl moieties has a

negative effect on activity, whereas the presence of tri-

Allylic substitution of S2 using dimethyl malonate as nucleo-

phile: We also screened the phosphite–nitrogen ligand li-

brary L1–L8a–g in the allylic alkylation process of S2 using

dimethyl malonate as nucleophile [Eq. (1a); R=iPr, X=

OCO₂Et]. This substrate is more sterically demanding than

substrate S1, which was used previously.^[1]If enantiomeric

excesses are to be high, the ligand must create a slightly

bigger chiral pocket (the chiral cavity in which the allyl is

embedded) around the metal center to be able to accommo-

date the sterically demanding isopropyl substituents.^[1]Due

to the flexibility conferred by the biaryl phosphite moiety,

we expected to obtain good enantioselectivities for this sub-

strate as well. Table 3 shows the most representative results.

In general, the trends were the same as for the allylic substi-

tution of S1. Again, both enantiomers of the alkylation

product 17 were accessible in high enantioselectivities (ee

values up to 93%) when catalyst precursors containing li-

gands L1a and L5a were used (Table 3, entries 1, 9, 13, and

14). As expected, the activities were lower than in the alky-

lation reaction of S1.^[1]The stereoselectivity of the alkyla-

tion of S2 was the same as for the alkylation reaction of S1,

though the CIP descriptor was inverted because of the

change in the priority of the groups.

ACHTUNGTRENNUNGmethylsilyl substituents at the ortho positions has a negative

effect on enantioselectivity (Table 2, entries 2 and 3 vs.

entry 1). With ligands L1d and L1e, which contain different

enantiomerically pure binaphthyl moieties, we found that

there is a cooperative effect between the configuration of

Allylic substitution of S3 using dimethyl malonate as nucleo-

phile: We also tested ligands L1–L8a–g in the allylic substi-

tution of the linear substrate S3 [Eq. (1a); R=Me, X=

OAc]. Substrate S3 is less sterically demanding than sub-

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M. Diꢁguez, P. G. Andersson et al.

Table 3. Selected results for the Pd-catalyzed allylic substitution of S2 by

using ligand library L1–L8a–g.^[a]

Table 4. Selected results for the Pd-catalyzed allylic substitution of S3 by

using ligand library L1–L8a–g.^[a]

Entry

Ligand

Conv [%] (t [h])^[b]

ee [%]^[c]

Entry

Ligand

Conv [%] (t [h])^[b]

ee [%]^[c]

1^[d]

2

3

4

5

L1a

L1b

L1c

L1d

L1e

L2a

L3a

L4a

L5a

L6a

L7a

L8a

L1a

L5a

100 (24)

95 (24)

100 (24)

78 (24)

82 (24)

75 (24)

100 (24)

69 (24)

100 (24)

99 (48)

94 (48)

84 (R)

82 (R)

73 (R)

67 (R)

39 (R)

47 (R)

77 (R)

60 (R)

83 (S)

12 (R)

24 (R)

23 (S)

93 (R)

92 (S)

1^[d]

2

L1a

L1b

L1c

L1d

L1e

L1 f

L1g

L2a

L2e

L3a

L3e

L4a

L5a

L6a

L7a

L7d

L8d

L1d

L7d

100 (1)

100 (2)

82 (2)

59 (S)

67 (S)

54 (S)

75 (S)

51 (S)

30 (S)

21 (S)

60 (S)

74 (S)

59 (S)

75 (S)

5 (S)

57 (R)

38 (S)

80 (S)

87 (S)

87 (R)

84 (S)

92 (S)

3

4^[d]

5^[d]

6

7^[d]

8

7

63 (2)

8^[d]

9^[d]

10^[d]

11^[d]

12^[d]

13

100 (2)

100 (1)

92 (2)

9

10^[d]

11

12

13^[e]

14^[e]

14

15

16

17

93 (3)

[a] All reactions were run at 238C; 1 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; dichloro-

100 (4)

100 (20)

96 (24)

methane as solvent; 2 mol% ligand. [b] Conversion measured by

¹H NMR spectroscopy. Reaction time shown in parentheses. [c] Enantio-

18^[d,e]

19^[e]

1

meric excesses measured by H NMR spectroscopy using [Eu

solute configuration shown in parentheses. [d] Isolated yields of 17 were

>92%. [e] Toluene as solvent.

(hfc)₃]. Ab-

[a] All reactions were run at 238C; 0.5 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; di-

chloromethane as solvent; 1 mol% ligand. [b] Conversion measured by

GC. Reaction time shown in parentheses. [c] Enantiomeric excesses mea-

sured by GC. Absolute configuration shown in parentheses. [d] Isolated

yields of 18 were >91%. [e] T=08C.

strates S1 and S2, used previously. There are therefore

fewer successful catalyst systems for the Pd-catalyzed allylic

substitution of this substrate than for the allylic substitution

of hindered substrates such as S1 and S2.^{[3b,5,6e,11b,12]}If enan-

tiomeric excesses are to be high, the ligand must create a

small chiral pocket around the metal center, mainly because

of the presence of less sterically demanding methyl syn sub-

stituents.^[1]Due to the flexibility conferred by the biaryl

phosphite moiety in combination with the possibility of

changing the size of the chelate ring in the ligand, we ex-

pected to adequately modulate the chiral pocket to obtain

good enantioselectivities for this substrate as well.

Preliminary investigations into the solvent and ligand-to-

palladium ratio revealed a different trend in solvent effect

than with the previously tested substrates S1 and S2. Enan-

tioselectivities and activities were both at their highest when

dichloromethane was used and the ligand-to-palladium ratio

was 1 (see the Supporting Information).

Table 4 shows the results obtained using the ligand library

L1–L8a–g in optimized conditions. We were able to fine-

tune the ligands to obtain high activities and enantioselectiv-

ities (ee values up to 92%) in the alkylation of this sub-

strate. Again, activities and enantioselectivities were affect-

ed by the bridge length, the substituent at the nitrogen het-

erocycle, and the substituents and configurations in the

biaryl phosphite moiety. However, the effect of these pa-

rameters was different from their effect on substitution of

hindered substrates S1 and S2. Enantioselectivities were

best with ligands L7d and L8d (Table 4, entries 16, 17, and

19). Once again, it was possible to access both enantiomers

of the substitution product 18. These results, which again

clearly show the efficiency of using modular scaffolds in

ligand design, are among the best reported for this type of

unhindered substrate.^{[3b,5,6e,11b,12]}

Regarding the effect of ligand flexibility, in contrast to S1

and S2, the highest enantioselectivities were obtained with

ligands L7 and L8, which form a seven-membered chelate

ring and contain two methyl groups at the alkyl backbone

chain. Concerning the effect of the substituents at the het-

AHCTUNGTREGeNNUN rocyclic ring and the biaryl phosphite moiety, in contrast to

S1 and S2, the presence of aryl substituents in the heterocy-

clic moiety and a bulky (S)-binaphthyl phosphite moiety

had a positive effect on enantioselectivities. In conclusion,

our results indicate that both the size of the chelate ring and

the flexibility of the biaryl phosphite moiety are the main

ligand parameters that control the size of the chiral pocket

to achieve high enantioselectivities.

Allylic alkylation of cyclic substrates S4–S6: With the unhin-

dered cyclic substrates S4–S6, enantioselectivity is difficult

to control, mainly because of the presence of less sterically

demanding anti substituents. These anti substituents are

thought to play a crucial role in the enantioselection ob-

served with cyclic substrates in the corresponding Pd–allyl

intermediates.^[1]

In this section, we show that the chiral ligand library L1–

L8a–g that was applied previously to the Pd-catalyzed allylic

substitution of 1,3-disubstituted linear substrates (S1–S3)

can also be used for cyclic substrates (ee values up to 88%).

We tested three cyclic substrates [Eq. (1b)]: rac-3-acetoxycy-

clohexene (S4) (which is widely used as a model substrate),

rac-3-acetoxycycloheptene (S5), and rac-3-acetoxycyclopen-

tene (S6).

Preliminary investigations into the solvent effect and

ligand-to-palladium ratio showed the same trends as with

the previously tested unhindered linear substrate S3. The

624

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A Modular P,N-Ligand Library

FULL PAPER

tradeoff between enantioselectivities and reaction rates was

therefore optimum with dichloromethane and a ligand-to-

palladium ratio of 1 (see the Supporting Information).

Table 5 shows the results of using the ligand library L1–

L8a–g under the optimized conditions. We also obtained

high activities and enantioselectivities (up to 88%) in the al-

Allylic substitution of unsymmetrical 1,3,3-trisubstituted al-

lylic substrate: We also screened the ligands L1–L8a–g in

the allylic substitution of rac-1,3,3-triphenylprop-2-enyl ace-

tate (S7) and rac-1,1-diphenyl-1-hepten-3-yl acetate (S8)

using dimethylmalonate as nucleophile [Eq. (2); R=R’=

R’’=Ph for S7 and R=R’=Ph, R’’=Me for S8]. These sub-

strates are of synthetic interest because the substitution

products formed in this way can easily be transformed into

enantiomerically enriched acid derivatives and lactones.^[14]

They are more sterically demanding than the previously

used substrate S1,^[1]and it is therefore more difficult to ach-

ieve excellent enantioselectivities with them than with

S1.^[12,15]Interestingly, with this P,N-ligand library, we ob-

tained high enantiomeric excesses (ee values up to 96%)

under standard reaction conditions. Although, as expected,

the activities were lower than in the alkylation reaction of

S1, they were much higher than those obtained with other

successful ligands under similar reaction conditions.^[15]

Table 5. Selected results for the Pd-catalyzed allylic substitution of S4–S6

by using ligand library L1–L8a–g.^[a]

Entry

Substrate

Ligand

Conv [%] (t [h])^[b]

ee [%]^[c]

1

2

3

S4

S5

S6

L1a

L1b

L1c

L1d

L1e

L2a

L3a

L3e

L4a

L5a

L6a

L7a

L7d

L1d

L1e

L1d

L1e

100 (6)

100 (24)

100 (6)

41 (S)

59 (S)

43 (S)

80 (S)

85 (R)

41 (S)

45 (S)

84 (R)

60 (S)

39 (R)

13 (S)

29 (S)

63 (S)

83 (S)

88 (R)

72 (S)

71 (R)

4^[d]

5^[d]

6

7

8^[d]

9^[d]

10

11

12

13

14

15^[d]

16

17

[a] All reactions were run at 238C; 0.5 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; di-

chloromethane as solvent; 1 mol% ligand. [b] Conversion measured by

GC. Reaction time shown in parentheses. [c] Enantiomeric excesses mea-

sured by GC. Absolute configuration shown in parentheses. [d] Isolated

yields of 19 and 20 were >91%.

The results, summarized in Table 6, followed a trend similar

to that of the more hindered substrates S1 and S2. Thus, li-

gands L1 and L5, which form a six-membered chelate ring

and have a phenyl substituent at the nitrogen heterocycle,

provided better enantioselectivities than ligands L2–L4 and

L6–L8. The presence of bulky substituents at the ortho posi-

tions of the biaryl phosphite moiety was necessary for enan-

tioselectivities to be high. However, in contrast to S1 and

S2, enantioselectivities were less affected by the presence or

lack of bulky substituents at the para positions of the biaryl

phosphite moiety. Therefore, ligands L1a–c and L5a–c pro-

lylic substitution of the cyclic substrates S4–S6 using ligands

L1d, L1e, and L3e. The results indicate that the effect of

the ligand parameters on the catalytic performance are dif-

ferent from those observed for the linear substrates S1–S3.

In contrast to the alkylation of unhindered linear S3, ligands

that form a six-membered chelate ring (L1) provided higher

enantioselectivities than those that form a seven-membered

chelate ring (L6, L7). The results also indicate that the pres-

ence of an enantiopure bulky binaphthyl phosphite moiety

(d and e) is therefore required for enantioselectivity to be

high (Table 5, entries 4, 5, 8, 14, and 15). Interestingly, the

sense of enantioselectivity is also governed by the configura-

tion of the biaryl phosphite moiety. Thus, both enantiomers

of the substitution products 19–21 can be accessed in high

enantioselectivities by simply changing the configuration of

the trimethylsilyl-substituted binaphthyl moiety (Table 5, en-

tries 4 and 5).

In summary, the enantioselectivities obtained with ligands

L1d, L1e, and L3e are among the best reported for this

type of 1,3-disubstituted cyclic substrate.^{[1e,3a,5a,11b,12a,13]}Inter-

estingly, compared with the hindered substrates S1 and S2

and in contrast to the unhindered linear substrate S3, the

flexibility conferred by the biaryl phosphite moiety was

enough to adequately control the size of the chiral pocket to

achieve high enantioselectivities.

Table 6. Selected results for the Pd-catalyzed allylic substitution of S7

and S8 by using ligand library L1–L8a–g.^[a]

S7

Entry Ligand Conv [%] (t

[h])^[b]

S8

ee

Conv [%] (t

ee

[%]^[c]

[h])^[b]

[%]^[c]

1^[d]

2

3

4

5

6

7

8

9

L1a

L1b

L1c

L1d

L1g

L2a

L3a

L4a

L5a

L6a

L7a

L8a

92 (24)

88 (24)

79 (24)

46 (24)

33 (24)

90 (24)

88 (24)

45 (24)

88 (24)

67 (24)

29 (24)

27 (24)

88 (R)

95 (R)

96 (R)

42 (R)

18 (R)

81 (R)

90 (R)

23 (R)

90 (S)

40 (R)

30 (R)

30 (S)

100 (24)

53 (24)

48 (24)

100 (24)

85 (24)

100 (24)

73 (24)

46 (24)

42 (24)

95 (R)

94 (R)

95 (R)

32 (R)

21 (R)

78 (R)

85 (R)

38 (R)

95 (S)

57 (R)

44 (R)

42 (S)

10

11

12

[a] All reactions were run at 238C; 1 mol% [{PdClACTHNUTRGNEUNG

(h³-C₃H₅)}₂]; dichloro-

methane as solvent; 2 mol% ligand. [b] Conversion measured by

¹H NMR spectroscopy. Reaction time shown in parentheses. [c] Enantio-

meric excesses measured by ¹H NMR spectroscopy. Absolute configura-

tion shown in parentheses. [d] Isolated yields of 22 and 23 were >88%.

Chem. Eur. J. 2010, 16, 620 – 638

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625

M. Diꢁguez, P. G. Andersson et al.

vided excellent enantiocontrol in the allylic substitution of

the trisubstituted substrates S7 and S8, and also gave access

to both enantiomers of the alkylation products 22 and 23 (ee

values up to 96%). These results are among the best report-

ed for this class of substrate.^[15]

up to 92%) combined with regioselectivities of up to 80%

in favor of the branched product 24 were obtained under

standard reaction conditions. The results indicate that the

selectivity (regio- and enantioselectivity) is mainly affected

by the ligand backbone, the substituent at the nitrogen het-

erocycle, and the substituents and configurations in the

biaryl phosphite moiety. However, no general trend was

seen. The tradeoff between regio- and enantioselectivities

was best for ligand L7a, which forms a seven-membered

chelate ring and has methyl substitutents at the alkyl-back-

bone chain and bulky tert-butyl groups at the ortho and para

positions of the biphenyl phosphite moiety (Table 7, en-

tries 14 and 19). Again, these

Allylic substitution of unsymmetrical 1- or 3-monosubstitut-

ed allylic substrates: To further study the potential of these

readily available ligands, we tested L1–L8a–g in the regio-

and stereoselective allylic alkylation of 1-(1-naphthyl)allyl

acetate (S9) and 1-(1-naphthyl)-3-acetoxyprop-1-ene (S10)

with dimethyl malonate as nucleophile [Eq. (3)].

results are among the best re-

ported for this type of sub-

AHCTUNGTRENNUNG

strate.^{[5a,7,11b,17]}

Origin of enantioselectivity—

study of the Pd–p-allyl inter-

mediates: To provide further in-

sight into how ligand parame-

ters affect catalytic perfor-

mance, we studied the Pd–p-

For these substrates, not only does the enantioselectivity of

the process need to be controlled but regioselectivity is also

a problem because a mixture of regioisomers can be ob-

tained. Most Pd catalysts developed to date favor the forma-

tion of achiral linear product 25 rather than the desired

branched isomer 24.^[16]The development of highly regio-

and enantioselective Pd catalysts is therefore still importan-

t.^{[5a,7,11b,17]}

allyl compounds 26–35 [PdACTHGNUTERNNUG

(h³-allyl)(L)]BF₄(L=L1–L8a–g),

because they are key intermediates in the allylic substitution

reactions studied.^[1]These ionic palladium complexes, which

contain 1,3-diphenyl-, 1,3-dimethyl-, or cyclohexenylallyl

groups, were prepared using the previously reported method

from the corresponding Pd–allyl dimer and the appropriate

ligand in the presence of silver tetrafluoroborate

(Scheme 2).^[18]The complexes were characterized by ele-

Table 7 summarizes the results obtained with the ligand li-

brary L1–L8a–g. High activities and enantioselectivities (of

Table 7. Selected results for the Pd-catalyzed allylic alkylation of mono-

substituted substrates S9 and S10 by using ligand library L1–L8a–g under

standard conditions.^[a]

Entry Ligand Substrate Conv [%] (t [min])^[b]24/25^[c]ee [%]^[d]

1

2

3

4

L1a

L1b

L1c

L1d

L1e

L2a

L2d

L3a

L3c

L4a

L6a

L7a

L7d

L1d

L3c

L2d

L7a

S9

100 (30)

70:30

40:60

55:45

50:50

55:45

80:20

75:25

70:30

75:25

45:55

80:20

60:40

50:50

70:30

75:25

80:20

20 (R)

63 (R)

70 (R)

78 (R)

34 (R)

45 (R)

88 (R)

19 (R)

73 (R)

25 (R)

2 (S)

92 (R)

90 (R)

79 (R)

72 (R)

87 (R)

92 (R)

5

Scheme 2. Preparation of [PdACHTNUGRTNEUNG

(h³-allyl)(L)]BF₄complexes 26–35.

