Palladium-catalyzed asymmetric phosphination. Enantioselective synthesis of PAMP-BH3, ligand effects on catalysis, and direct observation of the stereochemistry of transmetalation and reductive elimination

Organometallics 2003, 22, 3205-3221

3205

P a lla d iu m -Ca ta lyzed Asym m etr ic P h osp h in a tion .

En a n tioselective Syn th esis of P AMP -BH₃, Liga n d Effects

on Ca ta lysis, a n d Dir ect Obser va tion of th e

Ster eoch em istr y of Tr a n sm eta la tion a n d Red u ctive

Elim in a tion

J illian R. Moncarz, Tim J . Brunker, J ohn C. J ewett, Michael Orchowski, and

David S. Glueck*

6128 Burke Laboratory, Department of Chemistry, Dartmouth College,

Hanover, New Hampshire 03755

Roger D. Sommer, Kin-Chung Lam, Christopher D. Incarvito,

Thomas E. Concolino, Christopher Ceccarelli, Lev N. Zakharov, and

Arnold L. Rheingold

Department of Chemistry, University of Delaware, Newark, Delaware 19716

Received February 28, 2003

The complexes Pd(diphos)(o-An)(I) (o-An ) o-MeOC₆H₄; diphos ) dppe (3), (S,S)-Chiraphos

(4), (R,R)-Me-Duphos (5), (R,S)-t-Bu-J osiphos (6), (R)-Tol-Binap (7)) were prepared. Complex

6 catalyzed the coupling of PH(Me)(Ph)(BH₃) (2) with o-AnI in the presence of base to yield

PAMP-BH₃(P(Me)(Ph)(o-An)(BH₃) (1)) in low enantiomeric excess. The course of stoichio-

metric reactions of 3-7 with 2 and NaOSiMe₃depended on the diphosphine ligand.

Complexes 6 and 7 gave PAMP-BH₃(1) and Pd(0) species; no intermediates were observed.

With 3, the intermediate Pd(dppe)(o-An)(P(Me)(Ph)(BH₃)) (10) was observed by ³¹P NMR,

while 4 gave the isolable diastereomeric palladium complexes (S_P)-Pd((S,S)-Chiraphos)(o-

An)(P(Me)(Ph)(BH₃)) (11a ) and (R_P)-Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH₃)) (11b), whose

absolute configurations were determined by X-ray crystallography after separation. The

analogous Pd((R,R)-Me-Duphos)(o-An)(P(Me)(Ph)(BH₃)) diastereomers (12a ,b) were also

separated and isolated. Treatment of 4 with highly enantioenriched 2 (R or S) gave 11a or

11b in high diastereomeric excess with retention of configuration at phosphorus. P-C

reductive elimination from either isomer of highly diastereoenriched 11 in the presence of

excess diphenylacetylene yielded Pd((S,S)-Chiraphos)(PhCtCPh) (14) and highly enantioen-

riched PAMP-BH₃(1), with retention of configuration.

Ch a r t 1

In tr od u ction

The historical and industrial importance of the chiral

phosphine-borane P(Me)(Ph)(o-An)(BH₃) (PAMP-BH₃,

1; o-An ) o-MeOC₆H₄), a precursor to the useful

DiPAMP ligand¹(Chart 1), is reflected by the variety

of different syntheses reported.²Like most preparations

of enantiopure P-chirogenic phosphines, these all re-

quire a stoichiometric amount of chiral reagent.³

metal-catalyzed asymmetric synthesis would be an

A

attractive alternative, and some observations in the

literature suggested this approach would be possible.

P-chirogenic substrates containing the P(dO)(H) moi-

ety undergo palladium-catalyzed coupling with aryl or

(1) Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J .; Bachman, G.

L.; Weinkauff, D. J . J . Am. Chem. Soc. 1977, 99, 5946-5952.

(2) (a) Imamoto, T.; Kusumoto, T.; Suzuki, N.; Sato, K. J . Am. Chem.

Soc. 1985, 107, 5301-5303. (b) J uge, S.; Stephan, M.; Laffitte, J . A.;

Genet, J . P. Tetrahedron Lett. 1990, 31, 6357-6360. (c) Imamoto, T.;

Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J . Am. Chem. Soc.

1990, 112, 5244-5252. (d) Schmidt, U.; Riedl, B.; Griesser, H.; Fitz,

C. Synthesis 1991, 655-657. (e) Imamoto, T.; Oshiki, T.; Onozawa, T.;

Matsuo, M.; Hikosaka, T.; Yanagawa, M. Heteroat. Chem. 1992, 3,

563-575. (f) Corey, E. J .; Chen, Z.; Tanoury, G. J . J . Am. Chem. Soc.

1993, 115, 11000-11001. (g) Uziel, J .; Stephan, M.; Kaloun, E. B.;

Genet, J . P.; J uge, S. Bull. Soc. Chim. Fr. 1997, 134, 379-389. (h)

Vedejs, E.; Donde, Y. J . Am. Chem. Soc. 1997, 119, 9293-9294. (i)

Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T. J . Org. Chem. 2000,

65, 4776-4778.

(3) (a) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94,

1375-1411. (b) Kagan, H. B.; Sasaki, M. In The Chemistry of

Organophosphorus Compounds; Hartley, F. R., Ed.; Wiley: Chichester,

U.K., 1990; Vol. 1, pp 51-102. (c) This statement refers to asymmetric

synthesis, but biocatalytic resolution of racemic P-chirogenic phos-

phines, or their derivatives, yields chiral products using a catalytic

amount of chiral material (enzyme). For examples, see: Shioji, K.;

Tashiro, A.; Shibata, S.; Okuma, K. Tetrahedron Lett. 2003, 44, 1103-

1105. Shioji, K.; Ueno, Y.; Kurauchi, Y.; Okuma, K. Tetrahedron Lett.

2001, 42, 6569. Serreqi, A. N.; Kazlauskas, R. J . J . Org. Chem. 1994,

59, 7609-7615. Kielbasinski, P.; Zurawinski, R.; Pietrusiewicz, K. M.;

Zablocka, M.; Mikolajczyk, M. Tetrahedron Lett. 1994, 35, 7081-7084.

Publication on Web 06/27/2003

3206 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

Sch em e 1

vinyl halides or triflates with retention of configuration

at phosphorus.⁴With phosphine-boranes, however,

Imamoto observed that coupling of enantiopure PH(Me)-

(Ph)(BH₃) (2) with o-AnI to give 1 led to retention or

inversion of P stereochemistry, depending on base,

solvent, and temperature.⁵More recently, Livinghouse

showed that adding Cu(I) to similar reaction mixtures

gave tertiary phosphine-boranes in high enantiomeric

excess (ee) with retention of configuration at phos-

phorus.²ⁱP-C bond formation presumably occurs via

oxidative addition of o-AnI to Pd(0), replacement of the

iodide with (P(Me)(Ph)(BH₃))^-, and reductive elimina-

tion to yield the product and regenerate Pd(0); Brown

and Gaumont have directly observed these steps in

related cross-couplings.⁶

Both Imamoto and Livinghouse have reported that

loss of P stereochemistry is possible in the formation of

PAMP-BH₃from enantiopure 2, presumably because

the anion (P(Me)(Ph)(BH₃))^-, formed by deprotonation

of the secondary phosphine-borane, can racemize before

Pd-P bond formation.⁷If this racemization occurs more

quickly than Pd-P bond formation with a chiral Pd

catalyst, and if one enantiomer of the anion reacts more

quickly than the other with the intermediate Pd-

(diphos*)(o-An)(I) (diphos* ) chiral diphosphine), dy-

namic kinetic resolution⁸might afford enantioenriched

PAMP-BH₃via the mechanism of Scheme 1. Here we

report the successful development of a catalytic asym-

metric synthesis of PAMP-BH₃according to this scheme,

albeit in low enantiomeric excess (ee).⁹

metalation) and P-C bond formation (reductive elimi-

nation).¹⁰Both steps proceed with retention of configu-

ration at phosphorus, and the effect of reaction conditions

on transmetalation stereochemistry was observed di-

rectly.

These observations are significant because stereocon-

trol in such reactions has been ascribed to the trans-

metalation step, assuming that reductive elimination

proceeds with retention of configuration at phospho-

rus.^4,5However, these steps could not be separated and

observed directly. More generally, such fundamental

information on the stereochemistry of organometallic

reactions, while important in asymmetric catalysis, is

incompletely documented.¹¹For example, a standard

textbook states that “A great deal of evidence suggests

that the formation of C-C, C-H, and C-X bonds by

reductive elimination always proceeds with retention of

stereochemistry at carbon, although no case has been

reported in which an isolated starting material of known

stereochemistry has eliminated a product of known

stereochemistry.”¹²Recently, Hillhouse showed that

C-N bond formation at a Ni center led to inversion at

carbon, but in this oxidatively induced reductive elimi-

nation, the nature of the Ni(III) intermediate could not

be determined.¹³

Resu lts a n d Discu ssion

The catalyst precursors Pd(diphos*)(o-An)(I) (diphos*

) dppe (3), (S,S)-Chiraphos (4), (R,R)-Me-Duphos (5),

(R,S)-t-Bu-J osiphos (6), (R)-Tol-Binap (7)) were prepared

as shown in Scheme 2. The reaction between trans-Pd-

Testing a range of diphosphines as chiral auxiliaries

revealed important ligand effects on the individual steps

in the catalytic cycle and enabled direct observation of

the stereochemistry of Pd-P bond formation (trans-

(10) For a preliminary communication of some of these results, see:

Moncarz, J . R.; Brunker, T. J .; Glueck, D. S.; Sommer, R. D.; Rheingold,

A. L. J . Am. Chem. Soc. 2003, 125, 1180-1181.

(11) (a) For a review, see: Flood, T. C. In Topics in Stereochemistry;

Geoffroy, G. L., Ed.; Wiley: New York, 1981; Vol. 12, pp 37-117. For

recent studies of transmetalation to Pd, see: (b) Matos, K.; Soderquist,

J . A. J . Org. Chem. 1998, 63, 461-470. (c) Ridgway, B. H.; Woerpel,

K. A. J . Org. Chem. 1998, 63, 458-460. (d) Hatanaka, Y.; Hiyama, T.

J . Am. Chem. Soc. 1990, 112, 7793-7794. (e) Labadie, J . W.; Stille, J .

K. J . Am. Chem. Soc. 1983, 105, 669-670.

(12) (a) Collman, J . P.; Hegedus, L. S.; Norton, J . R.; Finke, R. G.

Principles and Applications of Organotransition Metal Chemistry;

University Science Books: Mill Valley, CA, 1987; p 333. (b) As

described in more detail in Flood’s review,^11aconclusions about the

stereochemistry of organometallic reaction steps are often based on

indirect evidence, such as the stereochemical results of a multistep

transformation, without observation, isolation, or knowledge of ster-

eochemistry of the intermediates.

(4) (a) Xu, Y.; Zhang, J . J . Chem. Soc., Chem. Commun. 1986, 1606

and references therein. (b) J ohansson, T.; Stawinski, J . Chem. Com-

mun. 2001, 2564-2565.

(5) (a) Reference 2e. (b) For analogous results with another second-

ary phosphine-borane, see: Oshiki, T.; Imamoto, T. J . Am. Chem. Soc.

1992, 114, 3975-3977.

(6) Gaumont, A.-C.; Hursthouse, M. B.; Coles, S. J .; Brown, J . M.

Chem. Commun. 1999, 63-64.

(7) For related studies, see: (a) Reference 5b. (b) Miura, T.; Yamada,

H.; Kikuchi, S.; Imamoto, T. J . Org. Chem. 2000, 65, 1877-1880. (c)

Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998, 120, 5116-5117.

(8) (a) Hoveyda, A. H.; Didiuk, M. T. Curr. Org. Chem. 1998, 2, 489-

526. (b) Ward, R. S. Tetrahedron: Asymmetry 1995, 6, 1475-1490. (c)

Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. J pn. 1995,

68, 36-56.