6^[e]

7

8

9

10

11

14

15

16

17

18

19

mental analysis and by H, ¹³C, and ³¹P NMR spectroscopy.

The spectral assignments (see the Experimental Section)

were based on information from ¹H,¹H, ³¹P, ¹H and ¹³C,¹H

correlation measurements in combination with ¹H,¹H

NOESY experiments. Unfortunately, we were unable to

obtain crystals of sufficient quality to perform X-ray diffrac-

tion measurements. For some of the key Pd–allyl complexes,

we also performed a DFT study.

1

S9

S10

[a] All reactions were run at 238C; 1 mol% [{PdClACTHNUTRGNEUNG

((h³-C₃H₅)}₂]; dichloro-

methane as solvent; 2 mol% ligand; substrate (0.5 mmol); BSA

(1.5 mmol); dimethyl malonate (1.5 mmol). [b] Reaction time in minutes

shown in parentheses. [c] Percentage of branched (24) and linear (25) iso-

mers. [d] Enantiomeric excesses of 24 determined by HPLC. Absolute

configuration shown in parentheses. [e] Isolated yield of 24 was >72%.

Palladium 1,3-diphenylallyl complexes: When the phos-

phite–nitrogen ligand library L1–L8a–g was used in the al-

lylic substitution of substrate S1, the catalytic results showed

that enantioselectivity is highly affected by the ligand pa-

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A Modular P,N-Ligand Library

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rameters. A six-membered chelate ring, phenyl substituents

in the nitrogen heterocyclic ring, and bulky substituents at

the ortho position of the biaryl moiety are therefore re-

quired if enantioselectivity is to be high. To understand this

catalytic behavior, we studied the Pd–p-allyl complexes 26–

28, which contain ligands L1a, L6a, and L4a, respectively.

Finally, with complexes 29 and 30, which contain ligands

L1d and L1e, we studied the cooperative effect seen be-

tween the configuration of the ligand backbone and the con-

figuration of the biaryl phosphite moiety.

The variable temperature (VT) NMR (30 to À808C) spec-

troscopic study of the Pd–allyl intermediate 26, which con-

tains ligand L1a, had a mixture of two isomers in equilibri-

um at a ratio of 9:1 (see the Experimental Section).^[19]Both

isomers were unambiguously assigned by NMR spectrosco-

py (¹H, ³¹P, ¹³C, ¹H,¹H, ¹H,¹³C, and ¹H,³¹P correlation and

NOESY experiments) to the two syn/syn endo A and exo B

isomers (Scheme 3). In both isomers, the NOE indicated in-

Figure 1. Calculated structures (DFT) for cationic species of complex

[Pd(h³-1,3-diphenylallyl)

ACTHNUGTRNE(NUG L1a)]BF₄(26) and their relative formation en-

thalpies. This figure also shows the relevant NOE contacts from the

NOESY experiment.

of the different Pd-allyl intermediates formed in solution.

For both isomers, the carbon NMR spectroscopic chemical

shifts indicate that the more electrophilic allyl carbon termi-

nus is trans to the phosphite moiety (Scheme 3). Assuming

that the nucleophilic attack takes place at the more electro-

philic allyl carbon terminus,^[1]the matching between enan-

tiomeric excesses (82% S in product 15) and the diastereo-

isomeric Pd ratio (de=80% (S)) indicate that the two iso-

mers react at a similar rate. This is in agreement with the

fact that the electrophilicities of the allylic terminal carbon

atom trans to the phosphite are rather similar in both com-

plexes (DACTHNUTRGNEUNG

(d¹³C)=0.5 ppm). To prove this, we studied the re-

activity of the Pd intermediates with sodium malonate at

low temperature by in situ NMR spectroscopy (see the Sup-

porting Information). Our results showed that the two iso-

mers react at a similar rate.

The VT NMR spectroscopic study of Pd–allyl intermedi-

ate 27 containing ligand L6a, which forms a seven-mem-

bered chelate ring and provides lower enantioselectivity

than Pd/L1a, also had a mixture of two syn/syn endo (A)

and exo (B) isomers, but at a ratio of 1.25:1 (see the Experi-

mental Section). Also, the more electrophilic allyl carbon

terminus was trans to the phosphite moiety (Scheme 4). In

contrast to the Pd/L1a catalytic system, the diastereoisomer-

ic excess (de=11% (S)) of the Pd intermediates differed

from the enantiomeric excess (21% (S)) of alkylation prod-

uct 15. As shown by NMR spectroscopy,^[20]isomer A reacts

slightly faster than isomer B,^[21]thus explaining this differ-

ence. However, the lower enantioselectivity with this system

than with the previous Pd/L1a catalytic system can mainly

be attributed to the decrease in the relative amount of

isomer A with respect to isomer B, compared with the popu-

lation of the isomers (A and B) for complex 26.

Next, we studied the Pd–1,3-diphenylallyl intermediate 28

containing ligand L4a, which differs from L1a due to the

presence of a bulky tert-butyl group at the oxazole moiety

instead of a phenyl substituent and provides much lower

enantioselectivity than the Pd/L1a catalyst. The VT NMR

spectra indicated the presence of a mixture of two species at

a ratio of 7:3 (see the Experimental Section). The major

species were assigned by NOE to the syn/syn endo A

isomer, whereas the minor species was attributed to com-

Scheme 3. Diastereoisomer Pd–allyl intermediates for S1 with ligand

L1a. The relative amounts of each isomer are shown in parentheses. The

chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

teractions between the two terminal protons of the allyl

group and also between the central allyl proton and ortho-

hydrogen atoms of both phenyl groups of the allyl ligand,

which clearly indicates a syn/syn disposition (Figure 1).

Moreover, the central allyl proton showed a NOE interac-

À

tion with the hydrogen of the CH O group of the ligand

backbone of the major isomer A, whereas in isomer B this

interaction appeared with the hydrogen atoms of one tert-

butyl group. These interactions can be explained by assum-

ing a syn/syn endo disposition for isomer A and a syn/syn

exo disposition for isomer B (Figure 1). We also carried out

theoretical calculations at the DFT level for both isomers.

Figure 1 shows these calculated structures and the relative

values of the formation enthalpy, with isomer A being the

most stable. The difference in the calculated formation en-

thalpy for the two isomers (DH=1.8 kcalmol^À1) is in agree-

ment with the population observed by NMR spectroscopy

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627

M. Diꢁguez, P. G. Andersson et al.

pound C, which contains two ligands coordinated in a mono-

dentated fashion (Scheme 5).^[22]The formation of C is due

to the fact that the replacement of the phenyl ozaxole sub-

stituents in ligand L1a by a bulky tert-butyl group caused

greater steric interaction with one of the phenyl substitu-

tents of substrate S1 in the related syn/syn exo B isomer ob-

served in Pd/L1a complex 26 (Scheme 5). The formation of

compound C minimizes this new steric interaction and ex-

plains why the expected syn/syn exo B isomer in solution

was not detected (Scheme 5). Therefore, the fact that enan-

tioselectivity was lower when the Pd/L4a catalyst was used

(ee values up to 22%) than when the Pd/L1a catalyst was

used (ee values up to 82%) may be due to the presence of

Pd complex C. Complexes of this type are known to be

faster and less enantioselective than their bidentate counter-

parts because they have more degrees of freedom.^[11b,23]

Finally, we studied the cooperative effect observed be-

tween the configuration of the ligand backbone and the con-

figuration of the biaryl phos-

Scheme 4. Diastereoisomer Pd–allyl intermediates for S1 with ligand

L6a. The relative amounts of each isomer are shown in parentheses. The

chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

phite moiety with complexes 29

and 30, which contain ligands

L1d and L1e, respectively. The

VT NMR spectroscopic study

indicated the presence of a mix-

ture of two syn/syn endo (A)

and exo (B) isomers in ratios of

5:1 and 1:2.5, respectively

(Scheme 6). As for the 1,3-di-

phenylallyl intermediates dis-

cussed above, the NMR spec-

troscopic data showed that the

more electrophilic allyl terminal

carbon is trans to the phosphite

moiety at the A isomers (29A

Scheme 5. Diastereoisomer Pd–allyl intermediates for S1 with ligand L4a. The relative amounts of each

isomer are shown in parentheses. The chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

and 30A). For complex 29, our

results indicated that the ste-

reochemical outcome of the re-

Scheme 6. Diastereoisomer Pd–allyl intermediates for S1 with a) ligand L1d and b) ligand L1e. The relative amounts of each isomer are shown in paren-

theses. The chemical shifts (in ppm) of the allylic terminal carbon atoms are also shown.

628

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Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

action (ee=69% (S)) was mainly due to the diastereoiso-

meric excess (de=66% (S)) of the Pd complexes in solu-

tion, as observed for Pd/L1a. However, for complex 30, the

diastereoisomeric excess (de=43% (R)) did not match the

enantioselectivity obtained (ee=40% (S)). Therefore, we

conclude that isomer 30A reacts faster than isomer 30B. A

clear indication of this fact can be found in the higher elec-

trophilicity of the allylic terminal carbon trans to the phos-

ligand L1a, had a mixture of three isomers in equilibrium at

a ratio of 2.5:1:2 (see the Experimental Section). Isomers A

and B were assigned by NOE to the two syn/syn endo A

and exo B isomers, whereas isomer D was assigned to the

syn/anti isomer (Scheme 7). For isomers A and B, the NOE

indicated interactions between the two terminal protons of

the allyl group, whereas for isomer D the central allyl

proton showed a NOE interaction with the terminal allyl

proton located trans to the oxazole group (Figure 2). More-

over, for isomers A and D, the central allyl proton showed a

phite in 30A than in 30B (DACHTNUTGRNEUNG

(d¹³C)=4.6 ppm). Although

isomer 30A has a faster reaction rate than isomer 29A, this

is not the reason why Pd/L1e causes lower enantioselectivity

than Pd/L1d. Rather, the lower enantioselectivity of Pd/L1e

is because the relative amount of isomer A respect to

isomer B is much lower in Pd/L1e than in Pd/L1d. There-

fore, as observed earlier, the presence of an S configuration

at the biaryl phosphite moiety is necessary for good enantio-

selectivity. In addition, these results provide further evi-

dence that the flexible biphenyl phosphite moieties in li-

gands L1a–c adopt an S configuration when coordinated to

palladium.

In summary, the study of the Pd–1,3-diphenylallyl inter-

mediate showed that for enantioselectivity to be high, the

different ligand parameters need to be correctly combined

to predominantly form one of the Pd isomers and also to

avoid the formation of species

À

NOE interaction with the hydrogen of the CH O group of

the ligand, whereas in isomer B this interaction appeared

with the hydrogen atoms of the tert-butyl group. These inter-

actions can be explained by assuming a syn/syn endo dispo-

sition for isomer A, a syn/syn exo disposition for isomer B,

and a syn/anti disposition for isomer D (Figure 2). The

NOESY also indicated an exchange between the allylic ter-

minal protons located trans to the oxazole moiety of isomers

B and D (Figure 2). This confirms the h³–h¹–h³movement

for the exchange between isomers B and D.^[24]In addition,

the fact that no other H_anti–H_synexchange was observed indi-

cates that the exchange took place by means of the selective

À

opening of one of the terminal Pd C bonds. The formation

of isomer D is due to the fact that, in complex B, there was

with ligands coordinated in a

monodentated fashion.

Palladium–1,3-dimethylallyl

complexes: When the phos-

phite–nitrogen ligand library

L1–L8a–g was used in the allyl-

ic substitution of substrate S3,

the catalytic results revealed a

different trend with regard to

the effect of the ligand parame-

ters than with the hindered sub-

strate S1. A seven-membered

chelate ring, the presence of

methyl substituents at the alkyl

backbone chain, and a bulky

Scheme 7. Diastereoisomer Pd–allyl intermediates for S3 with ligand L1a. The relative amounts of each

isomer are shown in parentheses. The chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

(S)-binaphthyl

phosphite

moiety are necessary for high

enantioselectivity. To under-

stand this catalytic behavior, we

studied Pd–p-allyl complexes

31–33, which contain ligands

L1a, L7a, and L7e, respective-

ly. With ligands L1a and L7a,

we studied the effect of the che-

late ring size, whereas with

ligand L7e we studied the con-

figuration of the biaryl phos-

phite moiety.

The VT NMR (30 to À808C)

Figure 2. Relevant NOE contacts from the NOESY experiment of the [Pd(h³-1,3-dimethylallyl)

ACTHNUGTRNE(NUG L1a)]BF₄(31)

spectroscopic study of Pd–allyl

intermediate 31, which contains isomers.

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629

M. Diꢁguez, P. G. Andersson et al.

an increase in the steric interaction between the oxazole

phenyl group and one of the methyl substitutents of S3 due

to the absence of the favorable p-stacking interaction ob-

served in the related Pd–1,3-diphenylallyl complex 26. The

formation of isomer D minimized this steric interaction

lectivity with this system than with the Pd/L1a catalytic

system discussed above can be attributed to the decrease in

the relative amount of isomer B with respect to isomer A

compared with the population of the isomers (A and B) for

complex 31. The decrease in the population of isomer B is

due to the formation of a smaller chiral pocket with ligand

L7a than with ligand L1a. This smaller chiral pocket creates

a greater steric interaction between the thiazole phenyl

group and one of the methyl substitutents of S3, which re-

sults in the preferential formation of the less electrophilic

syn/anti isomer D.

Finally, the VT NMR spectroscopic study of Pd–allyl in-

termediate 33, which contains ligand L7d, had a mixture of

three isomers in a ratio of 10:1:9 (see the Experimental Sec-

tion). Isomers A, B, and D were assigned by NOE to the

syn/syn endo, syn/syn exo, and syn/anti isomers, respectively

(Scheme 9). As for complexes 31 and 32, the fastest-reacting

isomer was the syn/syn isomer A, whereas isomer D was far

less electrophilic and therefore did not play a direct role in

À

(Scheme 7). Therefore, the open Pd C bond belongs to the

most electrophilic carbon atom containing the substituent

that undergoes the biggest steric hindrance with the phenyl

oxazole fragment. The NMR spectroscopic data also indicat-

ed that the most electrophilic allyl carbon terminus is trans

to the phosphite moiety in syn/syn isomer A and in syn/syn

isomer B, and that the allylic terminus carbon in isomer D is

far less electrophilic (DACHTNUGRTNEUNG

(d¹³C)>11 ppm). Assuming that the

nucleophilic attack takes place at the most electrophilic allyl

carbon terminus, on the basis of the observed stereochemi-

cal outcome of the reaction (59% S in product 18), and

since the ee of alkylation product 18 differs from the diaste-

reoisomeric excess (de=41% (S)) of the reacting Pd inter-

mediates A and B, we conclude that isomer A reacts faster

than isomer B. This was con-

firmed by an in situ NMR spec-

troscopic study of the reactivity

of the Pd intermediates with

sodium malonate at low tem-

perature. This study indicated

that isomer 31A reacts approxi-

mately 1.5 times faster than

isomer 31B. This is also consis-

tent with the fact that, for both

isomers, the most electrophilic

allylic terminal carbon atom is

the one trans to the phosphite

in the major A isomer.

The VT NMR spectroscopic

study of Pd–allyl intermediate

32, which contains ligand L7a,

Scheme 8. Diastereoisomer Pd–allyl intermediates for S3 with ligand L7a. The relative amounts of each

isomer are shown in parentheses. The chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

which forms a seven-membered

chelate ring and provides

higher enantioselectivity than

Pd/L1a, also had a mixture of

three isomers at a ratio of 5:1:7

(see the Experimental Section).

Isomers A, B, and D were as-

signed by NOE to the syn/syn

endo, syn/syn exo, and syn/anti

isomers,

respectively

(see

Scheme 8). Again, the most

electrophilic allyl carbon termi-

nus was trans to the phosphite

moiety in syn/syn isomer A and

syn/syn isomer B, and the allylic

terminus carbon in isomer D

was far less electrophilic (D-

ACHTUNGTRENNUNG

A

Scheme 9. Diastereoisomer Pd–allyl intermediates for S3 with ligand L7d. The relative amounts of each

isomer B. The higher enantiose- isomer are shown in parentheses. The chemical shifts (in ppm) of the allylic terminal carbon atoms are shown.

630

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Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

the enantiodiscrimination process. The higher enantioselec-

tivity obtained with Pd/L7d than with the Pd/L7a catalytic

system is due to the larger amount of the most reactive

isomer (isomer A) than in com-

plex 32.

by NOE to the isomers A and B (Figure 3). Thus, for isomer

A, the NOE indicated interactions between the hydrogen of

À

the CH O group and the central allyl proton, whereas for

In summary, for enantioselec-

tivities to be high, the various

ligand parameters need to be

correctly combined to preferen-

tially form the faster isomer A.

The formation of this isomer is

mainly governed by the size of

the chelate ring and the config-

uration of the biaryl phosphite

moiety.

Palladium–1,3-cyclohexenylallyl

complexes: When the phos-

Figure 3. Calculated structures (DFT) for cationic species of complex [Pd(h³-1,3-cyclohexenylallyl)

(34) and their relative formation enthalpies. This figure also shows the relevant NOE contacts from the

ACHTUNGTRENNUNG(L1a)]BF₄

phite–nitrogen ligand library NOESY experiment.

L1–L8a–g was used in the allyl-

ic substitution of cyclic sub-

strates S5 and S6, the catalytic results showed that the effect

of the ligand parameters on enantioselectivity was different

from the effect observed in the substitution of the linear

substrates S1 and S2. The best results were obtained with li-

gands L1d and L1e, which form a six-membered chelate

ring, have phenyl substituents in the nitrogen heterocyclic

ring, and have bulky enantiopure binaphthyl phosphite moi-

eties. Interestingly, the sense of enantioselectivity was con-

trolled by the configuration of the biaryl phosphite moiety.

So, to understand this catalytic behavior, we studied Pd–p-

allyl complexes 34 and 35, which contain ligands L1d and

L1e.

isomer B this interaction appeared with one of the methyl-

enic hydrogen atoms of the allyl ligand (Figure 3). The

carbon NMR spectroscopic chemical shifts indicated that

the most electrophilic allylic terminus carbon is trans to the

phosphite moiety. The difference between the diastereoiso-

meric ratio and enantioselectivity observed in the alkylation

of S5 (de=70% (S) vs. ee=80% (S)) indicated that the nu-

cleophile reacts faster with the major B isomer. This was

confirmed by the reactivity of the Pd intermediate with

sodium malonate at low temperature by in situ NMR spec-

troscopy.^[25]We also carried out theoretical calculations at

the DFT level. Figure 3 shows these calculated structures

and their relative formation enthalpy values, with isomer B

being the most stable. The difference in the calculated for-

mation enthalpies of the two isomers (DH=1.5 Kcalmol^À1)

is in agreement with the population observed by NMR spec-

troscopy.

The VT NMR (35 to À808C) spectroscopic study of Pd in-

termediate 34, which contains ligand L1d, showed a mixture

of the two possible isomers at a ratio of 1:6, respectively

(see Scheme 10). All isomers were unambiguously assigned

The VT NMR (358C to À808C) spectroscopic study of Pd

intermediate 35, which contains ligand L1e, also showed a

mixture of the two possible isomers (A and B), but at a

ratio of 6.5:1, respectively (Scheme 11). The carbon NMR

spectroscopic chemical shifts also indicated that the most

electrophilic allylic terminus carbon is trans to the phosphite

moiety. In contrast to Pd intermediate 34, the fastest-react-

ing isomer is A. This is in agreement with the fact that Pd/

L1e provided a level of enantioselectivity similar to that of

Pd/L1d, discussed above, but in the opposite enantiomer of

the alkylation products 19 and 20.

Conclusion

A new P,N-ligand library L1–L8a–g was synthesized for the

Pd-catalyzed allylic substitution reactions of several sub-

strates with different electronic and steric properties. These

series of ligands have five main advantages: 1) they can be

Scheme 10. Diastereoisomer Pd–allyl intermediates for S5 with ligand

L1d. The relative amounts of each isomer are shown in parentheses. The

chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

Chem. Eur. J. 2010, 16, 620 – 638

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

631

M. Diꢁguez, P. G. Andersson et al.

Experimental Section

General considerations: All reactions were carried out using standard

Schlenk techniques under an atmosphere of argon. Solvents were purified

and dried by standard procedures. Phosphorochloridites are easily pre-

pared in one step from the corresponding biaryls.^[26]Hydroxyl–oxazoles 6

and 7 and hydroxyl–thiazole 13 were prepared as previously described.^[9]

Racemic substrates S1–S10 were prepared as previously reported.^{[27–30,14b]}

[{Pd(h³-1,3-Ph₂-C₃H₃)

[{Pd(h³-cyclohexenyl)

G

(m-Cl)}₂],^[32]and

ACHTUNGTRENNUNG

AHCTUNGTRENNUNG

¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectra were recorded using a 400 MHz

spectrometer. Chemical shifts are relative to that of SiMe₄(¹H and ¹³C)

as internal standard or H₃PO₄(³¹P) as external standard. ¹H, ¹³C, and ³¹P

assignments were done based on ¹H,¹H gCOSY, ¹H,¹³C gHSQC, and

¹H,³¹P gHMBC experiments. Geometries of all substrates were optimized

using the Jaguar program^[34]by applying the B3LYP hybrid density func-

tional^[35]together with the LACVP** basis sets. Normal-mode analysis of

stable structures revealed no imaginary frequencies, or a single imaginary

frequency with negligibly low energy (n˜ <100 cm^À1). LACVP in Jaguar

defines a combination of the LANL2DZ basis set^[36]for palladium and

the 6-31G basis set for other atoms.

Scheme 11. Diastereoisomer Pd–allyl intermediates for S5 with ligand

L1e. The relative amounts of each isomer are shown in parentheses. The

chemical shifts (in ppm) of the allylic terminal carbon atoms are also

shown.

General procedure for the preparation of hydroxyl–oxazoles 8 and 9: Di-

azodimedone (2.00 g, 12 mmol) and the corresponding para-substituted

benzonitrile (60 mmol for 4-methylbenzonitrile and 14 mmol for 4-(tri-

fluoromethyl)benzonitrile) were heated in an oil bath at 608C and Rh-

AHCTUNGTRENNUNG

ACHTUNGTRENNUNG

prepared efficiently from readily available hydroxyl–oxa-

zole/thiazole derivatives; 2) the hydroxyl–oxazole/thiazole

cores are much more robust than the usually used hydroxyl–

oxazoline ones; 3) the flexibility and larger bite angle creat-

ed by the biaryl phosphite moiety and the different bridge

lengths increase versatility; 4) the p-acceptor character of

the phosphite moiety increases reaction rates; and 5) their

modular nature enables the bridge length, the substituents

at the heterocyclic ring and in the alkyl backbone chain, the

configuration of the ligand backbone, and the substituents/

configurations in the biaryl phosphite moiety to be easily

and systematically varied, so that activities and regio- and

enantioselectivities can be maximized for each substrate as

required. By carefully selecting the ligand components,

therefore, high regio- and enantioselectivities (ee values up

to 96%) and good activities were obtained in a broad range

of mono-, di-, and trisubstituted linear hindered and unhin-

dered substrates and cyclic substrates. Of particular note

were the high regio- and enantioselectivities (up to 96% ee)

combined with high activities obtained for the mono- and

trisubstituted substrates S7–S10. In addition, for all sub-

strates, both enantiomers of the substitution products were

obtained with high enantioselectivities.

By studying the Pd–1,3-diphenylallyl, –1,3-dimethylallyl,

and –1,3-cyclohexenylallyl intermediates by means of NMR

spectroscopy and DFT calculations, we were able to better

understand the observed catalytic behavior. For enantiose-

lectivities to be high, we conclude that ligand parameters

need to be correctly combined to predominantly form the

Pd intermediate that has the fastest reaction with the nucle-

ophile. We also found that the nucleophilic attack takes

place predominantly at the allylic terminal carbon atom lo-

cated trans to the phosphite moiety.

(10 mg, 0.045 mmol) was added. After an additional 1.5 h, the reaction

was cooled to room temperature and purified by chromatography on

silica (pentane/ethyl acetate 75:25 to 25:75) to give the ketone–oxazoles

as white solids. Compound 3 (2.02 g, 66% yield): ¹H NMR (CDCl₃): d=

1.21 (s, 6H; 2ꢄCH₃), 2.41 (s, 3H; CH₃), 2.50 (s, 2H; CH₂), 2.90 (s, 2H;

CH₂), 7.24–7.29 (m, 2H; Ar), 7.97–8.02 ppm (m, 2H; Ar). Compound 4

(1.53 g, 51% yield): ¹H NMR (CDCl₃): d=1.22 (s, 6H; 2ꢄCH₃), 2.52 (s,

2H; CH₂), 2.93 (s, 2H; CH₂), 7.71–7.75 (m, 2H; Ar), 8.20–8.25 ppm (m,

2H; Ar).

For the reduction of the ketone–oxazoles, BH₃·SMe₂(2.1 equiv) and (R)-

Me-CBS (0.1 equiv) were dissolved in THF (5 mL for 4 mmol BH₃·SMe₂)

at 08C and stirred for 1 h. The temperature was raised to ambient and a

solution of ketone (1 equiv) in THF/toluene (4:1 mL for 2 mmol ketone)

was added over 2 h using a syringe pump. The reaction was stirred for an

additional hour, cooled to 08C, and quenched with methanol. The solvent

was evaporated and the resulting oil was purified by chromatography on

silica (pentane/ethyl acetate 25:75) to afford hydroxyl–oxazoles 8 and 9

as white solids (72% ee for 8 and 78% ee for 9). The enantiomeric excess

could not be increased by recrystallization. The enantiomers were sepa-

rated by chiral chromatography on semipreparative HPLC using a 250ꢄ

20 mm Chiralcel OD column (hexane/isopropanol 95:5, 5 mLmin^À1) to

give ee>99%. Hydroxyl–oxazole 8: ¹H NMR (CDCl₃): d=1.03 (s, 3H;

CH₃), 1.19 (s, 3H; CH₃), 1.67 (dd, J=13.2, 8.0 Hz, 1H; CH₂), 1.99 (ddd,

À

J=13.4, 6.0, 1.5 Hz, 1H; CH₂), 2.38 (s, 3H; CH₃Ph), 2.45 (m, 1H; CH₂),

2.59 (dd, J=16.4, 2.2 Hz, 1H; CH₂), 3.66 (brs, 1H; OH), 4.85 (m, 1H;

CH), 7.18–7.28 (m, 2H; CH=), 7.87–7.95 ppm (m, 2H; CH=); ¹³C NMR

(CDCl₃): d=24.5, 26.9, 30.6, 33.0, 35.6, 45.5, 62.9, 124.9, 126.1, 129.4,

136.0, 140.3, 147.3, 161.3 ppm; elemental analysis calcd (%) for

C₁₆H₁₉NO₂: C 74.68, H 7.44, N 5.44; found: C 74.47, H 7.50, N 5.43. Hy-

droxyl–oxazole 9: ¹H NMR (CDCl₃): d=1.05 (s, 3H; CH₃), 1.21 (s, 3H;

CH₃), 1.68 (dd, J=13.3, 8.1 Hz, 1H; CH₂), 2.02 (dd, J=13.3, 6.0 Hz, 1H;

CH₂), 2.50 (d, J=16.8 Hz, 1H; CH₂), 2.63 (d, J=16.8 Hz, 1H; CH₂), 3.27

(brs, 1H; OH), 4.87 (m, 1H; CH), 7.63–7.74 (m, 2H; CH=), 8.07–

8.18 ppm (m, 2H; CH=); ¹³C NMR (CDCl₃): d=27.2, 30.8, 33.3, 35.9,

45.7, 63.2, 126.0, 126.1, 126.6, 131.0, 137.0, 149.0, 160.0 ppm; elemental

analysis calcd (%) for C₁₆H₁₆F₃NO₂: C 61.73, H 5.18, N 4.50; found: C

61.79, H 5.23, N 4.52.

Preparation of hydroxyl–oxazole 10: Diazodimedone (5.00 g, 30.1 mmol),

pivalonitrile (12.5 g, 150 mmol), and RhACTHNUTRGNENUG(OAc)₂(27 mg, 0.12 mmol) were

heated in an oil bath at 608C. The reaction was stirred for 1 h, cooled to

room temperature, and purified by chromatography on silica (pentane/

632

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Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

À

ethyl acetate 75:25 to 25:75) to give ketone–oxazole 5 as a white solid

(4.23 g, 68% yield). ¹H NMR (CDCl₃): d=1.16 (s, 6H; 2ꢄCH₃), 1.39 (s,

9H; 3ꢄCH₃), 2.41 (s, 2H; CH₂), 2.78 ppm (s, 2H; CH₂).

O), 3.29 (s, 3H; CH₃O), 5.52 (m, 1H; CH O), 6.7–8.2 ppm (m, 9H;

CH=); ¹³C NMR (C₆D₆): d=27.8 (CH₃), 29.2 (CH₃), 30.0 (CMe₂), 31.6

À

(CH₃, tBu), 31.8 (CH₃, tBu), 33.0 (C, tBu), 35.6 (CH₂C=), 45.1 (CH₂),

55.4 (CH₃O), 55.5 (CH₃O), 67.9 (d, J

156 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

C₃₇H₄₄NO₆P: C 70.57, H 7.04, N 2.22; found: C 70.52, H 7.09, N 2.31.

Ligand L1c: Yield: 722 mg (59%); ³¹P NMR (C₆D₆): d=147.8 ppm;

H NMR (C₆D₆): d=0.44 (s, 9H; CH₃Si), 0.55 (s, 9H; CH₃Si), 0.59 (s,

3H; CH₃), 0.81 (s, 3H; CH₃), 1.58 (m, 1H; CH₂), 1.76 (m, 1H; CH₂),

1.96 (m, 1H; CH₂C=), 2.13 (m, 1H; CH₂C=), 5.50 (m, 1H; CH O),

6.9–8.3 ppm (m, 11H; CH=); C NMR (C₆D₆): d=0.8 (CH₃Si), 0.9

(CH₃Si), 27.9 (CH₃), 30.2 (CH₃), 33.2 (CMe₂), 35.9 (CH₂C=), 45.3

(C,P)=8.4 Hz; CH O), 123–150 ppm (aromatic carbon

atoms); elemental analysis calcd (%) for C₃₃H₄₀NO₄PSi₂: C 65.86, H 6.70,

N 2.33; found: C 65.92, H 6.72, N 2.31.