(9) During the course of this work, J ohn Brown (Oxford) informed

us that he had prepared enantioenriched chiral triarylphosphine-

boranes by a similar pathway using a Pd(Tol-Binap) catalyst: Gaumont,

A.-C.; Brown, J . M. Unpublished results, 1998.

(13) Lin, B. L.; Clough, C. R.; Hillhouse, G. L. J . Am. Chem. Soc.

2002, 124, 2890-2891.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3207

Sch em e 2

Sch em e 3^a

a

Heating the initially formed mixture gives a single isomer

of 6.

Ta ble 1. Selected NMR Da ta for th e Com p lexes

P d (d ip h os)(o-An )(I) (3-7)^a

compd δ (¹H)^bδ (¹³C)^b

a

Legend and conditions: diphos ) (S,S)-Chiraphos, (R,R)-

b

Me-Duphos, (R,S)-t-Bu-J osiphos, (R)-Tol-Binap. Legend and

conditions: diphos )dppe,Chiraphos.dppe )Ph₂PCH₂CH₂PPh₂.

See Scheme 3 for the structure of t-Bu-J osiphos.

diphos

δ (³¹P)

J _PP

dppe

3

3.22

3.14

3.35

3.72

3.74

3.46

3.20

g

54.5

d

56.1

53.7

53.2

g

51.9, 36.7 26

55.8, 42.4 37

57.1, 43.0 38

74.8, 69.0 24

73.8, 68.6 25

78.5, 15.9 37

70.2, 21.5 36

(S,S)-Chiraphos

(R,R)-Me-Duphos

(R,S)-t-Bu-J osiphos

(R)-Tol-Binap

4a ^c

4b

(PPh₃)₂(o-An)(I)¹⁴and dppe to yield 3 was rapid at room

temperature, but analogous reactions with more hin-

dered diphosphines were less convenient. For example,

using Chiraphos instead of dppe required 3 days and

gave 4 in only 48% yield. With (R)-Tol-Binap, no

reaction occurred at room temperature and a mixture

of products was obtained upon heating at 50 °C. Instead,

7 was synthesized following chemistry developed by

Hartwig¹⁵and Buchwald,¹⁶whereby Pd(dba)₂was treated

with P(o-Tol)₃and o-iodoanisole to give the sparingly

soluble dimer {Pd(P(o-Tol)₃)(o-An)(I)}₂(8). Subsequent

addition of (R)-Tol-Binap yielded 7 in moderate yields,

compromised by the formation of a purple impurity that

was removed upon recrystallization.

5a ^c

5b^c

6a ^e,c

6b^e

6c^f

6d ^f

7a ^c

7b

76.5, 4.7

81.8, 5.7

37

36

g

3.64

3.67

g

56.0

55.9

23.8, 12.3 37

23.4, 10.4 38

a

The solvent was CDCl₃for 3 (except ¹³C{¹H} NMR spectrum),

5, and 6, CD₂Cl₂for 4 and the ¹³C{¹H} NMR spectrum of 3, and

C₆D₆for 7. Chemical shifts are given in ppm, with coupling

constants in Hz. For 4-7, a (or c) refers to the major atropisomer

b

and

b

(or d ) to the minor one. OMe resonance. ^cRatio of

d

atropisomers: 4, 6:1; 5, 4.5:1; 6 (major isomer), 5:1; 7, 1.8:1. Not

observed. ^eIsolated isomer, PPh₂trans to I. ^fMinor isomer, solvent

g

THF, ratio of atropisomers not measured. Not measured.

In a more convenient synthesis, diphosphines readily

displaced TMEDA in Pd(TMEDA)(o-An)(I) (9)¹⁷to yield

complexes 3-7 as thermally robust, air-stable solids.

Reaction of 9 at room temperature in THF with (R,S)-

t-Bu-J osiphos was slow. After 24 h, the ³¹P{¹H} NMR

spectrum of the reaction mixture showed a 1:1 mixture

of regioisomers of 6, as well as some of the free ligand.

Heating to 50 °C promoted interconversion of the

isomers, one of which precipitated from THF (Scheme

3). The insolubility of this isomer drove the reaction to

completion, and 6 was isolated as a single isomer with

the PPh₂group trans to iodide, as established by X-ray

crystallography (see below). Once isolated, no further

isomerization occurred.

ranging from 24 to 38 Hz. The OMe group gave rise to

a sharp singlet (δ 3.1-3.9 in the ¹H NMR spectrum and

δ 53-57 in the ¹³C{¹H} NMR spectrum).

The NMR spectra of complexes 4-7 indicated the

presence of a second, minor atropisomer arising from

restricted rotation about the Pd-C bond, which was also

1

observed in the H NMR spectrum of 9. In that case,

rapid Pd-C(o-An) rotation on the NMR time scale would

make the two methyl groups on a given N equivalent,

because the aryl group passes through a molecular

plane of symmetry as it rotates. However, four sharp

NMe signals were observed, consistent with slow Pd-C

rotation on the NMR time scale. Similar behavior was

reported for Pd(TMEDA)(o-Tol)(Br)¹⁸and Pd(dppf)(o-

Tol)(NHNCPh₂)¹⁹(dppf ) Ph₂PC₅H₄FeC₅H₄PPh₂) and

in the closely related Pt(Diop)(o-An)(I) and Pt(Binap)-

(o-An)(Br).²⁰

Complexes 3-7 were characterized by NMR spectros-

copy (Table 1), by elemental analysis and, for 3-6, by

X-ray crystallography (see below). The ³¹P{¹H} NMR

spectra showed the expected AX patterns with J _PP

Barriers to Pd-C rotation were measured for com-

(14) Wallow, T. I.; Goodson, F. E.; Novak, B. M. Organometallics

1996, 15, 3708-3716.

1

plexes 4 and 7 by variable-temperature ³¹P{¹H} and H

(15) Paul, F.; Patt, J .; Hartwig, J . F. Organometallics 1995, 14,

3030-3039.

(18) Alsters, P. L.; Boersma, J .; Smeets, W. J . J .; Spek, A. L.; van

Koten, G. Organometallics 1993, 12, 1639-1647.

(19) Hartwig, J . F. Angew. Chem., Int. Ed. 1998, 37, 2090-2093.

(20) Diop ) O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphos-

phino)butane: Brown, J . M.; Perez-Torrente, J . J .; Alcock, N. W.

Organometallics 1995, 14, 1195-1203.

(16) (a) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996,

15, 2755-2763. (b) Wolfe, J . P.; Wagaw, S.; Buchwald, S. L. J . Am.

Chem. Soc. 1996, 118, 7215-7216.

(17) Kruis, D.; Markies, B. A.; Canty, A. J .; Boersma, J .; van Koten,

G. J . Organomet. Chem. 1997, 532, 235-242.

3208 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

Ta ble 2. Va r ia ble-Tem p er a tu r e NMR Da ta for th e

Atr op isom er ic P d Com p lexes P d (Dip h os*)(o-An )(I)

(4-7)^a

q

∆ν T_c

∆G_c

complex (diphos)

resonance δ (ppm) (Hz) (K) (kcal/mol)

4 ((S,S)-Chiraphos) ¹H (OMe) 3.25, 3.19 19 323

16.5

5 ((R,R)-Me-Duphos) ¹H (OMe) 3.67, 3.63 12 >368 >19.3^b

6 ((R,S)-t-Bu-

J osiphos)

7 ((R)-Tol-Binap)

¹H (Cp)

4.15, 4.00 43 >373 >18.6^c

¹H (Tol-Me) 2.10, 2.08

5 302

23.8, 23.4 47 318

16.3

15.6

³¹P

12.3, 10.4 227 >343 >15.9

a

Chemical shifts and ∆ν values from slow-exchange spectra

at 21 °C. Estimated errors are different for each resonance;

“typical” errors are 5 Hz in ∆ν, 10 °C in T_c, and 0.5 kcal/mol in

∆G_c^q. Solvents: C₆D₅Cl for 4 and 6, C₇D₈for 5, and C₆D₆for 7.

b

Consistent results were obtained from the ³¹P NMR spectrum,

where larger ∆ν values gave reduced lower bounds for the

rotational barrier. ^cConsistent results were obtained from the

OMe ¹H NMR signal and from the ³¹P NMR spectrum, where

larger ∆ν values gave reduced lower bounds for the rotational

barrier.

NMR spectroscopy; because coalescence was not ob-

served for 5 and 6, only lower bounds to the rotational

barriers could be established in those cases (Table 2).²¹

Summarizing related studies of atropisomerism in

square-planar Pd(II) and Pt(II) complexes of chiral

diphosphines, both Stang and Siehl²²and Brown²⁰noted

that diphosphines with a larger bite angle give rise to

higher rotation barriers. However, our results show that

bite angle is not the only factor affecting the rotational

barrier, since both the Duphos complex 5 (bite angle 87°)

and t-Bu-J osiphos complex 6 (bite angle 95.6°) had

rotational barriers higher than that of the (R)-Tol-Binap

complex 7 (the average Binap bite angle is 92.8°).²³

Presumably, the steric and electronic differences in the

groups on phosphorus also play a role in the energetics

of rotation.

F igu r e 1. ORTEP diagram of Pd(dppe)(o-An)(I) (3), with

thermal ellipsoids at the 30% probability level and hydro-

gen atoms omitted for clarity.

Cr ysta llogr a p h ic Stu d ies. The structures of com-

plexes 3-6 and 9 were determined by X-ray crystal-

lography. ORTEP diagrams are shown in Figures1-5,

data collection and structure refinement details are

summarized in Table 3, selected bond lengths and

angles for 3-6 are given in Table 4, and additional

information appears in the Experimental Section and

the Supporting Information. These complexes all adopt

a near-square-planar geometry at palladium, with the

aryl group oriented orthogonal to the square plane of

the molecule. The Me-Duphos and J osiphos complexes

5 and 6 show the greatest distortions from planarity,

as judged by the distances of ligand atoms from the P₂-

PdIC plane (up to 0.25 Å for P₁in 5 and 0.41 Å for I in

6). Despite steric and electronic differences between the

diphosphines, there was no significant difference in

Pd-C bond lengths. There was, however, a slight

difference in Pd-I bond lengths, with that in t-Bu-

J osiphos complex 6 being the longest. This result is

consistent with the greater steric congestion caused by

P(t-Bu)₂in comparison to PPh₂.

F igu r e 2. ORTEP diagram of Pd((S,S)-Chiraphos)(o-An)-

(I) (4), with thermal ellipsoids at the 30% probability level

and hydrogen atoms omitted for clarity.

Information),¹⁷and the previously reported Pd(TMEDA)-

(Ph)(I) (Table 5)²⁴suggest that methoxy substitution has

little steric or electronic effect on the structure of these

Pd aryl complexes.

Ca ta lysis. Complexes 3-7 were screened as catalyst

precursors for coupling of PH(Me)(Ph)(BH₃) and o-AnI

in the presence of base to make PAMP-BH₃. Many of

the bases tested (BuLi, NaOSiMe₃, i-Pr₂NEt, K₂CO₃,

Cs₂CO₃, KOH, pentamethylpiperidine) caused depro-

tection of the secondary phosphine-borane and/or the

Comparison of the crystal structures of Pd(TMEDA)-

(o-An)(I) (9), Pd(TMEDA)(p-An)(I) (see the Supporting

(21) Friebolin, H. Basic One- and Two-Dimensional NMR Spectros-

copy, 2nd ed.; VCH: Weinheim, Germany, 1993.

(22) Fuss, M.; Siehl, H.-U.; Olenyuk, B.; Stang, P. J . Organometallics

1999, 18, 758-769.

(23) Dierkes, P.; van Leeuwen, P. W. N. M. J . Chem. Soc., Dalton

Trans. 1999, 1519-1529.

(24) Markies, B. A.; Canty, A. J .; de Graaf, W.; Boersma, J .; J anssen,

M. D.; Hogerheide, M. P.; Smeets, W. J . J .; Spek, A. L.; van Koten, G.

J . Organomet. Chem. 1994, 482, 191-199.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3209

F igu r e 5. ORTEP diagram of Pd(TMEDA)(o-An)(I) (9),

with thermal ellipsoids at the 30% probability level and

hydrogen atoms omitted for clarity.

F igu r e 3. ORTEP diagram of Pd((R,R)-Me-Duphos)(o-An)-

(I)‚CH₂Cl₂(5‚CH₂Cl₂), with thermal ellipsoids at the 30%

probability level. Hydrogen atoms and the solvent molecule

are omitted for clarity.

NaOSiMe₃and stoichiometric Proton Sponge gave a

cleaner reaction with increased rate (ca. 8 turnovers per

day) without affecting the product ee.²⁵Details of the

catalysis are given in Table 6 and the Experimental

Section.

Stoichiometric versions of the catalytic reactions

provided more information on the reaction mechanism

and on the pronounced ligand effects on catalyst turn-

over (Scheme 5). Treatment of Pd((R,S)-t-Bu-J osiphos)-

(o-An)(I) (6) with 1 equiv of PH(Me)(Ph)(BH₃) (2) and

NaOSiMe₃in the presence of o-AnI led to the clean

formation of P(Me)(Ph)(o-An)(BH₃) (1); no intermediate

was observed. Although initially a single isomer of 6 was

used, oxidative addition of o-AnI to Pd(0) yielded a 5:1

mixture of isomers of 6. Similarly, treatment of Pd((R)-

Tol-Binap)(o-An)(I) (7) with 1 equiv of 2 and NaOSiMe₃

at room temperature in the presence of 1 equiv of (R)-

Tol-Binap gave P(Me)(Ph)(o-An)(BH₃) (1) and Pd((R)-

Tol-Binap)₂.²⁶When this reaction was carried out at -78

°C, the PAMP-BH₃product was observed by ³¹P NMR

even at -80 °C, and no intermediate could be identified.

In contrast, reaction of Pd(dppe)(o-An)(I) (3) with PH-

(Me)(Ph)(BH₃) and NaOSiMe₃in THF in the presence

of o-AnI gave the unstable (see below) intermediate Pd-

(dppe)(o-An)(P(Me)(Ph)(BH₃)) (10) as a 1:1 mixture of

atropisomers (Table 7). The related intermediates Pd-

(diphos*)(o-An)(P(Me)(Ph)(BH₃)) with Chiraphos and

Duphos ligands could be isolated. Treatment of Pd((S,S)-

Chiraphos)(o-An)(I) (4) and Pd((R,R)-Me-Duphos)(o-An)-

(I) (5) with PH(Me)(Ph)(BH₃) and NaOSiMe₃led to the

clean formation of a mixture of diastereomers 11a and

11b (the ratio depends on reaction conditions; see below)

and a 1:1 ratio of diastereomers 12a and 12b, respec-

tively (Scheme 5, Table 7). The phosphido-borane

complexes 10-12 show a characteristic broad ³¹P NMR

signal due to the P(Me)(Ph)(BH₃) group and J _PP(trans)

values of ca. 300 Hz, similar to related complexes

prepared by Gaumont and Brown.⁶

F igu r e 4. ORTEP diagram of Pd((R,S)-t-Bu-J osiphos)(o-

An)(I) (6), with thermal ellipsoids at the 30% probability

level and hydrogen atoms omitted for clarity.

tertiary phosphine-borane product or led to other

undesirable side reactions. Catalytic turnover was

observed only for tol-Binap and J osiphos complexes 6

and 7; since free tol-Binap and other decomposition

products were often observed during catalysis with 7,

the more robust J osiphos complex 6 was preferred.

Under optimized conditions (THF, 40 °C, Proton Sponge

as base; Scheme 4), PAMP-BH₃was formed in good

yield and isolated after workup by column chromatog-

raphy.

Unfortunately, the catalytic reaction was very slow

(ca. 5 turnovers per day), excess Proton Sponge was

required, and the enantiomeric excess (ee) of the prod-

uct, as determined by HPLC on a chiral column, was

low, 10% at best (the R enantiomer was favored). Using

the more kinetically active base NaOSiMe₃led to

formation of unidentified phosphine-borane byprod-

ucts, but the combination of a catalytic amount of

(25) Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Ferraris, D.;

Lectka, T. J . Am. Chem. Soc. 2002, 124, 6626-6635.

(26) Alcazar-Roman, L. M.; Hartwig, J . F.; Rheingold, A. L.; Liable-

Sands, L. M.; Guzei, I. A. J . Am. Chem. Soc. 2000, 122, 4618-4630.

3210 Organometallics, Vol. 22, No. 16, 2003

Ta ble 3. Cr ysta llogr a p h ic Da ta for Com p lexes 3-6, 9, 14, a n d 17

Moncarz et al.

3

4

5‚CH₂Cl₂

6

9

14

17

formula

fw

space group

a, Å

b, Å

c, Å

R, deg

â, deg

γ, deg

V, Å³

C

₃₃H₃₁IOP₂Pd C₃₅H₃₅IOP₂Pd C₂₆H₃₇Cl₂IOP₂Pd C₃₉H₄₇FeIOP₂Pd C₁₃H₂₃IN₂OPd C₄₂H₃₈P₂Pd

C₃₆H₅₆P₄Pd

719.09

P2₁

738.82

P1h

766.87

P2₁

9.0397(2)

14.2113(3)

12.5971(2)

90

729.68

P2₁2₁2₁

12.8392(2)

15.1191(2)

15.9153(2)

90

882.86

P2₁

9.7440(2)

11.9220(2)

15.9338(3)

90

456.63

P2₁/n

8.2681(2)

17.4132(2)

11.9951(2)

90

711.06

P2₁

9.9491(8)

22.4313(19) 18.1364(11)

16.2199(14) 19.6534(12)

90

9.836(2)

11.496(3)

14.168(3)

81.340(4)

80.800(4)

68.620(4)

1465.2(6)

2

10.5573(7)

90

101.237(2)

90

97.6465(10)

90

108.4800(8)

90

97.677(2)

90

103.7100(10)

90

3655.8(4)

4

1.306

0.706

1587.27(4)

2

3089.43(4)

4

1834.54(9)

2

1637.93(3)

4

3587.4(5)

4

Z

D(calcd), g/cm³

1.675

1.605

1.684

198(2)

1.569

1.893

173(2)

1.598

1.844

173(2)

1.852

3.010

173(2)

1.317

0.634

150(2)

µ(Mo KR), mm^-11.821

temp, K

173(2)

radiation

R(F), %^a

R_w(F²), %^a

Mo KR (0.71073 Å)

0.0529

0.1350

0.0714

0.2029

0.0420

0.1333

0.0384

0.0412

0.1225

0.0674

0.1437

0.0259

0.0649

0.1237

Quantity minimized ) R_w(F²) ) ∑[w(F_o- F_c²)²]/∑[(wF_o²)²]^1/2; R ) ∑∆/∑(F_o), ∆ ) |(F_o- F_c)|, w ) 1/[σ²(F_o²) + (aP)²+ bP], P ) [2F_c

a

2

+ Max(F_o,0)]/3.

Ta ble 4. Selected Bon d Len gth s (Å) a n d An gles

(d eg) in P d (d ip h os)(o-An )(I) Com p lexes 3-6

Sch em e 4

3

4

5‚CH₂Cl₂

6

diphos

dppe

2.078(5)

2.6668(9) 2.6201(19)

2.238(2)

2.359(2)

(S,S)-Chira- (R,R)-Me- (R,S)-t-Bu-

phos

2.067(9)

Duphos

2.083(6)

2.6675(6)

J osiphos

2.064(9)

2.7063(8)

Pd-C

Pd-I

Pd-P₁

Pd-P₂

C-Pd-I

P₁-Pd-P₂86.32(8)

P₁-Pd-C

P₂-Pd-I

2.209(5)

2.313(5)

2.2515(15) 2.245(2)

2.3184(16) 2.44(2)

87.15(17) 91.0(4)

91.74(17)

86.88(6)

88.51(17)

94.93(5)

82.4(2)

95.67(7)

84.4(2)

85.43(18)

85.60(18) 86.1(4)

100.21(6) 97.88(13)

102.56(5)

Ta ble 6. P d -Ca ta lyzed Asym m etr ic Syn th esis of

Ta ble 5. Selected Bon d Len gth s (Å) a n d An gles

(d eg) in P d (TMEDA)(Ar )(I) Com p lexes

a

P AMP -BH₃

method^bT (°C) time (days) conversn (%)^cyield (%)^d,eee (%)^f

1

2

25

40

25

40

10

5

7

88

95

89

80

76

68

65

10

2

7

3

9

a

For the general procedure, including workup details, see the

Experimental Section. rac-PH(Me)(Ph)(BH₃) (2) was treated with

o-AnI (2.1 equiv), a base (1.1 equiv), and complex 6 (4 mol %) in

THF, and the mixture was heated to 40 °C. Reactions were

Ar

b

monitored by ³¹P NMR spectroscopy. Method 1: base, Proton

a

o-MeOC₆H₄(9)

p-MeOC₆H₄

Ph^b

Sponge. Method 2: base, Proton Sponge (1.1 equiv) plus NaOSiMe₃

Pd-C

1.980(6)

2.5735(6)

88.79(17)

83.63(19)

2.125(5)

2.176(5)

92.0(2)

2.036(9)

2.5954(7)

89.7(2)

1.992(7)

2.5703(8)

87.4(2)

(0.04 equiv). ^cBy ³¹P NMR integration of 2 and PAMP-BH₃

Pd-I

d

signals. Based on amount of starting 2. ^eIsolated yields after

C-Pd-I

N-Pd-N

Pd-N₁

Pd-N₂

N₁-Pd-C

N₂-Pd-I

recrystallization from hexane/CH₂Cl₂. ^fDetermined by HPLC

(ChiralPak AD column) in comparison with racemic material.

84.2(2)

84.0(2)

2.156(7)

2.208(7)

91.1(3)

2.127(6)

2.193(6)

92.8(3)

12, recrystallization from THF/petroleum ether at -25

°C yielded a 2:1 mixture of diastereomers. However,

precipitation from THF at -25 °C yielded only 12a ,

according to ³¹P{¹H} NMR. A MeO signal due to a

second, minor isomer was observed in the ¹H NMR

spectrum (δ 3.63, CD₂Cl₂, major to minor ratio 16:1),

but it was unclear whether this was the other diaste-

reomer or an atropisomer, since a corresponding signal

was not observed in the ³¹P{¹H} NMR spectrum.

The Chiraphos and Me-Duphos complexes were fur-

ther characterized by ¹H and ¹³C NMR spectroscopy

(Table 8). These techniques, as well as ³¹P NMR spectra,

showed that minor atropisomers of 11 and 12 are

95.56(13)

95.00(17)

95.8(2)

a

Kruis, D.; Markies, B. A.; Canty, A. J .; Boersma, J .; van Koten,

G. J . Organomet. Chem. 1997, 532, 235-242. For details of the

crystal structure determination, see the Supporting Information.