Ligand L1d: Yield: 698 mg (49%); ³¹P NMR (C₆D₆): d=146.3 ppm;

H NMR (C₆D₆): d=0.45 (s, 3H; CH₃), 0.54 (s, 9H; CH₃Si), 0.73 (s, 9H;

CH₃Si), 0.82 (s, 3H; CH₃), 1.57 (m, 1H; CH₂), 1.88 (m, 1H; CH₂), 2.11

À

(C,P)=13 Hz; CH O), 126–

For the reduction of the ketone–oxazole, ketone (2.22 g, 10 mmol) was

dissolved in 95% ethanol (125 mL), and NaBH₄(1.14 g, 30 mmol) was

added. The reaction was stirred and followed by TLC. The reaction was

quenched with 1m HCl and extracted with dichloromethane (2ꢄ25 mL).

The organic phase was dried over MgSO₄, filtered, and concentrated to

give racemic hydroxyl–oxazole 10 as a white solid (1.94 g, 87% yield).

The enantiomers were separated by chiral chromatography on semipre-

parative HPLC using a (250ꢄ20 mm) Chiralcel OD column (hexane/iso-

propanol 98:2, 5 mLmin^À1) to give ee>99%. ¹H NMR (CDCl₃): d=0.96

(s, 3H; CH₃), 1.11 (s, 3H; CH₃), 1.32 (s, 9H; CH₃, tBu), 1.57 (dd, J=3.2,

8.0 Hz, 1H; CH₂), 1.86 (ddd, J=13.2, 5.9, 1.4 Hz, 1H; CH₂), 2.30 (dt, J=

16.2, 1.6 Hz, 1H; CH₂), 2.45 (dd, J=16.2, 2.1 Hz, 1H; CH₂), 4.52 (brs,

1H; OH), 4.74 ppm (m, 1H; CH); ¹³C NMR (CDCl₃): d=26.8, 28.5, 30.5,

30.6, 32.9, 33.7, 35.4, 45.5, 62.0, 62.2, 134.2, 146.4, 170.4 ppm; elemental

analysis calcd (%) for C₁₃H₂₁NO₂: C 69.92, H 9.48, N 6.27; found: C

69.89, H 9.52, N 6.22.

1

À

13

À

(CH₂), 67.8 (d, J

U

1

À

(m, 2H; CH₂C=), 5.02 (m, 1H; CH O), 6.9–8.3 ppm (m, 15H; CH=);

C NMR (C₆D₆): d=0.5 (CH₃Si), 1.0 (CH₃Si), 27.9 (CH₃), 29.7 (CH₃),

13

À

Preparation of hydroxyl–thiazole 14: CeCl₃·7H₂O (3.15 g) was dried in a

À

32.8 (CMe₂), 35.6 (CH₂C=), 45.5 (CH₂), 70.2 (CH O), 123–161 ppm (ar-

omatic carbon atoms); elemental analysis calcd (%) for C₄₁H₄₄NO₄PSi₂:

C 70.15, H 6.32, N 2.00; found: C 70.22, H 6.35, N 2.01.

vacuum oven at 1208C overnight.

A flask with dry CeCl₃(2.00 g,

8.10 mmol) was cooled under nitrogen in an ice bath, THF was added

(30 mL), and the suspension was stirred at room temperature overnight.

Ligand L1e: Yield: 536 mg (39%); ³¹P NMR (C₆D₆): d=147.4 ppm;

H NMR (C₆D₆): d=0.33 (s, 3H; CH₃), 0.55 (s, 9H; CH₃Si), 0.65 (s, 3H;

After cooling in an ice bath,

a 3m solution of MeMgCl (4 mL,

1

À

12.0 mmol) was added. Suspension was stirred for 2 h and a solution of

thiazole ester^[9b](0.65 g, 2.26 mmol) was added in THF (10 mL). After

stirring overnight, the reaction was cooled in an ice bath and quenched

by addition of saturated NH₄Cl solution (50 mL), and stirred for 1 h.

Water (50 mL) was added, THF was evaporated, and the product was ex-

tracted with diethyl ether (2 times). After drying the organic phase over

MgSO₄, filtering, and evaporation of the solvent, crude material was puri-

fied by chromatography on silica (pentane/ethyl acetate 100:0 to 95:5) to

give hydroxyl–thiazole 14 as a white solid (0.44 g, 71% yield). The reso-

lution of enantiomers was achieved on semipreparative HPLC using a

(250ꢄ20 mm) Chiralcel OD column (hexane/isopropanol 95:5,

5 mLmin^À1) to give both enantiomers with ee>99%. ¹H NMR (CDCl₃):

d=1.01 (s, 3H; CH₃), 1.32 (s, 3H; CH₃), 1.39 (m, 1H; CH₂), 1.74 (m,

1H; CH₂), 2.02–2.15 (m, 2H; CH₂), 2.73 (m, 1H; CH₂), 2.85 (m, 1H;

CH₂), 2.99 (m, 1H; CH₂), 6.48 (brs, 1H; OH), 7.33–7.46 (m, 2H; CH=),

7.80–7.92 ppm (m, 2H; CH=); ¹³C NMR (CDCl₃): d=23.1, 23.8, 24.2,

26.2, 27.7, 48.4, 73.5, 126.1, 128.8, 129.8, 131.1, 133.1, 152.4, 164.2 ppm; el-

emental analysis calcd (%) for C₁₆H₁₉NOS: C 70.29, H 7.00, N 5.12;

found: C 70.35, H 7.02, N 5.11.

À

CH₃), 0.68 (s, 9H; CH₃Si), 1.34 (m, 1H; CH₂), 1.61 (m, 1H; CH₂), 1.89

À

(m, 1H; CH₂C=), 2.06 (m, 1H; CH₂C=), 5.49 (m, 1H; CH O), 6.9–

13

À

8.3 ppm (m, 15H; CH=); C NMR (C₆D₆): d=0.3 (CH₃Si), 0.4 (CH₃

Si), 26.5 (CH₃), 29.6 (CH₃), 32.4 (CMe₂), 35.1 (CH₂C=), 44.3 (CH₂), 66.8

À

(d, J

(C,P)=7.2 Hz; CH O), 123–160 ppm (aromatic carbon atoms); ele-

mental analysis calcd (%) for C₄₁H₄₄NO₄PSi₂: C 70.15, H 6.32, N 2.00;

found: C 70.19, H 6.29, N 1.97.

Ligand L1 f: Yield: 712 mg (64%); ³¹P NMR (C₆D₆): d=138.7 ppm;

¹H NMR (C₆D₆): d=0.42 (s, 3H; CH₃), 0.78 (s, 3H; CH₃), 1.48 (dd, ²J-

3

2

3

U

ACHTUGTNRENG(NU H,H)=5.6 Hz, 1H; CH₂), 1.71 (dd, JCAHTUNGTRENNNUG

À

G

(H,H)=16 Hz, 1H; CH₂C=), 2.06

(d, ²J

(H,H)=16 Hz, 1H; CH₂C=), 5.34 (m, 1H; CH O), 6.9–8.3 ppm

À

(m, 17H; CH=); ¹³C NMR (C₆D₆): d=28.0 (CH₃), 29.4 (CH₃), 32.7

À

(CH₂C=), 35.7 (CMe₂), 45.2 (CH₂), 68.5 (d, JACHTNUTRGNEUNG(C,P)=4.7 Hz; CH O),

122–162 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

C₃₅H₂₈NO₄P: C 75.39, H 5.06, N 2.51; found: C 75.42, H 5.11, N 2.50.

Ligand L1g: Yield: 849 mg (76%); ³¹P NMR (C₆D₆): d=153.1 ppm;

¹H NMR (C₆D₆): d=0.51 (s, 3H; CH₃), 0.72 (s, 3H; CH₃), 1.50 (dd, ²J-

(H,H)=12.4 Hz, ³J(H,H)=5.6 Hz, 1H; CH₂), 1.59 (dd, ²J

AHCTUNGTREUNNGN ACHTUNGTRENNUNG ACHTUNGTRENNUNG

General procedure for the preparation of phosphite–nitrogen ligands L1–

L8a–g: Phosphorochloridite (2.2 mmol) produced in situ was dissolved in

toluene (5 mL) and pyridine (0.36 mL, 4.6 mmol) was added. Hydroxyl–

oxazole or hydroxyl–thiazole (2 mmol) was azeotropically dried with tol-

uene (3ꢄ1 mL) and then dissolved in toluene (10 mL), to which pyridine

(0.36 mL, 4.6 mmol) was added. The alcohol solution was transferred

slowly at 08C to the solution of phosphorochloridite. The reaction mix-

ture was warmed up to 808C and stirred overnight, and the pyridine salts

were removed by filtration. Evaporation of the solvent gave a white

foam, which was purified by flash chromatography (toluene/hexane/

NEt₃) to produce the corresponding ligand as a white powder.

12.4 Hz, ³J(H,H)=7.2 Hz, 1H; CH₂), 1.92 (m, ²J

ACTHNUGTRENNUGN ACHTUNGTRENNNUG

CH₂C=), 2.01 (d, ²J

U

À

O), 6.8–8.3 ppm (m, 17H; CH=); ¹³C NMR (C₆D₆): d=28.1 (CH₃), 29.7

À

(CH₃), 32.8 (CH₂C=), 35.6 (CMe₂), 45.0 (d, J

A

À

(d, J

(C,P)=20.1 Hz; CH O), 122–162 ppm (aromatic carbon atoms); ele-

mental analysis calcd (%) for C₃₅H₂₈NO₄P: C 75.39, H 5.06, N 2.51;

found: C 75.35, H 5.13, N 2.48.

Ligand L2a: Yield: 587 mg (42%); ³¹P NMR (C₆D₆): d=148.0 ppm;

¹H NMR (C₆D₆): d=0.78 (s, 3H; CH₃), 0.98 (s, 3H; CH₃), 1.44 (s, 9H;

CH₃, tBu), 1.46 (s, 9H; CH₃, tBu), 1.79 (m, 1H; CH₂), 1.83 (s, 9H; CH₃,

tBu), 1.91 (s, 9H; CH₃, tBu), 1.95 (m, 1H; CH₂), 2.19 (m, 2H; CH₂C=),

2.28 (m, 3H; CH₃Ph), 5.75 (m, 1H; CH O), 7.1–8.4 ppm (m, 8H;

CH=); C NMR (C₆D₆): d=21.7 (CH₃Ph), 27.8 (CH₃), 30.0 (CH₃), 31.9

(CH₃, tBu), 32.0 (CH₃, tBu), 33.1 (C, tBu), 36.2 (CH₂C=), 36.7 (CMe₂),

Ligand L1a: Yield: 826 mg (60%); ³¹P NMR (C₆D₆): d=148.7 ppm;

¹H NMR (C₆D₆): d=0.57 (s, 3H; CH₃), 0.77 (s, 3H; CH₃), 1.23 (s, 9H;

CH₃, tBu), 1.25 (s, 9H; CH₃, tBu), 1.57 (m, 1H; CH₂), 1.61 (s, 9H; CH₃,

À

13

À

tBu), 1.69 (s, 9H; CH₃, tBu), 1.73 (m, 1H; CH₂), 1.92 (m, 1H; CH₂C=),

À

2.08 (m, 1H; CH₂C=), 5.53 (m, 1H; CH O), 7.1–8.2 ppm (m, 9H;

45.1 (CH₂), 67.9 (d, J

carbon atoms); elemental analysis calcd (%) for C₄₄H₅₈NO₄P: C 75.94, H

(C,P)=17 Hz; CH O), 124–164 ppm (aromatic

CH=); ¹³C NMR (C₆D₆): d=27.7 (CH₃), 29.9 (CH₃), 31.9 (CH₃, tBu), 33.1

À

(C, tBu), 35.0 (CH₂C=), 36.2 (CMe₂), 45.1 (CH₂), 67.8 (d, J

G

8.40, N 2.01; found: C 75.89, H 8.41, N 2.0.5.

À

Ligand L2d: Yield: 698 mg (49%); ³¹P NMR (C₆D₆): d=146.3 ppm;

12.2 Hz; CH O), 124–165 ppm (aromatic carbon atoms); elemental anal-

ysis calcd (%) for C₄₃H₅₆NO₄P: C 75.74, H 8.28, N 2.05; found: C 75.82,

H 8.11, N 2.11.

1

À

H NMR (C₆D₆): d=0.43 (s, 3H; CH₃), 0.51 (s, 9H; CH₃Si), 0.70 (s, 9H;

À

CH₃Si), 0.80 (s, 3H; CH₃), 1.52 (m, 1H; CH₂), 1.72 (m, 1H; CH₂), 2.18

Ligand L1b: Yield: 725 mg (58%); ³¹P NMR (C₆D₆): d=148.6 ppm;

¹H NMR (C₆D₆): d=0.60 (s, 3H; CH₃), 0.82 (s, 3H; CH₃), 1.55 (s, 9H;

CH₃, tBu), 1.62 (s, 9H; CH₃, tBu), 1.77 (m, 1H; CH₂), 1.80 (m, 1H;

À

(m, 2H; CH₂C=), 2.23 (m, 3H; CH₃Ph), 5.11 (m, 1H; CH O), 6.9–

13

À

8.3 ppm (m, 15H; CH=); C NMR (C₆D₆): d=0.4 (CH₃Si), 0.6 (CH₃

À

Si), 20.9 (CH₃Ph), 27.8 (CH₃), 29.2 (CH₃), 33.8 (CMe₂), 35.8 (CH₂C=),

À

CH₂), 1.97 (m, 1H; CH₂C=), 2.12 (m, 1H; CH₂C=), 3.28 (s, 3H; CH₃

45.6 (CH₂), 69.8 (CH O), 123–161 ppm (aromatic carbon atoms); ele-

Chem. Eur. J. 2010, 16, 620 – 638

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

633

M. Diꢁguez, P. G. Andersson et al.

mental analysis calcd (%) for C₄₂H₄₆NO₄PSi₂: C 70.46, H 6.48, N 1.96;

found: C 70.52, H 6.49, N 2.00.

ysis calcd (%) for C₄₃H₅₆NO₄P: C 75.74, H 8.28, N 2.05; found: C 75.72,

H 8.31, N 2.01.

Ligand L2e: Yield: 623 mg (44%); ³¹P NMR (C₆D₆): d=146.9 ppm;

Ligand L6a: Yield: 738 mg (54%); ³¹P NMR (C₆D₆): d=137.9 ppm;

¹H NMR (C₆D₆): d=1.43 (s, 9H; CH₃, tBu), 1.48 (s, 9H; CH₃, tBu), 1.76

(m, 2H; CH₂), 1.82 (s, 9H; CH₃, tBu), 1.87 (s, 9H; CH₃, tBu), 2.00 (m,

1

À

H NMR (C₆D₆): d=0.49 (s, 3H; CH₃), 0.510 (s, 9H; CH₃Si), 0.66 (s,

À

9H; CH₃Si), 0.76 (s, 3H; CH₃), 1.69 (m, 2H; CH₂), 2.21 (m, 2H; CH₂

À

C=), 2.25 (m, 3H; CH₃Ph), 5.16 (m, 1H; CH O), 6.9–8.3 ppm (m, 15H;

2H; CH₂CH), 2.46 (m, 2H; CH₂C=), 3.36 (m, 1H; CH), 4.48 (m, 1H;

13

CH=); C NMR (C₆D₆): d=À0.2 (CH₃Si), 0.1 (CH₃Si), 21.1 (CH₃

CH₂O), 4.83 (m, 1H; CH₂O), 7.2–8.2 ppm (m, 9H; CH=); ¹³C NMR

À

Ph), 27.9 (CH₃), 29.5 (CH₃), 33.9 (CMe₂), 36.2 (CH₂C=), 45.3 (CH₂),

(C₆D₆): d=21.4 (CH₂), 23.9 (CH₂C=), 26.1 (CH₂CH), 31.8 (CH₃, tBu),

35.0 (C, tBu), 36.1 (C, tBu), 39.1 (CH), 67.3 (CH₂O), 125–165 ppm (aro-

matic carbon atoms); elemental analysis calcd (%) for C₄₂H₅₄NO₃PS: C

À

70.1 (CH O), 123–161 ppm (aromatic carbon atoms); elemental analysis

calcd (%) for C₄₂H₄₆NO₄PSi₂: C 70.46, H 6.48, N 1.96; found: C 70.49, H

6.51, N 1.99.

73.76, H 7.96, N 2.05; found: C 73.86, H 7.99, N 2.08.

Ligand L3a: Yield: 674 mg (45%); ³¹P NMR (C₆D₆): d=147.8 ppm;

¹H NMR (C₆D₆): d=0.61 (s, 3H; CH₃), 0.81 (s, 3H; CH₃), 1.28 (s, 9H;

CH₃, tBu), 1.29 (s, 9H; CH₃, tBu), 1.60 (m, 1H; CH₂), 1.65 (s, 9H; CH₃,

Ligand L6b: Yield: 598 mg (48%); ³¹P NMR (C₆D₆): d=137.5 ppm;

¹H NMR (C₆D₆): d=1.33 (m, 2H; CH₂), 1.54 (s, 9H; CH₃, tBu), 1.59 (s,

À

9H; CH₃, tBu), 1.82 (m, 2H; CH₂CH), 2.27 (m, 2H; CH₂C=), 3.15 (m,

À

tBu), 1.74 (s, 9H; CH₃, tBu), 1.77 (m, 1H; CH₂), 1.97 (m, 1H; CH₂C=),

1H; CH), 3.29 (s, 3H; CH₃O), 3.33 (s, 3H; CH₃O), 4.33 (m, 1H;

2.12 (m, 1H; CH₂C=), 5.55 (m, 1H; CH O), 7.0–8.1 ppm (m, 8H;

CH₂O), 4.71 (m, 1H; CH₂O), 6.7–8.1 ppm (m, 9H; CH=); ¹³C NMR

À

CH=); ¹³C NMR (C₆D₆): d=27.6 (CH₃), 30.0 (CH₃), 31.9 (CH₃, tBu), 32.0

(C₆D₆): d=21.7 (CH₂), 23.9 (CH₂C=), 26.3 (CH₂CH), 31.3 (CH₃, tBu),

À

(CH₃, tBu), 33.1 (CMe₂), 35.0 (C, tBu), 35.7 (C, tBu), 36.2 (CH₂C=),

31.4 (CH₃, tBu), 35.9 (C, tBu), 36.0 (C, tBu), 39.2 (CH), 55.4 (CH₃O),

À

45.0 (CH₂), 67.5 (d, J

A

67.7 (CH₂O), 112–165 ppm (aromatic carbon atoms); elemental analysis

carbon atoms); elemental analysis calcd (%) for C₄₄H₅₅F₃NO₄P: C 70.47,

calcd (%) for C₃₆H₄₂NO₅PS: C 68.44, H 6.70, N 2.22; found: C 68.48, H

6.72, N 2.20.

H 7.39, N 1.87; found: C 70.57, H 7.42, N 1.89.

Ligand L3c: Yield: 593 mg (44%); ³¹P NMR (C₆D₆): d=146.8 ppm;

Ligand L6c: Yield: 640 mg (53%); ³¹P NMR (C₆D₆): d=136.5 ppm;

1

À

H NMR (C₆D₆): d=0.39 (s, 9H; CH₃Si), 0.49 (s, 9H; CH₃Si), 0.53 (s,

3H; CH₃), 0.77 (s, 3H; CH₃), 1.52 (m, 1H; CH₂), 1.69 (m, 1H; CH₂),

H NMR (C₆D₆): d=0.44 (s, 9H; CH₃Si), 0.52 (s, 9H; CH₃Si), 1.36 (m,

À

1H; CH₂), 1.56 (m, 1H; CH₂), 1.79 (m, 2H; CH₂CH), 2.27 (m, 2H;

À

1.95 (m, 1H; CH₂C=), 2.12 (m, 1H; CH₂C=), 5.42 (m, 1H; CH O),

CH₂C=), 3.15 (m, 1H; CH), 4.15 (m, 1H; CH₂O), 4.68 (m, 1H; CH₂

O), 6.9–8.2 ppm (m, 11H; CH=); C NMR (C₆D₆): d=0.7 (CH₃Si), 0.8

(CH₃Si), 21.8 (CH₂), 24.2 (CH₂C=), 26.5 (CH₂CH), 39.3 (CH), 67.8

(CH₂O), 125–165 ppm (aromatic carbon atoms); elemental analysis

13

À

6.9–8.1 ppm (m, 10H; CH=); C NMR (C₆D₆): d=0.9 (CH₃Si), 1.0

À

(CH₃Si), 27.7 (CH₃), 30.3 (CH₃), 33.2 (CMe₂), 35.9 (CH₂C=), 45.0

(C,P)=6.1 Hz; CH O), 124–160 ppm (aromatic carbon

atoms); elemental analysis calcd (%) for C₃₄H₃₉F₃NO₄PSi₂: C 60.97, H

À

(CH₂), 67.5 (d, J

U

calcd (%) for C₃₂H₃₈NO₃PSSi₂: C 63.65, H 6.34, N 2.32; found: C 63.68,

H 6.36, N 2.35.

5.87, N 2.09; found: C 60.99, H 5.89, N 2.07.

Ligand L3e: Yield: 676 mg (43%); ³¹P NMR (C₆D₆): d=146.3 ppm;

Ligand L6d: Yield: 647 mg (47%); ³¹P NMR (C₆D₆): d=136.2 ppm;

1

À

H NMR (C₆D₆): d=0.43 (s, 3H; CH₃), 0.51 (s, 9H; CH₃Si), 0.62 (s, 3H;

H NMR (C₆D₆): d=0.58 (s, 9H; CH₃Si), 0.59 (s, 9H; CH₃Si), 1.36 (m,

À

CH₃), 0.65 (s, 9H; CH₃Si), 1.34 (m, 1H; CH₂), 1.56 (m, 1H; CH₂), 1.84

2H; CH₂), 1.72 (m, 2H; CH₂CH), 2.32 (m, 2H; CH₂C=), 2.94 (m, 1H;

À

(m, 1H; CH₂C=), 2.02 (m, 1H; CH₂C=), 5.42 (m, 1H; CH O), 6.8–

CH), 3.96 (m, 1H; CH₂O), 4.76 (m, 1H; CH₂O), 6.9–8.3 ppm (m,

13

À

À À

8.1 ppm (m, 14H; CH=); C NMR (C₆D₆): d=1.0 (CH₃Si), 1.1 (CH₃

15H; CH=); C NMR (C₆D₆): d=À0.3 (CH₃Si), À0.1 (CH₃Si), 21.3

À

Si), 27.0 (CH₃), 30.3 (CH₃), 33.2 (CMe₂), 35.8 (CH₂C=), 45.0 (CH₂), 67.2

(CH₂), 23.2 (CH₂C=), 25.8 (CH₂CH), 38.4 (d, JACHTNGUTERNNU(G C,P)=3.2 Hz; CH),

À

(d, J

(C,P)=5.3 Hz; CH O), 123–160 ppm (aromatic carbon atoms); ele-

mental analysis calcd (%) for C₄₂H₄₃F₃NO₄PSi₂: C 65.52, H 5.63, N 1.82;

67.1 (CH₂O), 122–164 ppm (aromatic carbon atoms); elemental analysis

calcd (%) for C₄₀H₄₂NO₃PSSi₂: C 68.24, H 6.01, N 1.99; found: C 68.21,

H 5.98, N 1.97.

found: C 65.34, H 5.59, N 1.86.

Ligand L4a: Yield: 652 mg (49%); ³¹P NMR (C₆D₆): d=148.0 ppm;

¹H NMR (C₆D₆): d=0.59 (s, 3H; CH₃), 0.80 (s, 3H; CH₃), 1.28 (s, 9H;

CH₃, tBu), 1.29 (s, 9H; CH₃, tBu), 1.40 (s, 9H; CH₃, tBu), 1.56 (m, 1H;

CH₂), 1.66 (s, 9H; CH₃, tBu), 1.71 (s, 9H; CH₃, tBu), 1.75 (m, 1H; CH₂),

Ligand L6e: Yield: 605 mg (43%); ³¹P NMR (C₆D₆): d=136.3 ppm;

1

À

H NMR (C₆D₆): d=0.61 (s, 9H; CH₃Si), 0.73 (s, 9H; CH₃Si), 1.31 (m,

À

1H; CH₂), 1.45 (m, 1H; CH₂), 1.63 (m, 1H; CH₂CH), 1.88 (m, 1H;

À

CH₂CH), 2.16 (m, 2H; CH₂C=), 3.21 (m, 1H; CH), 4.16 (m, 1H;

1.98 (m, 1H; CH₂C=), 2.14 (m, 1H; CH₂C=), 5.52 (m, 1H; CH O),

7.0–7.7 ppm (m, 4H; CH=); ¹³C NMR (C₆D₆): d=27.8 (CH₃), 29.2 (CH₃),

29.9 (CH₃, tBu), 32.0 (CH₃, tBu), 32.2 (CH₃, tBu), 33.1 (CMe₂), 34.4 (C,

CH₂O), 4.43 (m, 1H; CH₂O), 6.8–8.4 ppm (m, 15H; CH=); ¹³C NMR

À

(C₆D₆): d=À0.2 (CH₃Si), À0.1 (CH₃Si), 20.6 (CH₂), 23.0 (CH₂C=),

À

25.6 (CH₂CH), 38.1 (d,

JACTHNGUETRNUN(G C,P)=4.0 Hz; CH), 67.1 (CH₂O), 122–

À

tBu), 35.0 (C, tBu), 36.1 (CH₂C=), 36.2 (C, tBu), 45.3 (CH₂), 68.1 (d, J-

164 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

À

A

C₄₀H₄₂NO₃PSSi₂: C 68.24, H 6.01, N 1.99; found: C 68.27, H 6.03, N 2.02.

Ligand L7a: Yield: 598 mg (42%); ³¹P NMR (C₆D₆): d=151.4 ppm;

¹H NMR (C₆D₆): d=1.19 (s, 3H; CH₃), 1.24 (s, 9H; CH₃, tBu), 1.26 (s,

9H; CH₃, tBu), 1.50 (s, 9H; CH₃, tBu), 1.53 (s, 3H; CH₃), 1.62 (s, 9H;

analysis calcd (%) for C₄₁H₆₀NO₄P: C 74.40, H 9.14, N 2.12; found: C

74.45, H 9.18, N 2.08.

Ligand L4c: Yield: 709 mg (61%); ³¹P NMR (C₆D₆): d=148.2 ppm;

1

À

H NMR (C₆D₆): d=0.49 (s, 9H; CH₃Si), 0.54 (s, 9H; CH₃Si), 0.57 (s,

CH₃, tBu), 1.89 (m, 2H; CH₂), 2.12 (m, 2H; CH₂CH), 2.28 (m, 2H;

CH₂C=), 3.16 (m, 1H; CH), 7.0–8.0 ppm (m, 9H; CH=); ¹³C NMR

À

3H; CH₃), 0.78 (s, 3H; CH₃), 1.21 (s, 9H; CH₃, tBu), 1.45 (m, 1H; CH₂),

À

1.69 (m, 1H; CH₂), 1.96 (m, 1H; CH₂C=), 2.19 (m, 1H; CH₂C=), 5.48

(C₆D₆): d=22.4 (CH₂), 24.3 (CH₂C=), 26.4 (CH₂CH), 27.9 (CH₃), 30.4

(CH₃), 31.4 (CH₃, tBu), 31.6 (CH₃, tBu), 31.8 (CH₃, tBu), 35.1 (C, tBu),

36.3 (C, tBu), 36.4 (C, tBu), 40.3 (CH), 71.0 (CMe₂), 124–166 ppm (aro-

matic carbon atoms); elemental analysis calcd (%) for C₄₄H₅₈NO₃PS: C

74.23, H 8.21, N 1.97; found: C 74.31, H 8.24, N 1.93.

13

À

(m, 1H; CH O), 6.9–7.8 (m, 6H; CH=); C NMR (C₆D₆): d=0.2 (CH₃

À

Si), 0.4 (CH₃Si), 27.9 (CH₃), 29.8 (CH₃), 30.2 (CH₃, tBu), 33.2 (CMe₂),

36.3 (CH₂C=), 45.5 (CH₂), 68.3 (d,

155 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

C₃₁H₄₄NO₄PSi₂: C 63.99, H 7.62, N 2.41; found: C 64.03, H 7.65, N 2.39.

À

JACTHNGUTRENNU(G C,P)=10 Hz; CH O), 123–

Ligand L7d: Yield: 638 mg (42%); ³¹P NMR (C₆D₆): d=143.2 ppm;

Ligand L5a: Yield: 843 mg (62%); ³¹P NMR (C₆D₆): d=148.7 ppm;

¹H NMR (C₆D₆): d=0.57 (s, 3H; CH₃), 0.77 (s, 3H; CH₃), 1.23 (s, 9H;

CH₃, tBu), 1.25 (s, 9H; CH₃, tBu), 1.57 (m, 1H; CH₂), 1.61 (s, 9H; CH₃,

H NMR (C₆D₆): d=0.53 (s, 9H; CH₃Si), 0.56 (s, 9H; CH₃Si), 1.14 (s,

1

À

3H; CH₃), 1.50 (s, 3H; CH₃), 1.77 (m, 2H; CH₂), 2.09 (m, 2H; CH₂

CH), 2.25 (m, 2H; CH₂C=), 3.17 (m, 1H; CH), 7.0–8.0 ppm (m, 15H;

À

13

À

tBu), 1.69 (s, 9H; CH₃, tBu), 1.73 (m, 1H; CH₂), 1.92 (m, 1H; CH₂C=),

CH<C=>); C NMR (C₆D₆): d=À0.3 (CH₃Si), À0.1 (CH₃Si), 22.1

À

2.08 (m, 1H; CH₂C=), 5.53 (m, 1H; CH O), 7.1–8.2 ppm (m, 9H;

(CH₂), 23.8 (CH₂C<C=>), 25.9 (CH₂CH), 27.8 (CH₃), 29.9 (CH₃),

CH=); ¹³C NMR (C₆D₆): d=27.7 (CH₃), 29.9 (CH₃), 31.9 (CH₃, tBu), 33.1

39.9 (CH), 70.3 (CH₂O), 122–166 ppm (aromatic carbon atoms); ele-

mental analysis calcd (%) for C₄₄H₅₀NO₃PSSi₂: C 69.53, H 6.63, N 1.84;

found: C 69.55, H 6.64, N 1.80.

À

(C, tBu), 35.0 (CH₂C=), 36.2 (CMe₂), 45.1 (CH₂), 67.8 (d, J

(C,P)=

À

12.2 Hz; CH O), 124–165 ppm (aromatic carbon atoms); elemental anal-

634

www.chemeurj.org

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

Ligand L8a: Yield: 798 mg (56%); ³¹P NMR (C₆D₆): d=151.4 ppm;

¹H NMR (C₆D₆): d=1.24 (s, 9H; CH₃, tBu), 1.26 (s, 9H; CH₃, tBu), 1.50

(s, 9H; CH₃, tBu), 1.53 (s, 3H; CH₃), 1.62 (s, 9H; CH₃, tBu), 1.89 (m,

35.3 (C, tBu), 35.5 (C, tBu), 39.2 (CH), 70.0 (CH₂O), 77.2 (m; CH allyl

À

trans to N), 96.2 (m; CH trans to P), 112.0 (m; CH allyl central), 125–

165 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

C₅₇H₆₇BF₄NO₃PPdS: C 63.96, H 6.31, N 1.31; found: C 64.03, H 6.32, N

1.33.

À

2H; CH₂), 2.12 (m, 2H; CH₂CH), 2.28 (m, 2H; CH₂C=), 3.16 (m, 1H;

CH), 7.0–8.0 ppm (m, 9H; CH=); ¹³C NMR (C₆D₆): d=22.4 (CH₂), 24.3

À

Complex 28: Isomer A (70%): ³¹P NMR (CD₂Cl₂, 233 K): d=139.2 ppm

(s, 1P); ¹H NMR (CD₂Cl₂, 233 K): d=0.62 (s, 3H; CH₃), 0.89 (s, 3H;

CH₃), 1.31 (s, 18H; CH₃, tBu), 1.43 (s, 9H; CH₃, tBu), 1.54 (s, 9H; CH₃,

tBu), 1.69 (m, 1H; CH₂), 1.74 (s, 9H; CH₃, tBu), 1.86 (m, 1H; CH₂), 2.01

(CH₂C=), 26.4 (CH₂CH), 27.9 (CH₃), 30.4 (CH₃), 31.4 (CH₃, tBu), 31.6

(CH₃, tBu), 31.8 (CH₃, tBu), 35.1 (C, tBu), 36.3 (C, tBu), 36.4 (C, tBu),

40.3 (CH), 71.0 (CMe₂), 124–166 ppm (aromatic carbon atoms); elemen-

tal analysis calcd (%) for C₄₄H₅₈NO₃PS: C 74.23, H 8.21, N 1.97; found:

C 74.28, H 8.21, N 1.99.