Markies, B. A.; Canty, A. J .; de Graaf, W.; Boersma, J .; J anssen,

M. D.; Hogerheide, M. P.; Smeets, W. J . J .; Spek, A. L.; van Koten,

b

G. J . Organomet. Chem. 1994, 482, 191-199.

Because of their differing solubilities in ether, Chira-

phos complexes 11a and 11b could be separated and

isolated as single diastereomers or as samples highly

enriched in one diastereomer. For the Duphos complex

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3211

Ta ble 8. Selected ¹H NMR Da ta for

P d (d ip h os)(o-An )(P (Me)(P h )(BH₃)) Com p lexes

11a ,b a n d 12a ,b^{a -c}

Sch em e 5

δ(¹H)

diphos

compd

OMe

PMe

J _PH

(S,S)-Chiraphos

(R,R)-Me-Duphos

11a

3.23

3.11

3.41

3.29

3.59

3.66

0.44

0.59

0.44

0.67

0.85

0.79

9, 3

8, 3

8, 4

9, 3

e

11b

11c^d

11d ^d

12a

Ta ble 7. ³¹P {¹H} NMR Da ta for

P d (d ip h os)(o-An )(P (Me)(P h )(BH₃)) Com p lexes

10-12^a

12b^f

a

b

Chemical shifts in ppm and coupling constants in Hz. Sol-

vent: CD₂Cl₂for 11a and 12a ; THF-d₈for 11b-d ; acetone-d₆for

12b. ^cTemperature 21 °C. 11c is an atropisomer of 11b; 11d is

d

an atropisomer of 11a . ^eObscured due to peak overlap. ^fCom-

plexes 12 were not obtained analytically pure; therefore, ¹H NMR

signals due to the minor atropisomers 12c and 12d could not be

confidently assigned.

diphos

compd δ(P₁) δ(P₂) δ(P₃) J ₁₂J ₁₃J ₂₃

dppe

10a

44.8 41.9 -2.5

42.7 42.3 -14.9 24 301 28

46.6 45.4 1.9 38 291 18

49.0 44.1 -14.4 37 293 27

37 292 27

11d ^d,e48.4 45.5^f-12.6 36 292

23 293 28

10b

(S,S)-Chiraphos

11a ^b

11b^c

11c^d,e47.2 45.1 -5.0

g

(R,R)-Me-Duphos 12a ^d

(R,R)-Me-Duphos 12b^d

71.4 73.1 -20.2 26 287 27

70.4 70.0 -9.6 27 310 27

(R,R)-Me-Duphos 12c^d,h67.1 69.6 -14.5 27 298 26

(R,R)-Me-Duphos 12d ^d,h67.4 69.0

g

25 297 26

a

Solvent: THF/THF-d₈for 10, THF-d₈for 11, THF with the

signal locked to a DMSO-d₆insert for 12. The chemical shift is

b

referenced to external 85% H₃PO₄; J values are given in Hz. S_P

(X-ray crystallography, see below). ^cR_P(X-ray crystallography, see

d

below). Absolute configuration not determined. ^eMinor atropi-

somers: 11a is associated with 11d and 11b with 11c. See the

text for details. ^fDoublet of doublets partially obscured by signals

due to 11a . Not observed. Minor atropisomers: ratio 12a :12b:

12c:12d ca. 10:10:2:1.

g

h

F igu r e 6. ORTEP diagram of (S_P)-Pd((S,S)-Chiraphos)-

(o-An)(P(Me)(Ph)(BH₃)) (11a ), with thermal ellipsoids at

the 30% probability level and hydrogen atoms omitted for

clarity.

present in solution. Isolated samples of 11a contained

atropisomer 11d , and 11b contained 11c. The 11b:11c

ratio was consistently ca. 30:1 in isolated samples but

varied from ca. 10 to 20 in the crude material, depending

on reaction conditions for the transmetalation, being

larger when Pd-P bond formation was done at lower

temperature. Purified samples of 11a , and those formed

in situ by reaction of 4 with 2, contained small amounts

of atropisomer 11d . The 11a :11d ratio ranged from ca.

10:1 to 40:1 and seemed to depend on conditions, being

larger when Pd-P bond formation was done at higher

temperature. From these observations, we cannot de-

termine if these atropisomer ratios represent kinetic or

thermodynamic preferences or depend on other solution

components (such as NaOSiMe₃and NaI in transmeta-

lation experiments). For determination of the diaster-

eomeric excess of a sample of 11 (important in studies

of the stereochemistry of reductive elimination and

transmetalation described below), the small amounts of

11c and 11d present were quantified by ¹H NMR

integration and grouped with their parent isomers.

Cr ysta llogr a p h ic Stu d ies. Crystals of 11a were

obtained by slow diffusion of petroleum ether into a

concentrated THF solution of diastereomerically pure

material at -25 °C, and small crystals of 11b crystal-

lized out of the diethyl ether mother liquor obtained

after initial separation of 11a . ORTEP diagrams are

shown in Figures 6 and 7, selected bond lengths and

angles are given in Table 9, and data collection and

structure refinement details are summarized in Table

3.

The structures of the diastereomers, with square-

planar Pd and a distorted-tetrahedral phosphido-

borane group, are similar to each other and to that of

the related complex Pd(dppp)(C₆F₅)((PPh₂)(BH₃)).⁶The

crystal structures provided the absolute configuration

of the P(Me)(Ph)(BH₃) group (S in 11a and R in 11b).

3212 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

Sch em e 6

a

Legend: [Pd] ) Pd(diphos); diphos ) dppe (3, 10), (S,S)-

Chiraphos (4, 11, 13-15), (R,R)-Me-Duphos (5, 12, 16, 17).

F igu r e 7. ORTEP diagram of (R_P)-Pd((S,S)-Chiraphos)-

(o-An)(P(Me)(Ph)(BH₃)) (11b), with thermal ellipsoids at

the 30% probability level and hydrogen atoms omitted for

clarity.

were unable to obtain any NMR data on the crystal used

to obtain the crystal structure of 11a , perhaps due to

the very small size (0.08 × 0.06 × 0.04 mm) of the

crystal.

Ta ble 9. Selected Bon d Len gth s (Å) a n d An gles

(d eg) for Dia ster eom er ic

Red u ctive Elim in a tion . Qualitatively, there was a

correlation between the P-Pd-P bite angles of the

ligands in Pd(diphos)(o-An)(I) complexes 3-7 (Table 4)

and the striking difference in the rates of P-C reductive

elimination from Pd(diphos)(o-An)(P(Me)(Ph)(BH₃)). As

observed previously, larger bite angles (t-Bu-J osiphos,

Tol-Binap)²³are correlated with faster reductive elimi-

nation.²⁸Although the bite angles of dppe and Chira-

phos are nearly identical, the dppe complex reacted

much more quickly at room temperature. This could be

ascribed to the superior donor properties of Chiraphos,

stabilizing Pd(II),²⁹or to the greater structural rigidity

of the Chiraphos complex, which could retard the motion

required to reach the transition state to reductive

elimination.

For dppe complex 10, reductive elimination occurred

over 48 h at room temperature in the presence of o-AnI

to give P(Me)(Ph)(o-An)(BH₃) (1), complex 3, and Pd-

(dppe)₂;³⁰the solution became dark, presumably due to

formation of Pd metal (Scheme 6). In some cases, Pd-

(dppe)I₂was also formed; we have not investigated the

potential effect of light on appearance of this byprod-

uct.³¹

Similarly, Chiraphos complex 11 and Me-Duphos

complex 12 underwent reductive elimination to produce

1. The major Pd products depended on the trapping

agent (Scheme 6) and the temperature. For 11, with 2.5

equiv of o-AnI, reductive elimination was complete after

25 h at 55 °C. The major palladium products were Pd-

((S,S)-Chiraphos)(o-An)(I) (4) and Pd((S,S)-Chiraphos)-

I₂(13) in a ca. 2:1 ratio. At room temperature, in the

presence of o-AnI (1 equiv), the major Pd product was

13. When diphenylacetylene (DPA) was used as a trap

(T ) 50 °C), after 48 h, the major Pd product was Pd-

((S,S)-Chiraphos)(DPA) (14), with a small amount of Pd-

P d ((S,S)-Ch ir a p h os)(o-An )(P (Me)(P h )(BH₃))

Com p lexes 11a a n d 11b

11a

11b

P₃confign

Pd-P₁

S

R

2.312(2)

2.302(2)

2.333(2)

2.038(7)

84.98(7)

99.70(7)

172.64(7)

87.5(2)

2.315(2)

2.3118(18)

2.3338(19)

2.038(8)

85.07(7)

97.11(7)

176.91(8)

88.88(19)

171.7(2)

89.2(2)

116.8(3)

105.8(2)

114.4(4)

111.9(4)

106.6(4)

100.2(4)

1.929(9)

1.831(9)

1.837(8)

Pd-P₂

Pd-P₃

Pd-C₃₆

P₁-Pd-P₂

P₁-Pd-P₃

P₂-Pd-P₃

P₃-Pd-C₃₆

P₁-Pd-C₃₆

P₂-Pd-C₃₆

Pd-P₃-B

Pd-P₃-C₂₉

Pd-P₃-C₃₅

B-P₃-C₂₉

B-P₃-C₃₅

C₂₉-P₃-C₃₅

P₃-B

172.7(2)

88.0(2)

112.8(3)

112.3(2)

113.7(3)

108.9(4)

108.8(4)

99.4(4)

1.944(9)

1.807(8)

1.796(7)

P₃-C₃₅

P₃-C₂₉

Due to the similarity in the scattering factors of the BH₃

and Me groups, it was difficult to differentiate these two

fragments, especially in the lower quality structure of

11a . However, both the P-BH₃and the P-Me bond

lengths in 11a and 11b are in close agreement with the

average values found in the literature (1.825(25) and

1.914(34) Å, respectively).²⁷

The absolute configurations of 11a and 11b were

correlated with their respective NMR spectra by obtain-

ing a ¹H NMR spectrum at 0 °C of the single crystal

used for the X-ray analysis of 11b. Unfortunately, we

(27) (a) For the average P-BH₃bond length see: Brunel, J . M.;

Faure, B.; Maffei, M. Coord. Chem. Rev. 1998, 178-180, 665-698. (b)

For the average P-Me bond length (in PPhMe₂complexes), see: Orpen,

A. G.; Brammer, L.; Allen, F. H.; Kennard, O.; Watson, D. G. J . Chem.

Soc., Dalton Trans. 1989, S1-S84. (c) For crystallographic character-

ization of several related P(Me)(Ar)(BH₃) compounds, see: Stoop, R.

M.; Mezzetti, A.; Spindler, F. Organometallics 1998, 17, 668-675.

Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; J uge´, S. Tetrahedron:

Asymmetry 2000, 11, 3939-3956. Vedejs, E.; Daugulis, O.; Diver, S.

T.; Powell, D. R. J . Org. Chem. 1998, 63, 2338-2341.

(28) Brown, J . M.; Guiry, P. J . Inorg. Chim. Acta 1994, 220, 249-

259.

(29) Gillie, A.; Stille, J . K. J . Am. Chem. Soc. 1980, 102, 4933-4941.

(30) Broadwood-Strong, G. T. L.; Chaloner, P. A.; Hitchcock, P. B.

Polyhedron 1993, 12, 721-729.

(31) Oberhauser, W.; Bachmann, C.; Stampfl, T.; Haid, R.; Bruggeller,

P. Polyhedron 1997, 16, 2827-2835.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3213

Sch em e 7

a

Legend: [Pd] ) Pd(diphos); diphos ) (S,S)-Chiraphos (13-

15, 18), (R,R)-Me-Duphos (16, 17, 19).

((S,S)-Chiraphos)₂(15).³²When no trap was present, 15

and metallic palladium were observed. Reductive elimi-

nation of 12 in the presence of o-AnI gave mostly Pd-

((R,R)-Me-Duphos)I₂(16), and in the absence of o-AnI,

Pd((R,R)-Me-Duphos)₂(17) and Pd metal were formed.

The products 13-17 were synthesized independently

(Scheme 7). Reaction of Pd(COD)Cl₂with 1 equiv of the

appropriate chiral diphosphine produced Pd((S,S)-

Chiraphos)Cl₂(18) and Pd((R,R)-Me-Duphos)Cl₂(19).

Treatment of 18 and 19 with an excess of NaI afforded

13 and 16, respectively. The bis(diphosphine) complexes

15 and 17 were prepared by NaBH₄reduction of

dichlorides 18 and 19 in the presence of Chiraphos or

Duphos, respectively. Similar treatment of 18 with

NaBH(OMe)₃in the presence of diphenylacetylene gave

14.³³

F igu r e 8. ORTEP diagram of Pd((S,S)-Chiraphos)(PhCt

CPh) (14), with thermal ellipsoids at the 30% probability

level and H atoms omitted for clarity. Selected bond lengths

(Å): Pd1-C7 ) 2.052(7), Pd1-C8 ) 2.076(7), Pd1-P2 )

2.322(2), Pd1-P1 ) 2.323(2). Selected bond angles (deg):

C7-Pd1-C8 ) 36.1(3), C7-Pd1-P2 ) 155.9(2), C8-Pd1-

P2 ) 120.7(2), C7-Pd1-P1 ) 116.4(2), C8-Pd1-P1 )

152.5(2), P2-Pd1-P1 ) 86.70(7).