À

(m, 1H; CH₂C=), 2.24 (m, 1H; CH₂C=), 5.43 (m, 1H; CH allyl trans

Ligand L8d: Yield: 808 mg (50%); ³¹P NMR (C₆D₆): d=143.1 ppm;

H NMR (C₆D₆): d=0.49 (s, 9H; CH₃Si), 0.59 (s, 9H; CH₃Si), 1.19 (s,

3H; CH₃), 1.53 (s, 3H; CH₃), 1.74 (m, 2H; CH₂), 2.04 (m, 2H; CH₂

CH), 2.21 (m, 2H; CH₂C=), 3.32 (m, 1H; CH), 7.0–8.0 ppm (m, 15H;

À

to N), 5.57 (m, 1H; CH O), 6.02 (m, 1H; CH allyl trans to P), 6.21 (m,

1

1H; CH allyl central), 6.8–8.0 ppm (m, 14H; CH=); ¹³C NMR (CD₂Cl₂,

233 K): d=28.1 (CH₃), 29.4 (CH₃), 30.2–32.5 (CH₃, tBu), 33.5 (CMe₂),

À

34.5 (C, tBu), 34.7 (C, tBu), 35.2 (C, tBu), 36.2 (CH₂C=), 36.4 (C, tBu),

13

À

CH=); C NMR (C₆D₆): d=À0.1 (CH₃Si), 0.1 (CH₃Si), 21.9 (CH₂),

45.5 (CH₂), 68.4 (m; CH O), 81.4 (m; CH allyl trans to N), 95.9 (m; CH

À

23.4 (CH₂C=), 26.3 (CH₂CH), 27.9 (CH₃), 30.2 (CH₃), 39.3 (CH), 69.9

trans to P), 112.3 (m; CH allyl central), 124–170 ppm (aromatic carbon

atoms). Product C (30%): ³¹P NMR (CD₂Cl₂, 233 K): d=143.1 ppm (s,

1P); ¹H NMR (CD₂Cl₂, 233 K): d=0.59 (s, 6H; CH₃), 0.84 (s, 6H; CH₃),

1.29 (s, 18H; CH₃, tBu), 1.33 (s, 18H; CH₃, tBu), 1.59 (s, 36H; CH₃, tBu),

1.64 (m, 2H; CH₂), 1.71 (s, 18H; CH₃, tBu), 1.81 (m, 2H; CH₂), 2.06 (m,

À

(CH₂O), 122–166 ppm (aromatic carbon atoms); elemental analysis

calcd (%) for C₄₄H₅₀NO₃PSSi₂: C 69.53, H 6.63, N 1.84; found: C 69.57,

H 6.66, N 1.86.

General procedure for the preparation of [PdACTHNUTRGNEUNG

(h³-allyl)(L)]BF₄complexes

26–35: The corresponding ligand (0.05 mmol) and the complex [{PdACTHNUTRGENUG(N m

À

2H; CH₂C=), 2.18 (m, 2H; CH₂C=), 5.32 (m, 1H; CH allyl), 5.52 (m,

À

Cl)(h³-1,3-allyl)}₂] (0.025 mmol) were dissolved in CD₂Cl₂(1.5 mL) at

room temperature under argon. AgBF₄(9.8 mg, 0.5 mmol) was added

after 30 min and the mixture was stirred for 30 min. The mixture was

then filtered over Celite under argon and the resulting solutions were an-

alyzed by NMR spectroscopy. After the NMR spectroscopic analysis, the

complexes were precipitated adding hexane as pale yellow solids.

À

2H; CH O), 5.59 (m, 1H; CH allyl), 6.19 (m, 1H; CH allyl central), 6.8–

8.0 ppm (m, 18H; CH=); ¹³C NMR (CD₂Cl₂, 233 K): d=28.2 (CH₃), 29.6

(CH₃), 30.2-32.5 (CH₃, tBu), 33.7 (CMe₂), 34.3 (C, tBu), 34.9 (C, tBu),

À

35.0 (C, tBu), 35.5 (C, tBu), 36.3 (CH₂C=), 36.9 (C, tBu), 45.3 (CH₂),

À

69.2 (m; CH O), 99.7 (br; CH allyl), 112.5 (m; CH allyl central), 124–

170 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

0.7C₅₆H₇₃BF₄NO₄PPd+0.3C₉₇H₁₃₃BF₄N₂O₈P₂Pd: C 65.79, H 7.36, N 0.87;

found: C 65.87, H 7.42, N 0.92.

Complex 26: Isomer A (90%): ³¹P NMR (CD₂Cl₂, 263 K): d=135.6 ppm

(s, 1P); ¹H NMR (CD₂Cl₂, 263 K): d=0.97 (s, 3H; CH₃), 1.05 (s, 3H;

CH₃), 1.21 (s, 9H; CH₃, tBu), 1.25 (s, 9H; CH₃, tBu), 1.42 (s, 9H; CH₃,

tBu), 1.59 (s, 9H; CH₃, tBu), 1.72 (m, 1H; CH₂), 1.84 (m, 1H; CH₂), 1.96

Complex 29: Isomer A (83%): ³¹P NMR (CD₂Cl₂, 273 K): d=138.1 ppm

1

À

(s, 1P); H NMR (C₆D₆, 273 K): d=0.22 (s, 9H; CH₃Si), 0.75 (s, 9H;

À

CH₃Si), 1.04 (s, 3H; CH₃), 1.18 (s, 3H; CH₃), 1.92 (m, 1H; CH₂), 2.21

(m, 1H; CH₂), 2.53 (m, 2H; CH₂C=), 4.97 (m, 1H; CH allyl trans to N),

À

(m, 1H; CH₂C=), 2.23 (m, 1H; CH₂C=), 5.14 (m, 1H; CH allyl trans

À

to N), 5.39 (m, 1H; CH O), 5.99 (m, 1H; CH allyl trans to P), 6.55 (m,

1H; CH allyl central), 6.7–8.0 ppm (m, 19H; CH=); ¹³C NMR (C₆D₆,

263 K): d=26.3 (CH₃), 29.8 (CH₃), 31.3 (CH₃, tBu), 31.5 (CH₃, tBu), 32.5

À

5.38 (m, 1H; CH O), 6.06 (m, 1H; CH allyl trans to P), 6.42 (m, 1H;

CH allyl central), 6.6–8.3 ppm (m, 25H; CH=); ¹³C NMR (C₆D₆, 273 K):

À

d=0.7 (CH₃Si), 1.0 (CH₃Si), 28.2 (CH₃), 32.9 (CMe₂), 35.2 (CH₂C=),

À

(C, tBu), 34.8 (CH₂C=), 35.6 (CMe₂), 42.5 (CH₂), 70.7 (br; CH O), 81.4

(m; CH allyl trans to N), 95.9 (m; CH trans to P), 112.5 (m; CH allyl cen-

tral), 125–164 ppm (aromatic carbon atoms). Isomer B (10%): ³¹P NMR

(CD₂Cl₂, 263 K): d=140.4 ppm (s, 1P); ¹H NMR (CD₂Cl₂, 263 K): d=

0.99 (s, 3H; CH₃), 1.03 (s, 3H; CH₃), 1.14 (s, 9H; CH₃, tBu), 1.17 (s, 9H;

CH₃, tBu), 1.40 (s, 9H; CH₃, tBu), 1.55 (s, 9H; CH₃, tBu), 1.85 (m, 1H;

À

42.5 (d, J

C

G

CH allyl trans to N), 96.7 (m; CH allyl trans to P), 112.4 (m; CH allyl

central), 121–165 ppm (aromatic carbon atoms). Isomer

B

(17%):

1

³¹P NMR (CD₂Cl₂, 273 K): d=140.5 ppm (s, 1P); H NMR (C₆D₆, 273 K):

À

d=0.56 (s, 9H; CH₃Si), 0.69 (s, 9H; CH₃Si), 1.04 (s, 3H; CH₃), 1.07 (s,

À

3H; CH₃), 1.70 (m, 1H; CH₂), 1.98 (m, 1H; CH₂), 2.21 (m, 2H; CH₂

CH₂), 1.92 (m, 1H; CH₂C=), 2.10 (m, 1H; CH₂C=), 4.84 (m, 1H; CH

À

C=), 5.19 (m, 1H; CH allyl trans to N), 5.32 (m, 1H; CH allyl trans to P),

allyl trans to N), 5.34 (m, 1H; CH O), 5.21 (m, 1H; CH allyl trans to P),

6.45 (m, 1H; CH allyl central), 6.7–8.0 ppm (m, 19H; CH=); ¹³C NMR

(C₆D₆, 263 K): d=26.8 (CH₃), 30.1 (CH₃), 31.4 (CH₃, tBu), 31.6 (CH₃,

À

5.42 (m, 1H; CH O), 6.49 (m, 1H; CH allyl central), 6.6–8.3 ppm (m,

13

À

25H; CH=); C NMR (C₆D₆, 273 K): d=1.2 (CH₃Si), 1.5 (CH₃Si),

À

26.3 (CH₃), 29.5 (CH₃), 33.4 (CMe₂), 35.0 (CH₂C=), 42.7 (d, JACHTUNGTRENNUNG

3.2 Hz; CH₂), 68.5 (d, JACHTUNTGRENNUNG

N), 96.1 (m; CH allyl trans to P), 110.7 (m; CH allyl central), 121–

165 ppm (aromatic carbon atoms); elemental analysis calcd (%) for

C₅₆H₅₇BF₄NO₄PPdSi₂: C 61.80, H 5.28, N 1.29; found: C 61.92, H 5.34, N

1.33.

tBu), 32.0 (C, tBu), 35.1 (CH₂C=), 35.8 (CMe₂), 42.3 (CH₂), 69.7 (br;

À

CH O), 75.0 (m; CH allyl trans to N), 95.4 (m; CH trans to P), 112.7 (m;

CH allyl central), 125–164 ppm (aromatic carbon atoms); elemental anal-

ysis calcd (%) for C₅₈H₆₉BF₄NO₄PPd: C 65.20, H 6.51, N 1.31; found: C

65.43, H 6.61, N 1.35.

Complex 27: Isomer A (56%): ³¹P NMR (CD₂Cl₂, 243 K): d=132.5 ppm

(s, 1P); ¹H NMR (CD₂Cl₂, 243 K): d=1.45 (s, 9H; CH₃, tBu), 1.49 (s,

9H; CH₃, tBu), 1.65 (s, 9H; CH₃, tBu), 1.69 (s, 9H; CH₃, tBu), 1.82 (m,

2H; CH₂), 2.03 (m, 2H; CH₂CH), 2.56 (m, 2H; CH₂C=), 3.43 (m, 1H;

CH), 4.56 (m, 1H; CH₂O), 4.93 (m, 1H; CH allyl trans to N), 4.98 (m,

Complex 30: Isomer A (28%): ³¹P NMR (CD₂Cl₂, 223 K): d=140.6 ppm

1

À

(s, 1P); H NMR (C₆D₆, 223 K): d=0.04 (s, 9H; CH₃Si), 0.65 (s, 9H;

À

CH₃Si), 0.98 (s, 3H; CH₃), 1.20 (s, 3H; CH₃), 1.64 (m, 1H; CH₂), 2.03

(m, 1H; CH₂), 2.54 (m, 2H; CH₂C=), 4.80 (m, 1H; CH allyl trans to N),

À

5.33 (m, 1H; CH O), 5.77 (m, 1H; CH allyl trans to P), 6.17 (m, 1H;

1H; CH₂O), 5.87 (m, 1H; CH allyl trans to P), 6.33 (m, 1H; CH allyl

CH allyl central), 6.4–8.4 ppm (m, 25H; CH=); ¹³C NMR (C₆D₆, 223 K):

central), 7.0–8.4 ppm (m, 19H; CH=); ¹³C NMR (CD₂Cl₂, 243 K): d=

À

d=À0.5 (CH₃Si), 1.1 (CH₃Si), 25.1 (CH₃), 30.2 (CH₃), 33.5 (CMe₂),

22.1 (CH₂), 24.2 (CH₂C=), 25.9 (CH₂CH), 31.8–32.9 (br; CH₃, tBu),

À

34.8 (CH₂C=), 42.6 (d, J

ACHTUNGTRNE(NUNG C,P)=10.2 Hz; CH₂), 69.3 (CH O), 71.1 (d, J-

35.0 (C, tBu), 35.8 (C, tBu), 39.3 (CH), 69.1 (CH₂O), 80.4 (m; CH allyl

AHCTUNGERTG(NNUN C,P)=8.0 Hz; CH allyl trans to N), 98.4 (m; CH allyl trans to P), 110.9

trans to N), 98.3 (m; CH trans to P), 112.1 (m; CH allyl central), 125–

165 ppm (aromatic carbon atoms). Isomer B (44%): ³¹P NMR (CD₂Cl₂,

243 K): d=136.9 ppm (s, 1P); ¹H NMR (CD₂Cl₂, 243 K): d=1.42 (s, 9H;

CH₃, tBu), 1.52 (s, 9H; CH₃, tBu), 1.72 (s, 18H; CH₃, tBu), 1.89 (m, 2H;

(m; CH allyl central), 120–165 ppm (aromatic carbon atoms). Isomer B

(72%): ³¹P NMR (CD₂Cl₂, 223 K): d=141.1 ppm (s, 1P); H NMR (C₆D₆,

1

À

223 K): d=0.25 (s, 9H; CH₃Si), 0.69 (s, 9H; CH₃Si), 1.07 (s, 3H; CH₃),

1.14 (s, 3H; CH₃), 1.67 (m, 1H; CH₂), 2.18 (m, 1H; CH₂), 2.62 (m, 2H;

CH₂C=), 4.74 (m, 1H; CH allyl trans to N), 5.30 (m, 1H; CH allyl trans

to P), 5.37 (m, 1H; CH O), 6.21 (m, 1H; CH allyl central), 6.4–8.4 ppm

(m, 25H; CH=); C NMR (C₆D₆, 223 K): d=0.3 (CH₃Si), 1.4 (CH₃Si),

25.2 (CH₃), 30.8 (CH₃), 33.5 (CMe₂), 34.8 (CH₂C=), 43.0 (d, J

À

CH₂), 2.12 (m, 2H; CH₂CH), 2.63 (m, 2H; CH₂C=), 3.49 (m, 1H;

À

CH), 4.53 (m, 1H; CH₂O), 4.88 (m, 1H; CH allyl trans to N), 5.13 (m,

À

1H; CH₂O), 5.45 (m, 1H; CH allyl trans to P), 6.28 (m, 1H; CH allyl

13

central), 7.0–8.4 ppm (m, 19H; CH=); ¹³C NMR (CD₂Cl₂, 243 K): d=

À

22.3 (CH₂), 24.5 (CH₂C=), 26.1 (CH₂CH), 31.8–32.9 (br; CH₃, tBu),

N

Chem. Eur. J. 2010, 16, 620 – 638

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

635

M. Diꢁguez, P. G. Andersson et al.

À

9.4 Hz; CH₂), 69.2 (CH O), 70.5 (d, J

(C,P)=9.6 Hz; CH allyl trans to

CH₃, tBu), 1.50 (s, 9H; CH₃, tBu), 1.78 (s, 9H; CH₃, tBu), 1.94 (m, 2H;

À

N), 93.0 (d, J(C,P)=36.8 Hz; CH allyl trans to P), 111.2 (m; CH allyl cen-

G

CH₂), 2.06 (m, 2H; CH₂CH), 2.22 (m, 2H; CH₂C=), 2.73 (m, 1H;

À

tral), 120–165 ppm (aromatic carbon atoms); elemental analysis calcd

(%) for C₅₆H₅₇BF₄NO₄PPdSi₂: C 61.80, H 5.28, N 1.29; found: C 61.91, H

5.37, N 1.34.

CH₂C=), 3.18 (m, 1H; CH allyl trans to N), 3.83 (m, 1H; CH allyl trans

À

to P), 4.05 (m, 1H; CH O), 4.89 (m, 1H; CH allyl central), 7.1–8.2 ppm

(m, 9H; CH=); ¹³C NMR (CD₂Cl₂, 253 K): d=18.0 (CH₃allyl), 18.3

Complex 31: Isomer A (46%): ³¹P NMR (CD₂Cl₂, 295 K): d=134.3 ppm

(s, 1P); ¹H NMR (CD₂Cl₂, 295 K): d=0.84 (m, 3H; CH₃allyl), 1.12 (m,

3H; CH₃allyl), 1.15 (s, 3H; CH₃), 1.29 (s, 3H; CH₃), 1.35 (s, 9H; CH₃,

tBu), 1.39–1.42 (s, 18H; CH₃, tBu), 1.59 (s, 9H; CH₃, tBu), 1.95 (m, 1H;

À

(CH₃allyl), 21.1 (CH₂), 23.8 (CH₂C=), 25.9 (CH₂CH), 26.7 (CH₃), 30.2

(CH₃), 31.4-32.2 (CH₃, tBu), 35.1–36.2 (C, tBu), 46.5 (CH), 66.8 (m; CH

allyl trans to N), 78.2 (CMe₂), 95.4 (m; CH trans to P), 115.7 (m; CH

allyl central), 125–170 ppm (aromatic carbon atoms); elemental analysis

calcd (%) for C₄₉H₆₇BF₄NO₃PPdS: C 60.40, H 6.93, N 1.44; found: C

60.37, H 6.90, N 1.43.

À

CH₂), 2.35 (m, 1H; CH₂), 2.69 (m, 1H; CH₂C=), 2.73 (m, 1H; CH₂

C=), 4.12 (m, 1H; CH allyl trans to N), 5.03 (m, 1H; CH allyl trans to P),

5.36 (m, 1H; CH allyl central), 5.46 (m, 1H; CH O), 7.1–8.1 ppm (m,

Complex 33: Isomer A (45%): ³¹P NMR (CD₂Cl₂, 253 K): d=132.2 ppm

(s, 1P); H NMR (CD₂Cl₂, 253 K): d=0.42 (m, 9H; CH₃Si), 0.60 (m,

9H; CH₃Si), 0.68 (m, 3H; CH₃allyl), 0.87 (m, 3H; CH₃allyl), 1.21 (s,

3H; CH₃), 1.28 (s, 3H; CH₃), 1.84 (m, 2H; CH₂), 2.11 (m, 2H; CH₂

À

9H; CH=); ¹³C NMR (CD₂Cl₂, 295 K): d=16.3 (CH₃allyl), 19.4 (CH₃

allyl), 26.8 (CH₃), 29.9 (CH₃), 31.4–32.1 (CH₃, tBu), 32.5–33.6 (C, tBu),

1

À

35.2 (CH₂C=), 36.0 (CMe₂), 42.9 (br; CH₂), 70.6 (br; CH O), 72.3 (m;

CH allyl trans to N), 107.3 (m; CH trans to P), 115.3 (m; CH allyl cen-

tral), 123–164 ppm (aromatic carbon atoms). Isomer B (18%): ³¹P NMR

(CD₂Cl₂, 295 K): d=135.2 ppm (s, 1P); ¹H NMR (CD₂Cl₂, 295 K): d=

0.90 (m, 3H; CH₃allyl), 1.05 (m, 3H; CH₃allyl), 1.18 (s, 3H; CH₃), 1.28

(s, 3H; CH₃), 1.39–1.42 (s, 18H; CH₃, tBu), 1.49 (s, 9H; CH₃, tBu), 1.53

(s, 9H; CH₃, tBu), 1.98 (m, 1H; CH₂), 2.22 (m, 1H; CH₂), 2.73 (m, 1H;

À

CH), 2.24 (m, 2H; CH₂C=), 2.69 (m, 1H; CH₂C=), 3.89 (m, 1H; CH

À

allyl trans to N), 4.13 (m, 1H; CH O), 4.26 (m, 1H; CH allyl trans to P),

4.98 (m, 1H; CH allyl central), 7.0–8.4 ppm (m, 15H; CH=); ¹³C NMR

À

(CD₂Cl₂, 253 K): d=0.8 (CH₃Si), 1.4 (CH₃Si), 16.5 (CH₃allyl), 19.4

À

(CH₃allyl), 21.5 (CH₂), 24.2 (CH₂C=), 26.3 (CH₂CH), 26.6 (CH₃), 29.9

(CH₃), 45.8 (CH), 73.1 (m; CH allyl trans to N), 76.4 (CMe₂), 104.3 (m;

CH trans to P), 115.3 (m; CH allyl central), 125–170 ppm (aromatic

À

CH₂C=), 2.78 (m, 1H; CH₂C=), 4.50 (m, 1H; CH allyl trans to N),

4.73 (m, 1H; CH allyl trans to P), 5.42 (m, 1H; CH allyl central), 5.52

carbon atoms). Isomer B (5%): ³¹P NMR (CD₂Cl₂, 253 K): d=136.3 ppm

(m, 1H; CH O), 7.1–8.1 ppm (m, 9H; CH=); ¹³C NMR (CD₂Cl₂, 295 K):

d=16.2 (CH₃allyl), 17.5 (CH₃allyl), 27.3 (CH₃), 29.4 (CH₃), 31.4-32.1

(s, 1P); H NMR (CD₂Cl₂, 253 K): d=0.39 (m, 9H; CH₃Si), 0.57 (m,

9H; CH₃Si), 0.74 (m, 3H; CH₃allyl), 1.04 (m, 3H; CH₃allyl), 1.24 (s,

3H; CH₃), 1.31 (s, 3H; CH₃), 1.86 (m, 2H; CH₂), 2.11 (m, 2H; CH₂

CH), 2.24 (m, 2H; CH₂C=), 2.69 (m, 1H; CH₂C=), 3.90 (m, 1H; CH

1

À

(CH₃, tBu), 32.5-33.6 (C, tBu), 35.4 (CH₂C=), 36.3 (CMe₂), 42.9 (br;

À

CH₂), 70.2 (br; CH O), 74.5 (m; CH allyl trans to N), 106.3 (m; CH

À

trans to P), 116.8 (m; CH allyl central), 123–164 ppm (aromatic carbon

allyl trans to N), 4.10 (m, 1H; CH O), 4.15 (m, 1H; CH allyl trans to P),

atoms). Isomer D (36%): ³¹P NMR (CD₂Cl₂, 295 K): d=134.7 ppm (s,

4.95 (m, 1H; CH allyl central), 7.0–8.4 ppm (m, 15H; CH=); ¹³C NMR

1

À

1P); H NMR (CD₂Cl₂, 295 K): d=0.54 (m, 3H; CH₃allyl), 0.95 (m, 3H;

(CD₂Cl₂, 253 K): d=0.5 (CH₃Si), 1.2 (CH₃Si), 16.2 (CH₃allyl), 19.4

À

CH₃allyl), 1.20 (s, 3H; CH₃), 1.22 (s, 3H; CH₃), 1.39–1.42 (s, 9H; CH₃,

tBu), 1.45 (s, 9H; CH₃, tBu), 1.54 (s, 9H; CH₃, tBu), 1.60 (s, 9H; CH₃,

(CH₃allyl), 21.6 (CH₂), 24.1 (CH₂C=), 26.2 (CH₂CH), 26.7 (CH₃), 30.1

(CH₃), 45.6 (CH), 74.0 (m; CH allyl trans to N), 76.3 (CMe₂), 102.1 (m;

CH trans to P), 116.1 (m; CH allyl central), 125–170 ppm (aromatic

À

tBu), 1.98 (m, 1H; CH₂), 2.20 (m, 1H; CH₂), 2.78 (m, 1H; CH₂C=),

À

2.82 (m, 1H; CH₂C=), 3.61 (m, 1H; CH allyl trans to N), 3.87 (m, 1H;

carbon atoms). Isomer

D

(50%): ³¹P NMR (CD₂Cl₂, 253 K): d=

1

À

CH allyl trans to P), 5.23 (m, 1H; CH allyl central), 5.71 (m, 1H; CH

134.6 ppm (s, 1P); H NMR (CD₂Cl₂, 253 K): d=0.51 (m, 9H; CH₃Si),

0.58 (m, 9H; CH₃Si), 0.75 (m, 3H; CH₃allyl), 0.82 (m, 3H; CH₃allyl),

1.27 (s, 3H; CH₃), 1.41 (s, 3H; CH₃), 1.84 (m, 2H; CH₂), 2.11 (m, 2H;

O), 7.1–8.1 ppm (m, 9H; CH=); ¹³C NMR (CD₂Cl₂, 295 K): d=17.5 (CH₃

allyl), 18.8 (CH₃allyl), 27.5 (CH₃), 29.4 (CH₃), 31.4–32.1 (CH₃, tBu),

À

32.5–33.6 (C, tBu), 35.5 (CH₂C=), 36.2 (CMe₂), 42.9 (br; CH₂), 69.8 (br;

CH₂CH), 2.24 (m, 2H; CH₂C=), 2.69 (m, 1H; CH₂C=), 3.64 (m, 1H;

CH allyl trans to N), 3.98 (m, 1H; CH allyl trans to P), 4.18 (m, 1H;

À

CH O), 70.6 (m; CH allyl trans to N), 95.0 (m; CH trans to P), 118.6 (m;

À

CH allyl central), 123–164 ppm (aromatic carbon atoms); elemental anal-

ysis calcd (%) for C₄₈H₆₅BF₄NO₄PPd: C 61.06, H 6.94, N 1.48; found: C

61.11, H 6.96, N 1.49.

Complex 32: Isomer A (40%): ³¹P NMR (CD₂Cl₂, 253 K): d=127.4 ppm

(s, 1P); ¹H NMR (CD₂Cl₂, 253 K): d=0.63 (m, 3H; CH₃allyl), 0.85 (m,

3H; CH₃allyl), 1.19 (s, 3H; CH₃), 1.26 (s, 3H; CH₃), 1.37 (s, 9H; CH₃,

tBu), 1.39 (s, 9H; CH₃, tBu), 1.44 (s, 9H; CH₃, tBu), 1.51 (s, 9H; CH₃,

CH O), 4.79 (m, 1H; CH allyl central), 7.0–8.4 ppm (m, 15H; CH=);

13

À

C NMR (CD₂Cl₂, 253 K): d=0.9 (CH₃Si), 1.0 (CH₃Si), 16.4 (CH₃

À

allyl), 19.2 (CH₃allyl), 21.7 (CH₂), 24.0 (CH₂C=), 26.1 (CH₂CH), 26.9

(CH₃), 30.2 (CH₃), 45.9 (CH), 71.3 (m; CH allyl trans to N), 76.3 (CMe₂),

96.1 (m; CH trans to P), 115.5 (m; CH allyl central), 125–170 ppm (aro-

matic

carbon

atoms);

elemental

analysis

calcd

(%)

for

C₄₇H₅₅BF₄NO₃PPdSSi₂: C 56.77, H 5.58, N 1.41; found: C 56.73, H 5.55,

N 1.38.

Complex 34: Isomer A (15%): ³¹P NMR (CD₂Cl₂): d=139.1 ppm (s, 1P);

H NMR (CD₂Cl₂): d=0.32 (s, 9H; CH₃Si), 0.44 (s, 9H; CH₃Si), 1.09

(s, 3H; CH₃), 1.16 (m, 3H; CH₃), 1.39 (m, 2H; CH₂, allyl), 1.49 (m, 2H;

À

tBu), 1.85 (m, 2H; CH₂), 2.06 (m, 2H; CH₂CH), 2.22 (m, 2H; CH₂

C=), 2.73 (m, 1H; CH₂C=), 3.42 (m, 1H; CH allyl trans to N), 4.26 (m,

À

1

À

1H; CH O), 4.56 (m, 1H; CH allyl trans to P), 4.91 (m, 1H; CH allyl

central), 7.1–8.2 ppm (m, 9H; CH=); ¹³C NMR (CD₂Cl₂, 253 K): d=17.0

À

(CH₃allyl), 18.1 (CH₃allyl), 21.0 (CH₂), 23.8 (CH₂C=), 26.0 (CH₂CH),

26.1 (CH₃), 29.5 (CH₃), 31.4–32.2 (CH₃, tBu), 35.1–36.2 (C, tBu), 46.5

CH₂), 1.72 (m, 4H; CH₂allyl), 1.92 (m, 1H; CH₂CH), 2.14 (m, 1H;

À

CH₂CH), 2.72 (CH₂C=), 4.94 (m, 1H; CH allyl trans to N), 5.49 (m,

À

(CH), 64.8 (m; CH allyl trans to N), 78.3

(CMe₂), 107.8 (m; CH trans to

1H; CH O), 5.79 (m, 1H; CH allyl central), 5.98 (m, 1H; CH allyl trans

to P), 6.8–8.4 ppm (m, 15H; CH=); C NMR (CD₂Cl₂): d=0.3 (CH₃Si),

19.1 (CH₂allyl), 26.3 (CH₂allyl), 28.2 (CH₃), 28.7 (CH₃), 31.0 (CH₂

allyl), 33.0 (CMe₂), 35.5 (CH₂C=), 42.2 (m; CH₂), 69.7 (CH O), 70.6

(m; CH allyl trans to N), 103.2 (d, J(C,P)=38.2 Hz; CH allyl trans to P),

13

À

P), 115.8 (m; CH allyl central), 125–170 ppm (aromatic carbon atoms).

Isomer

B

(8%): ³¹P NMR (CD₂Cl₂, 253 K): d=129.1 ppm (s, 1P);

¹H NMR (CD₂Cl₂, 253 K): d=0.53 (m, 3H; CH₃allyl), 0.74 (m, 3H; CH₃

allyl), 1.15 (s, 3H; CH₃), 1.31 (s, 3H; CH₃), 1.32 (s, 9H; CH₃, tBu), 1.53

(s, 9H; CH₃, tBu), 1.62 (s, 9H; CH₃, tBu), 1.71 (s, 9H; CH₃, tBu), 1.87

À

AHCTUNGTRENNUNG

112.7 (m; CH allyl central), 121–167 ppm (aromatic carbon atoms).

Isomer B (85%): ³¹P NMR (CD₂Cl₂): d=138.7 ppm (s, 1P); ¹H NMR

À

(m, 2H; CH₂), 2.06 (m, 2H; CH₂CH), 2.22 (m, 2H; CH₂C=), 2.73 (m,

1H; CH₂C=), 3.48 (m, 1H; CH allyl trans to N), 3.71 (m, 1H; CH allyl

À

(CD₂Cl₂): d=0.37 (s, 9H; CH₃Si), 0.52 (s, 9H; CH₃Si), 0.94 (m, 2H;

CH₂, allyl), 1.14 (s, 3H; CH₃), 1.23 (s, 3H; CH₃), 1.42 (m, 4H; CH₂and

CH₂allyl), 1.62 (m, 2H; CH₂allyl), 2.03 (m, 1H; CH₂CH), 2.26 (m,

1H; CH₂CH), 2.75 (CH₂C=), 3.72 (m, 1H; CH allyl trans to N), 5.30

À

trans to P), 4.11 (m, 1H; CH O), 5.07 (m, 1H; CH allyl central), 7.1–

8.2 ppm (m, 9H; CH=); ¹³C NMR (CD₂Cl₂, 253 K): d=17.2 (CH₃allyl),

À

18.6 (CH₃allyl), 20.7 (CH₂), 23.8 (CH₂C=), 25.7 (CH₂CH), 26.8 (CH₃),

29.1 (CH₃), 31.4–32.2 (CH₃, tBu), 35.1–36.2 (C, tBu), 46.7 (CH), 65.7 (m;

CH allyl trans to N), 78.1 (CMe₂), 106.7 (m; CH trans to P), 115.9 (m;

(m, 1H; CH allyl central), 5.42 (m, 1H; CH allyl trans to P), 5.52 (m,

1H; CH O), 6.8–8.4 ppm (m, 15H; CH=); ¹³C NMR (CD₂Cl₂): d=0.9

À

CH allyl central), 125–170 ppm (aromatic carbon atoms). Isomer

D

(CH₃Si), 1.1 (CH₃Si), 20.2 (CH₂allyl), 25.5 (CH₂allyl), 26.5 (CH₃),

29.1 (CH₃), 30.9 (CH₂allyl), 33.6 (CMe₂), 35.5 (CH₂C=), 43.7 (CH₂),

69.9 (m; CH O), 70.4 (m; CH allyl trans to N), 106.2 (d, J

38.2 Hz; CH allyl trans to P), 111.3 (m; CH allyl central), 121–167 ppm

(52%): ³¹P NMR (CD₂Cl₂, 253 K): d=128.0 ppm (s, 1P); ¹H NMR

(CD₂Cl₂, 253 K): d=0.59 (m, 3H; CH₃allyl), 0.88 (m, 3H; CH₃allyl),

1.09 (s, 3H; CH₃), 1.21 (s, 3H; CH₃), 1.35 (s, 9H; CH₃, tBu), 1.46 (s, 9H;