The dihalide complexes 13, 16, and 19 were charac-

terized crystallographically as CH₂Cl₂solvates (see the

Supporting Information for ORTEP diagrams and other

details). As expected, the Pd-P bonds in diiodide

complex 16 (2.2649(12) and 2.2591(13) Å) are longer

than those in dichloride 19 (2.2243(15) and 2.2122(15)

Å), reflecting the trans influence of the halide.³⁴Al-

though Me-Duphos complexes 16 and 19 show negligible

deviations from square-planar geometry, several of the

ligating atoms in Chiraphos complex 13 are displaced

from the PdP₂IC plane, up to 0.25 Å for P₁.

The crystal structures of Pd(0) complexes 14 and 17

were also determined (Figures 8 and 9, Table 3). The

diphenylacetylene in 14 occupies the Pd(Chiraphos)

plane (the dihedral angle between the PdP₂and PdC₂

planes is 8.5°), and the C-C bond length in complexed

diphenylacetylene (1.405(11) Å) is longer than that in

the free ligand (1.198(4) Å).³⁵Complex 17 adopts a

F igu r e 9. ORTEP diagram of Pd((R,R)-Me-Duphos)₂(17)

with thermal ellipsoids at the 30% probability level and

hydrogen atoms omitted for clarity. One of the two mol-

ecules in the unit cell is shown. Selected bond lengths (Å):

Pd1-P51 ) 2.3001(7), Pd1-P1 ) 2.3036(8), Pd1-P31 )

2.3127(8), Pd1-P21 ) 2.3194(7). Selected bond angles

(deg): P51-Pd1-P1 119.90(3), P51-Pd1-P31 ) 87.09(3),

P1-Pd1-P31 ) 118.37(3), P51-Pd1-P21 ) 113.08(3),

P1-Pd1-P21 ) 86.83(3), P31-Pd1-P21 ) 135.13(3).

(32) (a) Visentin, G.; Piccolo, O.; Consiglio, G. J . Mol. Catal. 1990,

61, L1-L5. (b) Genet, J .-P.; Grisoni, S. Tetrahedron Lett. 1988, 29,

4543-4546. (c) Elmes, P. S.; J ackson, W. R. Ann. N. Y. Acad. Sci. 1980,

225-228.

(33) For analogous Pd(diphos)(PhCtCPh) and Pd(PR₃)₂(PhCtCPh)

complexes, see: (a) Reference 19. (b) Tanaka, Y.; Yamashita, H.;

Shimada, S.; Tanaka, M. Organometallics 1997, 16, 3246-3248. (c)

Ozawa, F.; Sugawara, M.; Hayashi, T. Organometallics 1994, 13,

3237-3243. (d) Portnoy, M.; Milstein, D. Organometallics 1994, 13,

600-609. (e) Pan, Y.; Mague, J . T.; Fink, M. J . J . Am. Chem. Soc. 1993,

115, 3842-3843. (f) Schager, F.; Bonrath, W.; Po¨rschke, K.-R.; Kessler,

M.; Kru¨ger, C.; Seevogel, K. Organometallics 1997, 16, 4276-4286.

(g) Paonessa, R. S.; Prignano, A. L.; Trogler, W. C. Organometallics

1985, 4, 647-657.

(34) Appleton, T. G.; Bennett, M. A. Inorg. Chem. 1978, 17, 738-

747. For an earlier report of the structure of 19‚CH₂Cl₂, see: Malaise´,

G.; Barloy, L.; Osborn, J .; Kyritsakas, N. C. R. Chim. 2002, 5, 289-

296.

(35) Mavridis, A.; Moustakali-Mavridis, I. Acta Crystallogr. 1977,

B33, 3612.

distorted-tetrahedral structure, with a dihedral angle

between the two PdP₂planes of 80.4°.

Ster eoch em istr y of Redu ctive Elim in ation .Knowl-

edge of the absolute configurations of 11a and 11b and

of the enantiomers of PAMP-BH₃(1) allowed direct

observation of the stereochemistry of reductive elimina-

tion. In analogous C-X (X ) N, S, O) reductive elimina-

tions from Pd(II), adding a trap for Pd(0) improved the

yield and/or selectivity of the reaction.³⁶Similarly, after

screening several trapping agents (none, o-AnI, (S,S)-

Chiraphos), we found that using an excess of diphenyl-

3214 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

Sch em e 8

inversion under these conditions, but the rates of these

processes are competitive.

Similar dynamic kinetic resolution (26% de) was

observed in toluene on a larger scale. Because of the

limited solubility of 4 in toluene, NMR-scale experi-

ments such as those in Table 11 were not possible in

this solvent. On a preparative scale, however, these

observations provided a convenient, high-yield route to

11a without requiring synthesis of enantiopure (R_P)-2.

Thus, treatment of 4 with 2 equiv of racemic 2 in toluene

gave 11a in 80% isolated yield; as expected, unreacted

2, isolated by chromatography, was enriched in the S

enantiomer (ee ca. 30% by chiral HPLC).

These observations show that Pd complex 4 is a highly

reactive electrophile, since transmetalation occurs be-

fore racemization of enantioenriched (P(Me)(Ph)(BH₃))^-

at -78 °C. Livinghouse reported similar behavior of this

anion and closely related ones with the potent alkylating

agent 2-(chloromethyl)benzothiophene.^38aOur brief sur-

vey of reaction conditions for transmetalation of 4

showed that temperature and solvent both affected the

diastereoselectivity. To study similar behavior with an

organic electrophile, we used p-methoxybenzyl chloride.

This compound is commercially available, in contrast

to the benzothiophene derivative,⁴⁰and the ee of the

product (19, Scheme 11) was readily determined by

chiral HPLC. Alkylations were performed in THF at

-78 °C with a variety of bases. The results (Table 12)

confirm the sensitivity of such reactions to the nature

of the base, to the resulting counterion, and to additives

such as HMPA and provide another benchmark for the

reactivity of Chiraphos complex 4.

Con clu sion . Several Pd(diphos)(o-An)(I) complexes

were prepared and tested in the catalytic asymmetric

synthesis of P(Me)(Ph)(o-An)(BH₃). Although Pd((R,S)-

t-Bu-J osiphos)(o-An)(I) (6) was a robust catalyst, the

reaction was slow and the enantioselectivity (e10% ee)

was poor. However, both these observations and Brown’s

related work⁹demonstrate that chiral phosphine-

boranes can be successfully prepared via Pd-catalyzed

asymmetric phosphination.

Our results provide two targets for rational improve-

ment of these reactions. First, the direct observations

of transmetalation stereochemistry for Chiraphos com-

plex 4 show that interconversion of the enantiomeric

phosphido-borane anions (P(Me)(Ph)(BH₃))^-is com-

petitive in rate with transmetalation, not much faster,

as desired (Scheme 1). Second, these experiments also

show that the rates of transmetalation of these enan-

tiomers are not strikingly different, again unlike the

idealized Scheme 1. Although this system is not cata-

lytically active, it is plausible that these ideas are

relevant to catalysis with other complexes. Therefore,

P inversion (anion interconversion) could be accelerated

by using bulkier P substituents and/or by replacing the

P-Me with a P-Ar group,⁷and transmetalation selec-

tivity could be improved by employing P substituents

more sterically different than Me and BH₃. We are

currently investigating these approaches.

acetylene resulted in the cleanest reductive elimination.

Heating either diastereomer of 11 to 50 °C in the

presence of 4 equiv of diphenylacetylene gave PAMP-

BH₃and Pd((S,S)-Chiraphos)(PhCtCPh) (14) as the

major products, along with anisole and other unidenti-

fied MeO-containing byproducts (Scheme 8). Some Pd-

((S,S)-Chiraphos)₂(15) was observed by ³¹P NMR, as

well as formation of small amounts of solid, presumably

Pd metal. Since continued heating led to further de-

composition, thermolyses were not run to complete

conversion (Table 10).

Workup by preparative TLC gave pure PAMP-BH₃

in high ee (chiral HPLC), with retention of configuration

at phosphorus. Diastereomers 11a and 11b undergo

reductive elimination at different rates; approximate

half-lives under these conditions are 30 and 10 h,

respectively. Interestingly, when a smaller excess (1.1

equiv) of diphenylacetylene was present to trap Pd(0),

some erosion in the stereochemistry was observed. The

origin of anisole and the other unidentified byproducts

remains unclear; likewise, the mechanism of formation

of the arene byproduct in Pd-catalyzed aryl amination

could not be elucidated.³⁷

Ster eoch em istr y of Tr a n sm eta la tion . Treatment

of 4 with highly enantioenriched (S_P)- or (R_P)-2³⁸and

NaOSiMe₃in THF-d₈at -78 °C gave (R_P)-11b or (S_P)-

11a , respectively, in high de, with retention of configu-

ration at phosphorus (Scheme 9 and Table 11, entries

1 and 2; the apparent inversion is due to the change in

priority for assigning absolute configuration). The ero-

sion of stereochemistry in room-temperature transmeta-

lation (entries 7 and 8) is presumably due to inversion

of the phosphido-borane anion before reaction with the

Pd complex occurs (Scheme 10, see also Scheme 1).³⁹

Study of transmetalation at a variety of temperatures

provided qualitative information on the relative rates

of inversion and Pd-P bond formation (entries 3-6).

With racemic 2, dynamic kinetic resolution was ob-

served (Scheme 10 and Table 11, entry 9); one enanti-

omer of the anion (P(Me)(Ph)(BH₃))^-appears to react

more quickly with chiral 4 than the other (k_R> k_S), and

anion interconversion can occur before transmetalation.

This is consistent with the greater loss of stereochemical

information in entry 7 vs entry 8 and suggests that

transmetalation occurs somewhat more quickly than P

(36) (a) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1997, 119,

8232-8245. (b) Mann, G.; Baranano, D.; Hartwig, J . F.; Rheingold, A.

L.; Guzei, I. A. J . Am. Chem. Soc. 1998, 120, 9205-9219. (c) Widen-

hoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J . Am. Chem. Soc. 1997,

119, 6787-6795.

(37) Hamann, B. C.; Hartwig, J . F. J . Am. Chem. Soc. 1998, 120,

3694-3703.

(38) (a) Wolfe, B.; Livinghouse, T. J . Org. Chem. 2001, 66, 1514-

1516. (b) References 2c and 5.

Studies of the stoichiometric steps in the asymmetric

phosphination led to separation, isolation, and deter-

mination of the absolute configuration of the Pd phos-

(40) Ca u tion ! We found that 2-(chloromethyl)benzothiophene caused

severe contact dermatitis and suggest that special care be used in

handling this compound.

(39) (a) Oshiki, T.; Hikosaka, T.; Imamoto, T. Tetrahedron Lett.

1991, 32, 3371-3374. (b) Reference 7b.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3215

Ta ble 10. Ster eoch em istr y of Red u ctive Elim in a tion of P AMP -BH₃fr om

P d ((S,S)-Ch ir a p h os)(o-An )(P (Me)(P h )(BH₃)) (11a a n d 11b)^a

isomer (de (%))^bamt of DPA (equiv) time (h) conversn (%)^cPAMP-BH₃yield (%)^dee (%)^eother product yield (%)^fdec (%)^g

11a (89)

11a (88)

11a (94)

11b (100)

11b (88)

1.2

4

72

96

42

37

48

79

55

84

87

98

96

91

39 (20) (48, 25)

36 (18) (65, 32)

51 (21) (61, 25)

73 (20) (83, 23)

62 (20) (63, 20)

62 (27) (64, 28)

54 (20) (56, 21)

70 (21) (78, 24)

75 (85)

69 (80)

91 (93)

87 (93)

77

4, 6, 4

0, 3, 3

4, 4, 0

3, 3, 0

1, 3, 8

6, 0, 9

2, 1, 0

3, 5, 0

31

15

27

10

24

21

40

12

4

1.5

1.2

4

77

98

93 (92)

4

a

b

For details, see the Experimental Section. The de value was determined by integration of the MeO signals in the initial ¹H NMR

spectrum, including the atropisomers 11c and 11d . ^cConversion of 11 was determined by integration of its MeO signals at the beginning

and end of the reaction. Yields of PAMP-BH₃were determined by NMR integration (MeO resonance). Isolated yields are in parentheses.

d

The figures in italics are NMR and isolated yields corrected for incomplete conversion. ^eThe ee value was determined by chiral HPLC

(Chiralpak AD; see the Experimental Section). Because the diastereomers of 11 undergo reductive elimination at different rates, experiments

involving incomplete conversion and in which 11 is not diastereopure are expected to lead to PAMP-BH₃products with ee values different

from the initial de of 11. In these cases, the theoretical maximum ee of 11 is given in parentheses, as determined by NMR integration

(MeO signals). ^fSeveral MeO-containing products were observed. These include unknown impurities with MeO signals at δ 3.84 (X) and

3.65 (Z) and anisole (Y, δ 3.74). Their NMR yields were determined by integration. ^gThe extent of decomposition was measured by comparing

the integration of the initial MeO signals of 11 with the integrals of the products (PAMP-BH₃and other products). The incomplete mass

balance is reflected in the percent decomposition. In some cases, the sum of the yields of PAMP-BH₃and X, Y, and Z is not 100%, due

to rounding errors.

Sch em e 9

Sch em e 10

Sch em e 11

Ta ble 11. Ster eoch em istr y of P d -P Bon d

F or m a tion (Tr a n sm eta la tion ) in Rea ction of 4 w ith

2 a n d Na OSiMe₃in THF -d ₈

entry

temp (°C)

ee of 2 (%)^a

de of 11 (%)^b

1

2

3

4

5

6

7

8

9

-78

-60

-45

-15

0

21

95 (R)

99 (S)

97 (S)

95 (R)

0

94 (S)^c

94 (R)

93 (R)

88 (R)

80 (R)

63 (R)

86 (S)^d

23 (S)^d

Ta ble 12. F or m a tion of 19 by Alk yla tion of

(S_P)-P H(Me)(P h )(BH₃) (2) w ith p-Meth oxyben zyl

Ch lor id e in THF a t -78 °C: Dep en d en ce of

P r od u ct Ster eoch em istr y on th e Ba se

entry

ee of 2 (%)^a

base

ee of 19 (%)^b

1

2

3

4

99

97

94

n-BuLi/2 equiv HMPA^c

0

30

76

12

n-BuLi^c

NaOSiMe₃

KN(SiMe₃)₂

a

b

From chiral HPLC (Chiralpak OJ -H). From integration of

the ¹H NMR spectrum; the ee and de values obtained at -78 °C

a

b

From chiral HPLC (Chiralpak OJ -H). From chiral HPLC

(Chiralpak AD). ^cn-BuLi was used as a solution in hexanes.

(entries

1 and 2) are the same, within experimental error.

^cAverage of two runs. Average of three runs.

d

Exp er im en ta l Section

phido-borane complexes Pd((S,S)-Chiraphos)(o-An)-

(P(Me)(Ph)(BH₃)) (11a and 11b). Treatment of Pd((S,S)-

Chiraphos)(o-An)(I) (4) with highly enantioenriched 1

and NaOSiMe₃yielded highly diastereoenriched Pd-

((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH₃)) (11), which

formed highly enantioenriched PAMP-BH₃(2) by re-

ductive elimination; both reactions proceed with reten-

tion of configuration at phosphorus. These observations

provide detailed mechanistic information on this useful

class of Pd-mediated reactions and have more general

significance in confirming long-held assumptions about

the stereochemistry of reductive elimination, while

suggesting that the reactions of M-P and M-C bonds

are similar in stereochemistry.

Gen er a l Deta ils. Unless otherwise noted, all reactions and

manipulations were performed in dry glassware under a

nitrogen atmosphere at room temperature in a drybox or using

standard Schlenk techniques. Petroleum ether (bp 38-53 °C),

ether, THF, CH₂Cl₂, and toluene were dried and degassed

using columns containing activated alumina⁴¹or dried and

distilled before use from Na/benzophenone (CH₂Cl₂was dis-

tilled from CaH₂).

Unless otherwise noted, all NMR spectra were recorded on

a Varian 500 MHz spectrometer. ¹H and ¹³C NMR chemical

shifts are reported relative to Me₄Si and were determined by

reference to the residual ¹H or ¹³C solvent peaks. ³¹P NMR

(41) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;

Timmers, F. J . Organometallics 1996, 15, 1518-1520.

3216 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

chemical shifts are reported relative to H₃PO₄(85%) used as

an external reference. Unless otherwise noted, peaks in NMR

spectra are singlets; J values are given in Hz. Infrared spectra

were recorded on KBr pellets with a Perkin-Elmer 1600 series

FTIR instrument and are reported in cm^-1. Elemental analyses

were provided by Schwarzkopf Microanalytical Laboratory.

Mass spectra were obtained at the University of Illinois

Urbana-Champaign.

The following compounds were prepared using previously

reported procedures: Pd(dba)₂,⁴²Pd(PPh₃)₄,⁴³Pd(COD)Cl₂,⁴⁴

PH(Me)(Ph),⁴⁵and (S_P)-PH(Me)(Ph)(BH₃).^38a(R_P)-PH(Me)(Ph)-

(BH₃) was prepared using a modification of the literature

method; (-)-menthol gave (S_P)-PH(Me)(Ph)(BH₃) as the major

product as reported, but (+)-menthol yielded (R_P)-PH(Me)(Ph)-

(BH₃) as the major product.^2c,eThe ee of PH(Me)(Ph)(BH₃) was

determined by chiral HPLC (Chiralcel OJ -H, 10% i-PrOH/

hexane, flow rate 1 mL/min; retention times are 12.1 (R) and

12.9 min (S)).

P H(Me)(P h )(BH₃) (1). PH(Me)(Ph) (3.18 g, 0.026 mol) was

slowly transferred by cannula to a stirred solution of BH₃‚THF

(27.8 mL of a 1.0 M solution in THF, 0.028 mol). The solvent

was removed in vacuo, and petroleum ether was added to the

cloudy oil. The mixture was filtered over a fine frit loaded with

silica gel, and the silica gel was rinsed with petroleum ether

(300 mL). The mixture was concentrated in vacuo to ca. 25

mL and filtered through Celite. The rest of the solvent was

removed in vacuo to yield a clear oil, which should be stored

under nitrogen to prevent decomposition. ³¹P{¹H} NMR

(CDCl₃): δ -14 (br).

tr a n s-P d (P P h ₃)₂(o-An )(I). This complex was prepared by

a modification of a literature procedure.¹⁴To a bright yellow

stirred suspension of Pd(PPh₃)₄(2.00 g, 1.73 mmol) in toluene

(10 mL) was added o-AnI (343 µL, 2.64 mmol, 1.5 equiv), which

caused the suspension to become pale yellow. The suspension

was stirred under N₂for 1 h and was then filtered. The pale

yellow solid was washed with diethyl ether (3 × 15 mL) to

yield 1.20 g (80%) of crude product, which was used in

subsequent reactions without further purification. ³¹P{¹H}

NMR (THF): δ 25.1.¹⁴

At this temperature, both dba and the product precipitated

from solution. As the solution was warmed to room tempera-

ture, however, the dba redissolved and more product was

collected as a yellow solid. Recrystallization from CH₂Cl₂/

diethyl ether afforded yellow crystals suitable for crystal-

lographic and elemental analysis. Three crops of product were

obtained (total yield: 1.21 g, 75% yield).

¹H NMR (300 MHz, CDCl₃): δ 7.21-7.18 (m, 1H, Ar), 6.88-

6.83 (m, 1H, Ar), 6.82-6.64 (m, 1H, Ar), 6.52-6.49 (m, 1H,

Ar), 3.85 (3H, OMe), 2.82-2.53 (m, 4H, CH₂), 2.73 (3H, Me),

2.72 (3H, Me), 2.39 (3H, Me), 2.34 (3H, Me). ¹³C{¹H} NMR

(CDCl₃): δ 161.7 (quat, Ar), 137.4 (Ar), 130.0 (quat, Ar), 123.4

(Ar), 119.7 (Ar), 109.7 (Ar), 61.9 (CH₂), 58.3 (CH₂), 55.6 (OMe),

50.0 (Me), 49.9 (Me), 49.6 (Me), 49.1 (Me). IR: 2911, 2879,

1728, 1556, 1450, 1283, 1222, 1172, 1117, 1050, 1022, 950, 800,

750, 722, 694, 500, 472. Anal. Calcd for C₁₃H₂₃IN₂OPd‚0.36CH₂-

Cl₂: C, 32.94; H, 4.91; N, 5.75. Found: C, 32.91; H, 4.90; N,

5.70 (the presence of solvent was quantitatively confirmed by

NMR).

P d (d p p e)(o-An )(I) (3). To a solution of trans-Pd(PPh₃)₂(o-

An)(I) (536 mg, 0.620 mmol) in toluene (4 mL) was added a

solution of dppe (272 mg, 0.682 mmol) in toluene (4 mL). The

pale yellow suspension was stirred for 45 min, and the toluene

was removed in vacuo. Petroleum ether (7 mL) was added, and

the solution was stirred for 12 h. The air-stable, pale yellow

solid was collected on a fine frit and dried to yield 289 mg (63%)

of crude product. A sample was purified for analysis by

recrystallization from CHCl₃/ether at -25 °C; recrystallization

from THF at -25 °C afforded crystals for crystallographic

analysis.

¹H NMR (CDCl₃): δ 8.07-7.80 (broad m, 7H, Ar), 7.48

(broad m, 10H, Ar), 7.22-6.90 (m, 4H, Ar), 6.75-6.71 (m, 1H,

Ar), 6.57-6.52 (m, 1H, Ar), 6.19-6.15 (m, 1H, Ar), 3.22 (3H,

OMe), 2.42 (broad m, 4H, CH₂). ¹³C{¹H} NMR (CD₂Cl₂): δ

161.5 (Ar, quat), 141.6 (d, J ) 128, Ar, quat), 138.2 (d, J ) 2,

Ar), 134.5-128.2 (m, br, Ar), 124.3 (Ar), 120.4 (d, J ) 5, Ar),

109.8 (d, J ) 3, Ar), 54.5 (OMe), 29.0 (dd, J ) 17, 13, CH₂),

25.0 (dd, J ) 16, 8, CH₂). ³¹P{¹H} NMR (CDCl₃): δ 50.5 (d, J

) 26), 35.2 (d, J ) 26). IR: 3044, 2922, 2811, 1556, 1483, 1456,

1428, 1306, 1222, 1178, 1100, 1050, 1017, 994, 878, 817, 739,

693, 530, 487. Anal. Calcd for C₃₃H₃₁IOP₂Pd: C, 53.65; H, 4.23.

Found: C, 53.59; H, 4.22.

P d ((S,S)-Ch ir a p h os)(o-An )(I) (4). Meth od 1. To a solu-

tion of trans-Pd(PPh₃)₂(o-An)(I) (203 mg, 0.234 mmol) in

toluene (6 mL) was added a solution of (S,S)-Chiraphos (100

mg, 0.234 mmol) in toluene (6 mL). The pale yellow suspension

was stirred at room temperature for 72 h. The toluene was

removed in vacuo. Petroleum ether (12 mL) was added, and

the suspension was stirred for 24 h. The air-stable, yellow solid

was collected on a fine frit and dried to yield 80 mg (48%) of

crude product.

Meth od 2. To a stirred solution of Pd(TMEDA)(o-An)(I) (9;

1.000 g, 2.19 mmol) in THF (5 mL) was added, dropwise, a

solution of (S,S)-Chiraphos (934 mg, 2.19 mmol) in THF (5

mL). The solution was stirred for 24 h, and a yellow solid

precipitated. The solid was collected on a fine frit, rinsed with

THF (0.5 mL) and petroleum ether (20 mL), and dried on the

frit to yield 1.212 g (72% yield) of analytically pure product.