À

N

636

www.chemeurj.org

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2010, 16, 620 – 638

A Modular P,N-Ligand Library

FULL PAPER

(aromatic carbon atoms); elemental analysis calcd (%) for

C₄₇H₅₃BF₄NO₄PPdSi₂: C 57.82, H 5.47, N 1.43; found: C 57.91, H 5.51, N

1.45.

fore).^[15b]For substrates S7 and S8, to determine the ee by HPLC (Chiral-

cel OJ, 13% 2-propanol/hexane, flow 0.5 mLmin^À1), a sample was filtered

over basic alumina using dichloromethane as the eluent.^[24]For substrates

S9 and S10, to determine the ee by HPLC (Chiralcel OJ, 13% 2-propa-

nol/hexane, flow 0.7 mLmin^À1), a sample was filtered over basic alumina

using dichloromethane as the eluent.^[39]

Complex 35: Isomer A (87%): ³¹P NMR (CD₂Cl₂): d=141.6 ppm (s, 1P);

1

À

H NMR (CD₂Cl₂): d=0.53 (s, 9H; CH₃Si), 0.56 (s, 9H; CH₃Si), 0.89

(m, 2H; CH₂, allyl), 1.15 (s, 3H; CH₃), 1.21 (m, 2H; CH₂, allyl), 1.32 (s,

3H; CH₃), 1.36 (m, 2H; CH₂), 1.45 (m, 2H; CH₂allyl), 1.96 (m, 1H;

Typical procedure of allylic amination of disubstituted linear substrate

3

À

S1: A degassed solution of [{PdCl

N

CH₂CH), 2.17 (m, 1H; CH₂CH), 2.72 (CH₂C=), 3.87 (m, 1H; CH

À

the corresponding phosphite–nitrogen ligand (0.0055 mmol) in dichloro-

methane (0.5 mL) was stirred for 30 min. Subsequently, a solution of the

corresponding substrate (0.5 mmol) in dichloromethane (1.5 mL) and

benzylamine (131 mL, 1.5 mmol) were added. The reaction mixture was

stirred at room temperature. After the desired reaction time, the reaction

mixture was diluted with Et₂O (5 mL) and saturated NH₄Cl (aq) (25 mL)

was added. The mixture was extracted with Et₂O (3ꢄ10 mL) and the ex-

tract dried over MgSO₄. Solvent was removed and conversion was mea-

allyl trans to N), 5.21 (m, 1H; CH allyl central), 5.32 (m, 1H; CH O),

5.36 (m, 1H; CH allyl trans to P), 6.8–8.4 ppm (m, 15H; CH=); ¹³C NMR

À

(CD₂Cl₂): d=0.9 (CH₃Si), 1.1 (CH₃Si), 20.2 (CH₂allyl), 25.5 (CH₂

À

allyl), 26.5 (CH₃), 29.1 (CH₃), 30.9 (CH₂allyl), 33.6 (CMe₂), 35.5 (CH₂

À

C=), 43.7 (CH₂), 68.6 (m; CH allyl trans to N), 69.9 (m; CH O), 107.6

(d, J

121–167 ppm (aromatic carbon atoms). Isomer

(CD₂Cl₂): d=140.3 ppm (s, 1P); ¹H NMR (CD₂Cl₂): d=0.54 (s, 9H;

(C,P)=38.2 Hz; CH allyl trans to P), 111.3 (m; CH allyl central),

B

(13%): ³¹P NMR

1

sured by H NMR spectroscopy. To determine the ee by HPLC (Chiralcel

À

CH₃Si), 0.59 (s, 9H; CH₃Si), 1.16 (s, 3H; CH₃), 1.24 (m, 4H; CH₃and

OJ, 13% 2-propanol/hexane, flow 0.5 mLmin^À1), a sample was filtered

over silica using 10% Et₂O/hexane mixture as the eluent.^[38]

À

CH₂allyl), 1.49 (m, 1H; CH₂allyl), 1.67 (m, 1H; CH₂CH), 1.93 (m,

À

1H; CH₂allyl), 2.08 (m, 1H; CH₂CH), 2.72 (CH₂C=), 4.69 (m, 1H;

CH allyl trans to N), 4.84 (m, 1H; CH O), 5.18 (m, 1H; CH allyl trans

to P), 5.41 (m, 1H; CH allyl central), 6.8–8.4 ppm (m, 15H; CH=);

C NMR (CD₂Cl₂): d=1.2 (CH₃Si), 1.6 (CH₃Si), 20.2 (CH₂allyl), 25.5

À

13

À

Acknowledgements

(CH₂allyl), 26.6 (CH₃), 29.2 (CH₃), 30.8 (CH₂allyl), 33.4 (CMe₂), 35.5

À

(CH₂C=), 45.6 (CH₂), 62.4 (m; CH O), 68.6 (m; CH allyl trans to N),

104.7 (d, J(C,P)=34.6 Hz; CH allyl trans to P), 112.4 (m; CH allyl cen-

We thank the Spanish Government (Consolider-Ingenio CSD2006-0003,

CTQ2007-62288/BQU, 2008PGIR/07 to O.P., and 2008PGIR/08 to M.D.),

the Catalan Government (2005SGR007777), COST D40, Vetenskapsrꢅ-

det (VR), and Astra Zeneca for their support.

ACHTUNGTRENNUNG

tral), 121–167 ppm (aromatic carbon atoms); elemental analysis calcd

(%) for C₄₇H₅₃BF₄NO₄PPdSi₂: C 57.82, H 5.47, N 1.43; found: C 57.87, H

5.49, N 1.44.

Study of the reactivity of the [Pd

ACHTUNGTRENNUNG

by in situ NMR spectroscopy:^[37]A solution of in situ prepared [Pd

AHCTUNGTRENNUNG

[1] For reviews, see: a) J. Tsuji, Palladium Reagents and Catalysis, Inno-

vations in Organic Synthesis, Wiley, New York, 1995; b) B. M. Trost,

D. L. van Vranken, Chem. Rev. 1996 , 96 , 395; c) M. Johannsen,

K. A. Jorgensen, Chem. Rev. 1998 , 98 , 1689; d) A. ltz, M. Lautens in

Comprehensive Asymmetric Catalysis, Vol. 2 (Eds.: E. N. Jacobsen,

A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, Chapter 24; e) G.

Helmchen, A. Pfaltz, Acc. Chem. Res. 2000 , 33 , 336; f) A. M.

Masdeu-Bultꢆ, M. Diꢁguez, E. Martꢂn, M. Gꢆmez, Coord. Chem.

Rev. 2003, 242, 159; g) B. M. Trost, M. L. Crawley, Chem. Rev. 2003 ,

103 , 2921; h) E. Martꢂn, M. Diꢁguez, C. R. Chim. 2007, 10, 188; i) Z.

Lu, S. Ma, Angew. Chem. 2008 , 120 , 264; Angew. Chem. Int. Ed.

2008 , 47 , 258.

[2] a) T. Hayashi, A. Yamamoto, T. Hagihara, Y. Ito, Tetrahedron Lett.

1986 , 27 , 191; b) T. Hayashi, Pure Appl. Chem. 1988 , 60 , 7; c) Re-

cently this concept has also been used to explain the chiral induction

by the Trost ligand, see: C. P. Butts, E. Filali, G. C. Lloyd-Jones,

P. O. Norrby, D. A. Sale, Y. Schramm, J. Am. Chem. Soc. 2009 , 131 ,

9945.

[3] See, for example: a) B. M. Trost, R. C. Bunt, J. Am. Chem. Soc.

1994 , 116 , 4089; b) B. M. Trost, A. C. Krueger, R. C. Bunt, J. Zam-

brano, J. Am. Chem. Soc. 1996 , 118 , 6520.

[4] See, for instance: a) G. J. Dawson, G. C. Frost, J. M. J. Williams, T e t-

rahedron Lett. 1993 , 34 , 3149; b) P. von Matt, A. Pfaltz, Angew.

Chem. 1993 , 105 , 614; Angew. Chem. Int. Ed. Engl. 1993 , 32 , 566;

c) P. Sennhenn, B. Gabler, G. Helmchen, Tetrahedron Lett. 1994 , 35 ,

8595.

[5] The flexibility that the biaryl moiety offers can be used to fine-tune

the chiral pocket formed upon complexation. See, for example:

a) O. Pꢀmies, M. Diꢁguez, C. Claver, J. Am. Chem. Soc. 2005, 127,

3646; b) Y. Mata, M. Diꢁguez, O. Pꢀmies, C. Claver, Adv. Synth.

Catal. 2005 , 347 , 1943.

[6] See, for instance: a) G. P. F. van Strijdonck, M. D. K. Boele, P. C. J.

Kamer, J. G. de Vries, P. W. N. M. van Leeuwen, Eur. J. Inorg.

Chem. 1999, 1073; b) M. Diꢁguez, O. Pꢀmies, C. Claver, Adv. Synth.

Catal. 2005, 347, 1257; c) M. Diꢁguez, O. Pꢀmies, C. Claver, J. Org.

Chem. 2005, 70, 3363; d) M. Diꢁguez, O. Pꢀmies, C. Claver, Adv.

Synth. Catal. 2007, 349, 836; e) O. Pꢀmies, M. Diꢁguez, Chem. Eur.

J. 2008, 14, 944; f) E. Raluy, O. Pꢀmies, M. Diꢁguez, J. Org. Chem.

2007 , 72 , 2842.

lyl)(L)]BF₄(L=phosphite–nitrogen ligand, 0.05 mmol) in CD₂Cl₂(1 mL)

was cooled in the NMR spectroscopy tube at À808C. At this tempera-

ture, a solution of cooled sodium malonate (0.1 mmol) was added. The

reaction was then followed by ³¹P NMR spectroscopy. The relative reac-

tion rates were calculated using a capillary containing a solution of tri-

phenylphosphine in CD₂Cl₂as external standard.

Typical procedure of allylic alkylation of disubstituted linear (S1 and S3)

3

À

and cyclic (S4–S6) substrates: A degassed solution of [PdCl

N

(0.9 mg, 0.0025 mmol) and the corresponding phosphite–nitrogen ligand

(0.0055 mmol) in dichloromethane (0.5 mL) was stirred for 30 min. Sub-

sequently, a solution of the corresponding substrate (0.5 mmol) in di-

chloromethane (1.5 mL), dimethyl malonate (171 mL, 1.5 mmol), N,O-

bis(trimethylsilyl)acetamide (370 mL, 1.5 mmol), and the corresponding

base (5 mg) were added. The reaction mixture was stirred at room tem-

perature. After the desired reaction time, the reaction mixture was dilut-

ed with Et₂O (5 mL) and saturated aqueous NH₄Cl (25 mL) was added.

The mixture was extracted with Et₂O (3ꢄ10 mL) and the extract dried

over MgSO₄. For substrate S1, solvent was removed and conversion was

1

measured by H NMR spectroscopy. To determine the ee by HPLC (Chir-

alcel OD, 0.5% 2-propanol/hexane, flow 0.5 mLmin^À1), a sample was fil-

tered over basic alumina using dichloromethane as the eluent.^[38]For sub-

strates S3–S6, conversion and enantiomeric excess were determined by

GC.^[24]

Typical procedure of allylic alkylation of disubstituted linear (S2), 1,3,3-

trisubstituted (S7 and S8), and monosubstituted (S9 and S10) substrates:

3

À

A degassed solution of [{PdCl

N

corresponding phosphite–nitrogen ligand (0.011 mmol) in dichlorome-

thane (0.5 mL) was stirred for 30 min at room temperature. Subsequently,

a solution of substrate (0.5 mmol) in dichloromethane (1.5 mL), dimethyl

malonate (171 mL, 1.5 mmol), N,O-bis(trimethylsilyl)acetamide (370 mL,

1.5 mmol), and KOAc (5 mg) were added. After 2 h at room tempera-

ture, the reaction mixture was diluted with Et₂O (5 mL) and saturated

aqueous NH₄Cl (25 mL) was added. The mixture was extracted with

Et₂O (3ꢄ10 mL) and the extract dried over MgSO₄. Solvent was re-

moved and conversion and regioselectivity were measured by ¹H NMR

spectroscopy. For substrate S2, enantiomeric excess was determined by

¹H NMR spectroscopy using [Eu

6,6,7,7,8,8,8-heptafluoro-2,2’-dimethyl-1,3,5- hydroxymethylene(+) can-

ACHTUNGERTN(NUNG hfc)₃] as resolving agent (hfc=

Chem. Eur. J. 2010, 16, 620 – 638

ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

637

M. Diꢁguez, P. G. Andersson et al.

[7] R. Prꢁtꢇt, A. Pfaltz, Angew. Chem. 1998, 110, 337; Angew. Chem.

Int. Ed. 1998, 37, 323.

[8] The choice of the oxazole and thiazole nitrogen donor units is based

on the fact that they resemble the successful oxazoline unit but are

much more robust.

[9] a) K. Kallstrom, C. Hedberg, P. Brandt, A. Bayer, P. G. Andersson,

J. Am. Chem. Soc. 2004, 126, 14308; b) C. Hedberg, K. Kallstrom, P.

Brandt, L. K. Hansen, P. G. Andersson, J. Am. Chem. Soc. 2006 ,

128 , 2995.

[10] O. Pꢀmies, M. Diꢁguez, G. Net, A. Ruiz, C. Claver, Organometallics

2000, 19, 1488.

[11] Similar behavior has been observed for other phosphite–nitrogen li-

gands. See, for example: a) reference [4b]; b) M. Diꢁguez, O.

Pꢀmies, Chem. Eur. J. 2008, 14, 3653.

[12] For more successful applications, see: a) P. Dierkes, S. Randechul, L.

Barloy, A. De Cian, J. Fischer, P. C. J. Kamer, P. W. N. M. van Leeu-

wen, J. A. Osborn, Angew. Chem. 1998 , 110 , 3299; Angew. Chem.

Int. Ed. 1998 , 37 , 3116; b) B. Wiene, G. Helmchen, Tetrahedron Lett.

1998, 39, 5727.

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Chem. 1997 , 69 , 513.

[14] See, for instance: a) A. Sudo, K. Saigo, J. Org. Chem. 1997 , 62 , 5508;

b) G. J. Dawson, J. M. J. Williams, S. J. Coote, Tetrahedro n : A symme-

try 1995 , 6 , 2535; c) C. J. Martin, D. J. Rawson, J. M. J. Williams, Tet-

rahedro n : A symmetry 1998 , 9 , 3723.

Aghmiz, M. Jimꢁnez-Pedrꢆs, A. M. Masdeu-Bultꢆ, M. Diꢁguez, C.

Claver, M. A. Maestro, Organometallics 2005, 24, 3946.

[19] The equilibrium between the two diastereoisomers takes place

through the so-called apparent p-allyl rotation. This has been shown

to occur through dissociation of one of the coordinated atoms of the

bidentate ligand, which allows the ligand to rotate. See: A. Gogoll,

J. ꢊrnebro, H. Grennberg, J. E. Bꢋckvall, J. Am. Chem. Soc. 1994 ,

116 , 3631.

[20] This study indicates that isomer 27A reacts around 1.3 times faster

than isomer 27B.

[21] This is also consistent with the fact that for both isomers the most

electrophilic allylic terminal carbon atom is the one trans to the

phosphite in the major isomer A.

[22] The formation of compound C was confirmed by adding an excess

of ligand, which resulted in an increase in the amount of species C

present in solution.

[23] A. M. Porte, J. Reibenspies, K. Burgess, J. Am. Chem. Soc. 1998 ,

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than isomer 34A.

[26] G. J. H. Buisman, P. C. J. Kamer, P. W. N. M. van Leeuwen, Tetrahe-

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[27] P. R. Auburn, P. B. Mackenzie, B. Bosnich, J. Am. Chem. Soc. 1985 ,

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Received: July 3, 2009

Published online: November 20, 2009

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Chem. Eur. J. 2010, 16, 620 – 638

Article Doi

A new class of modular P,N-ligand library for asymmetric Pd-catalyzed allylic substitution reactions: A study of the key Pd-π- allyl intermediates

DOI: 10.1002/chem.200901842

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