The washes were combined with the original mother liquor,

and a second crop precipitated at room temperature (total yield

1.437 g, 85% yield).

NMR spectra showed two atropisomers (A and B) in a 6:1

ratio. ¹H NMR (300 MHz, CD₂Cl₂): δ 8.10-8.04 (m, 1H A, 5H

B, Ar), 7.89-7.83 (m, 3H A, Ar), 7.70-7.47 (m, 11H A, 8H B,

Ar), 7.37-7.32 (m, 1H A, 2H B, Ar), 7.25-7.23 (m, 3H B, Ar),

7.18-7.14 (m, 2H A, Ar), 6.99-6.94 (m, 1H A, 2H B, Ar), 6.83-

6.70 (m, 3H A, 3H B, Ar), 6.50-6.45 (m, 1H A, 1H B, Ar), 6.12-

6.08 (m, 1H A, Ar), 3.35 (3H B, OMe), 3.14 (3H A, OMe), 2.44-

2.33 (m, 1H A, 1H B, CH), 2.19-2.04 (m, 1H A, 1H B, CH),

1.10-0.97 (m, 6H A, 6H B, Me). ¹³C{¹H} NMR (CD₂Cl₂): δ

161.7 (Ar), 143.1 (d, J ) 127, Ar, quat), 137.5 (Ar), 137.2 (d, J

{P d [P (o-Tol)₃](o-An )(µ-I)}₂(8). To a suspension of Pd-

(dba)₂(1.00 g, 1.75 mmol) in toluene (15 mL) was added a

solution of P(o-Tol)₃(1.07 g, 3.50 mmol, 2 equiv) in toluene

(10 mL) and a solution of o-AnI (1.14 mL, 8.75 mmol, 5 equiv)

in toluene (5 mL). The purple-brown suspension was diluted

to 60 mL with toluene. The mixture was stirred for 75 min

and filtered. The orange filtrate was concentrated to 20 mL,

and diethyl ether (200 mL) was added. Cooling to -25 °C for

7 days precipitated an air-stable orange solid, which was

collected on a fine frit and washed with petroleum ether (10

mL) to give 572 mg (51%) of crude, sparingly soluble product.

A sample could be purified for elemental analysis by recrys-

tallization from CH₂Cl₂/diethyl ether at -25 °C.

³¹P{¹H} NMR (CHCl₃): δ 27.6 (broad). IR: 3044, 2923, 1455,

1384, 1228, 1022, 748, 698, 535, 467. Anal. Calcd for

C

₅₆H₅₆I₂O₂P₂Pd₂: C, 52.16; H, 4.38. Found: C, 52.12; H, 4.21.

P d (TMEDA)(o-An )(I) (9). To a stirred suspension of Pd-

(dba)₂(2.03 g, 3.55 mmol) in toluene (20 mL) were added

TMEDA (697 µL, 4.62 mmol) and o-iodoanisole (660 µL, 5.08

mmol) under N₂. The reaction mixture was heated to 55 °C,

at which point it turned green and became homogeneous. Once

cooled back to room temperature, the reaction mixture was

filtered to remove suspended Pd metal particles. The solvent

was then removed from the filtrate in vacuo to yield an air-

stable yellow solid. This product was washed with diethyl ether

(3 × 10 mL) and collected on a fine frit. The diethyl ether

fraction was concentrated to ca. 20 mL and cooled to -25 °C.

(42) Rettig, M. F.; Maitlis, P. M. Inorg. Synth. 1990, 28, 110-113.

(43) Coulson, D. R. Inorg. Synth. 1990, 28, 107-109.

(44) Drew, D.; Doyle, J . R. Inorg. Synth. 1990, 28, 346-349.

(45) Roberts, N. K.; Wild, S. B. J . Am. Chem. Soc. 1979, 101, 6254-

6260.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3217

) 13, Ar), 136.8 (d, J ) 13, Ar), 132.9 (d, J ) 9, Ar), 132.3 (d,

J ) 3, Ar), 131.9 (d, J ) 8, Ar), 131.7 (Ar), 130.4 (d, J ) 2, Ar),

130.0 (d, J ) 3, Ar), 129.8 (d, J ) 57, Ar, quat), 129.0 (Ar),

128.9 (Ar), 128.8 (Ar), 128.7 (d, J ) 3, Ar), 128.58 (d, J ) 2,

Ar), 128.4 (Ar), 128.3 (Ar), 128.2 (Ar), 128.03 (Ar), 127.7 (Ar),

126.1 (d, J ) 45, Ar, quat), 124.2 (Ar), 120.0 (d, J ) 8, Ar),

109.9 (d, J ) 5, Ar), 54.5 (OMe), 36.8 (dd, J ) 27, 23, CH),

34.0 (dd, J ) 24, 15, CH), 14.4-13.9 (m, Me). ³¹P{¹H} NMR

(CDCl₃): δ 56.5 (d, J ) 39, B), 55.4 (d, J ) 36, A), 42.5 (d, J )

39, B), 41.8 (d, J ) 36, A). IR: 3036, 2966, 2907, 1560, 1482,

1449, 1431, 1219, 1102, 1055, 1020, 743, 690, 544, 520. Anal.

Calcd for C₃₅H₃₅IOP₂Pd: C, 54.82; H, 4.60. Found: C, 54.83;

H, 4.71.

¹H NMR (CDCl₃): δ 8.47-8.42 (m, 1H B, Ar), 7.90-7.84 (m,

2H A, Ar), 7.66-7.59 (m, 3H B, Ar), 7.48-7.34 (m, 8H A, Ar),

7.17-7.12 (m, 1H B, Ar), 6.98-6.92 (m, 2H B, Ar), 6.91-6.83

(m, 2H B, Ar), 6.75-6.69 (m, 1H B, Ar), 6.67-6.60 (m, 1H A,

Ar), 6.48-6.44 (m, 1H B, Ar), 6.32-6.22 (m, 1H A, 1H B, Ar),

6.15-6.10 (m, 2H A, Ar), 5.74-5.69 (m, 1H B, Ar), 4.62-4.60

(m, 1H B, Cp), 4.54-4.51 (m, 1H A, Cp), 4.38-4.36 (m, 1H B,

Cp), 4.34-4.33 (m, 1H B, Cp), 4.26-4.25 (m, 1H A, Cp), 3.82-

3.78 (m, 6H A, Cp), 3.70 (5H B, Cp), 3.49-3.40 (m, 4H A, OMe,

CHMe), 3.20 (3H B, OMe), 3.17 (q, J _HH) 4, 1H B, CHMe),

2.14-2.09 (m, 3H A, Me), 2.10-2.06 (m, 3H B, Me), 1.76 (d,

J _PH) 12, 9H A, 9H B, t-Bu), 1.47 (d, J _PH) 13, 9H B, t-Bu),

1.38 (d, J _PH) 13, 9H A, t-Bu). ¹³C{¹H} NMR (CDCl₃): δ 160.7

(B, Ar, quat), 160.6 (d, J ) 3, A, Ar, quat), 141.4 (A, Ar), 138.0

(dd, J ) 138, 6, A, Ar, quat), 136.8 (d, J ) 15, B, Ar), 134.4 (d,

J ) 13, A, Ar), 134.0 (d, J ) 10, A, Ar), 132.8 (d, J ) 9, B, Ar),

132.3 (d, J ) 47, A, Ar, quat), 131.9 (d, J ) 63, A, Ar, quat),

130.1 (d, J ) 2, A, Ar), 129.6 (d, J ) 3, A, Ar), 128.2 (d, J )

11, B, Ar), 128.0 (B, Ar), 127.6 (d, J ) 20, A, Ar), 127.3 (d, J

) 11, A, Ar), 125.6 (d, J ) 10, B, Ar), 123.8 (B, Ar), 123.5 (A,

Ar), 120.3 (d, J ) 9, A, Ar), 108.6 (B, Ar), 107.9 (d, J ) 4, A,

Ar), 96.2 (dd, J ) 18, 7, A, Cp, quat), 79.1 (dd, J ) 35, 10, A,

Cp, quat), 74.8 (d, J ) 4, A, Cp, CH), 70.4 (B, Cp), 70.1 (A,

Cp), 69.3 (d, J ) 8, A, Cp, CH), 67.8 (A, Cp, CH), 53.7 (A, OMe),

53.2 (B, OMe), 39.5 (B, CMe₃), 38.8 (A, CMe₃), 38.3 (B, CMe₃),

36.7 (d, J ) 2, A, CMe₃), 33.7 (d, J ) 8, A, CH), 33.2 (br, B,

CMe₃), 32.6 (d, J ) 4, A, CMe₃), 31.4 (d, J ) 4, A, CMe₃), 31.3

(B, CMe₃), 19.0 (d, J ) 6, B, Me), 18.2 (d, J ) 6, A, Me). ³¹P-

{¹H} NMR (CDCl₃): δ 78.5 (d, J ) 38, A), 70.2 (d, J ) 36, B),

21.5 (d, J ) 36, B), 15.9 (d, J ) 38, A). IR: 2921, 2852, 1734,

1560, 1492, 1453, 1385, 1223, 1176, 1162, 1100, 1051, 1018,

746, 697. Anal. Calcd for C₃₉H₄₇FeIOP₂Pd: C, 53.06; H, 5.37.

Found: C, 53.12; H, 5.39.

P d ((R)-Tol-Bin a p )(o-An )(I) (7). To a suspension of {Pd-

[P(o-Tol)₃](o-An)(I)}₂(8; 390 mg, 0.302 mmol) in toluene (20

mL) was added a solution of (R)-Tol-Binap (410 mg, 0.605

mmol) in toluene (5 mL). The orange-brown suspension was

stirred at room temperature for 24-30 h, at which point it

appeared to be homogeneous. The solution was filtered by

cannula, and the filtrate was pumped dry. The granular off-

white solid contained a small amount of a purple impurity,

which was removed by washing with petroleum ether. Tritu-

ration with ether (75 mL) gave a yellow solid product. The solid

was then collected and recrystallized from THF/petroleum

ether at -25 °C to yield 308 mg of product (49%). Two

atropisomers (A and B), whose ¹H NMR spectra were not

resolved in the aryl region, were observed in a 1.8:1 ratio.

¹H NMR (C₆D₆): δ 8.65-8.63 (m, 1H B, Ar), 8.25-8.05 (m,

3H A, 3H B, Ar), 7.74 (m, 2H A, 2H B, Ar), 7.60-7.57 (m, 1H

A, 2H B, Ar), 7.33-7.20 (m, 2H A, 2H B, Ar), 7.12-6.90 (m,

11H A, 11H B, Ar), 6.82-6.77 (m, 2H A, 2H B, Ar), 6.65-6.53

(m, 6H A, 6H B, Ar), 6.23-6.21 (m, 3H A, 3H B, Ar) 6.10 (br,

2H A, 2H B, Ar), 3.67 (3H, B, OMe), 3.64 (3H, A, OMe), 2.09

(3H A, Me; 3H B, Me), 1.79-1.64 (overlapping s, 9H, A, Me;

9H, B, Me). ¹³C{¹H} NMR (C₆D₆): δ 161.9 (Ar), 140.4 (m, Ar),

139.9-139.5 (m, Ar), 138.0-137.2 (m, Ar), 136.6 (m, Ar),

135.6-133.6 (m, Ar), 131.0-130.1 (m, Ar), 129.8 (Ar), 129.6-

129.4 (m, Ar), 127.0 (Ar), 126.8 (Ar), 126.4 (Ar), 124.6 (Ar),

123.9 (Ar), 122.6 (Ar), 121.0 (Ar), 114.0 (Ar), 111.7 (Ar), 110.5

(Ar), 56.0 (A, OMe), 55.9 (B, OMe), 21.7-21.3 (overlapping s,

tol-Me). ³¹P{¹H} NMR (C₆D₆): δ 23.8 (d, J ) 37, A), 23.4 (d, J

) 38, B), 12.3 (d, J ) 37, A), 10.4 (d, J ) 38, B). IR: 3044,

2933, 1556, 1494, 1450, 1256, 1217, 1189, 1094, 1022, 800, 744,

700, 633, 522, 500. Anal. Calcd for C₅₅H₄₇IOP₂Pd: C, 64.81;

H, 4.65. Found: C, 64.91; H, 4.63.

P d ((R,R)-Me-Du p h os)(o-An )(I) (5). A solution of Pd-

(TMEDA)(o-An)(I) (9; 255 mg, 0.558 mmol) and (R,R)-Me-

Duphos (171 mg, 0.558 mmol) in THF (3 mL) was stirred at

room temperature for 24 h. The yellow product was precipi-

tated by the addition of petroleum ether, collected, and further

washed with petroleum ether. Yield: 235 mg (65%). A sample

was prepared for elemental and crystallographic analysis by

recrystallization from CH₂Cl₂/Et₂O at -25 °C. Complex 5

cocrystallized with 1 equiv of CH₂Cl₂according to X-ray

crystallography. Desolvation occurred prior to elemental analy-

sis to yield a final Pd:CH₂Cl₂ratio of 10:1. A 4.5:1 ratio of

atropisomers A and B was observed by NMR.

¹H NMR (CDCl₃): δ 7.75-7.67 (m, 1H A, 1H B, Ar), 7.64-

7.58 (m, 4H A, 3H B, Ar), 7.24-7.21 (m, 1H B, Ar), 6.97-6.92

(m, 1H A, 1H B, Ar), 6.83-6.80 (m, 1H A, 1H B, Ar), 6.67-

6.63 (m, 1H A, 1H B, Ar), 3.78-3.70 (m, 1H A, 1H B, CH),

3.74 (3H B, OMe), 3.72 (3H A, OMe), 3.16-3.09 (m, 1H B, CH),

2.89-2.78 (m, 1H A, CH), 2.65-2.60 (m, 1H B, CH), 2.57-

2.45 (m, 2H A, CH₂), 2.39-2.29 (m, 1H A, 1H B, CH), 2.25-

1.80 (m, 6H A, 3CH₂), 1.67-1.54 (9H B, Me + 3CH₂), 1.57 (dd,

J _PH) 20, J _HH) 7, 3H A, Me), 1.44 (dd, J _PH) 19, J _HH) 7, 3H

A, Me), 1.24 (dd, J _PH) 20, J _HH) 7, 3H B, Me), 1.02-0.87 (m,

7H A, 2Me +CH; 6H B, 2Me), 0.81-0.77 (m, 2H B, CH₂). ¹³C-

{¹H} NMR (CDCl₃): δ 163.5 (B, Ar), 162.0 (A, Ar), 144.7 (d, J

) 130, A, Ar, quat), 144.5 (dd, J ) 44, 34, A, Ar, quat), 143.0

(dd, J ) 33, 27, A, Ar, quat), 140.7 (A, Ar), 136.5 (B, Ar), 133.42

(d, J ) 9, B, Ar), 133.36 (d, J ) 15, A, Ar), 132.7 (d, J ) 16, A,

Ar), 132.6 (B, Ar), 131.5-131.3 (m, A, Ar), 124.4 (A, Ar), 120.8

(d, J ) 5, A, Ar), 111.5 (d, J ) 5, A, Ar), 109.6 (d, J ) 5, B,

Ar), 56.1 (A, OMe), 53.7 (B, OMe), 44.4 (d, J ) 29, A, CH),

43.0 (d, J ) 22, A, CH), 42.8 (d, J ) 23, B, CH), 42.7 (d, J )

28, B, CH), 38.0 (d, J ) 1, A, CH₂), 37.8 (B, CH₂), 37.5 (d, J )

21, B, CH), 36.8 (A, CH₂), 36.7 (d, J ) 21, A, CH), 36.5 (B,

CH₂), 36.3 (d, J ) 3, A, CH₂), 35.9 (d, J ) 27, A, CH), 35.5 (d,

J ) 5, A, CH₂), 35.4 (B, CH₂), 33.6 (d, J ) 27, B, CH), 17.7 (d,

J ) 10, B, Me), 17.3 (d, J ) 11, A, Me), 16.1 (d, J ) 8, A, Me),

15.5 (B, Me), 15.0 (d, J ) 5, B, Me), 14.8 (A, Me), 14.7 (d, J )

18, B, Me), 14.2 (A, Me). ³¹P{¹H} NMR (CDCl₃): δ 74.8 (d, J

) 24, A), 73.8 (d, J ) 25, B), 69.0 (d, J ) 24, A), 68.6 (d, J )

25, B). IR: 3047, 2926, 2864, 1559, 1451, 1424, 1243, 1218,

1170, 1115, 1054, 1019, 753, 715, 698, 643, 545, 455. Anal.

Calcd for C₂₅H₃₅IOP₂Pd‚0.1CH₂Cl₂: C, 46.01; H, 5.41. Found:

C, 45.94; H, 5.34.

P d ((R,S)-t-Bu -J osip h os)(o-An )(I) (6). A 50 mL ampule

was charged with Pd(TMEDA)(o-An)(I) (9; 250 mg, 0.547

mmol) and (R,S)-t-Bu-J osiphos (297 mg, 0.547 mmol) in 5 mL

of THF. The reaction flask was heated at 50 °C with stirring

under N₂. The reaction was monitored by ³¹P{¹H} NMR. After

24 h, the orange product precipitated out of solution. It was

collected and washed with petroleum ether. The mother liquor

was pumped dry, fresh THF was added, and heating was

continued. In this manner, the product was periodically

collected until its formation ceased (3 days). Yield: 414 mg

(85%). A sample was purified for elemental and crystal-

lographic analysis by recrystallization from CH₂Cl₂/Et₂O at

-25 °C. Two atropisomers (A and B) were observed by NMR

in a 5:1 ratio.

Sep a r a tion of th e Dia ster eom er s of P d ((S,S)-Ch ir a -

p h os)(o-An )(P (Me)(P h )(BH₃)) (11) a n d Isola tion of P u r e

P d ((S,S)-Ch ir a p h os)(o-An )(S_P-P (Me)(P h )(BH₃)) (11a ). Pd-

((S,S)-Chiraphos)(o-An)(I) (4; 300 mg, 0.391 mmol) was sus-

pended in toluene (4 mL) with vigorous stirring, and rac-

PH(Me)(Ph)(BH₃) (2, 54 mg, 0.39 mmol) was added as a

3218 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

solution in toluene (2 mL). NaOSiMe₃(0.371 mL, 1.0 M

solution in THF, 0.37 mmol) was then added slowly by syringe.

The mixture became somewhat darker, and the slurry was

stirred for 30 min at room temperature and then filtered

through Celite to remove NaI. The Celite was washed with

several portions of toluene (total 5 mL), giving a golden yellow

solution. (Exhaustive extraction of the Celite/solid is necessary

to ensure complete extraction of all of the less soluble diaste-

reomer.) Removal of all volatiles in vacuo left a sticky orange

solid, to which Et₂O (5 mL) was added with vigorous stirring,

causing a white solid to precipitate. The mixture was stirred

for 10 min, and then the white solid was isolated by filtration

on a frit, washed with Et₂O (3 mL), and dried in vacuo. NMR

spectroscopy revealed this solid to be highly enriched in 11a

and its atropisomer 11d (typically greater than 90% de), and

it was found to be analytically pure. The Et₂O-soluble fraction

was pumped down to give a sticky orange solid. NMR analysis

of this material showed it contained mainly 11b but also

significant quantities of siloxy-containing byproducts. Typical

yield of 11a : 100 mg (33%, 0.131 mmol). Crystals that were

suitable for X-ray analysis were obtained by slow (11 months)

diffusion of petroleum ether into a concentrated THF solution

of diastereomerically pure 11a at -25 °C.

Anal. Calcd for C₄₂H₄₆P₃BOPd: C, 64.93; H, 5.97. Found:

C, 64.60; H, 5.78. ¹H NMR (THF-d₈): δ 8.12-8.08 (m, 2H, Ar),

7.95-7.91 (m, 2H, Ar), 7.63-7.50 (m, 6H, Ar), 7.35-7.17 (m,

7H, Ar), 7.15-7.11 (m, 2H, Ar), 6.83-6.82 (m, 1H, Ar), 6.77-

6.72 (m, 3H, Ar), 6.70-6.64 (m, 4H, Ar), 6.48-6.45 (m, 1H,

Ar), 6.21-6.18 (m, 1H, Ar), 3.23 (OMe), 2.12-2.01 (m, 2H, CH),

0.93-0.87 (m, 6H, Chiraphos Me), 0.44 (dd, J _PH) 9, 2, 3H,

P-Me). ¹³C{¹H} NMR (CD₂Cl₂): δ 161.6 (Ar), 150.0 (Ar), 149.2

(Ar), 143.1 (d, J ) 26, Ar), 137.8-137.7 (m, Ar), 137.6 (d, J )

13, Ar), 137.4 (d, J ) 13, Ar), 134.4-134.3 (m, Ar), 132.8 (d, J

) 10, Ar), 132.2 (d, J ) 2, Ar), 132.1-132.0 (m, Ar), 131.9 (Ar),

129.3 (d, J ) 11, Ar), 129.2 (Ar), 128.9 (d, J ) 9, Ar), 128.8 (d,

J ) 10, Ar), 128.5 (d, J ) 9, Ar), 128.2 (Ar), 127.9 (Ar), 127.6-

127.5 (m, Ar), 127.3 (Ar), 127.0 (d, J ) 8, Ar), 124.3 (Ar), 120.5

(d, J ) 7, Ar), 109.8 (Ar), 54.7 (OMe), 38.5-38.2 (m, CH), 33.6-

33.3 (m, CH), 16.7 (d, J ) 24, P-Me), 14.6-14.4 (m, Chiraphos

Me), 14.0-13.8 (m, Chiraphos Me). ³¹P{¹H} NMR (THF-d₈):

δ 52.1 (dd, J ) 291, 38), 50.9 (dd, J ) 38, 16), 7.0 (broad d, J

) 291). FAB-MS (Magic Bullet): m/z 775 (M - H)⁺, 762, 685,

655, 532 [Pd(Chiraphos)]⁺, 476, 455, 398, 371, 309, 291, 263,

243, 195, 155, 135, 119.

purple solution was layered with petroleum ether (10 mL) and

stored at -25 °C for 24 h. A pale pink solid was isolated by

decantation, washed with petroleum ether (2 mL), and dried

in vacuo. H NMR spectroscopy revealed this solid to contain

11b (and its atropisomer 11c) with de >99%. Yield: 175 mg

(0.229 mmol, 70%).

1

Crystals that were suitable for X-ray analysis were obtained

from ether at -25 °C. After the structure of 11b was deter-

mined by X-ray crystallography, the single crystal used for the

structure determination was dissolved in THF-d₈and its ¹H

NMR spectrum was obtained, to correlate the NMR data for

11a and 11b with their absolute configurations.

Anal. Calcd for C₄₂H₄₆P₃BOPd: C, 64.93; H, 5.97. Found:

C, 64.58; H, 5.83. ¹H NMR (THF-d₈): δ 8.34-8.30 (m, 2H, Ar),

7.82-7.79 (m, 2H, Ar), 7.63-7.45 (m, 8H, Ar), 7.35-7.32 (m,

1H, Ar), 7.26-7.17 (m, 5H, Ar), 7.13-7.05 (m, 3H, Ar), 6.91-

6.88 (m, 1H, Ar), 6.84-6.81 (m, 2H, Ar), 6.67-6.65 (m, 3H,

Ar), 6.46-6.43 (m, 1H, Ar), 6.00-5.97 (m, 1H, Ar), 3.11 (OMe),

2.11-2.05 (m, 1H, CH), 1.98-1.94 (m, 1H, CH), 0.98 (dd, J )

10, 7, 3H, Me), 0.90 (dd, J ) 10, 7, 3H, Me), 0.59 (dd, J _PH) 8,

3, P-Me). ³¹P{¹H} NMR (THF-d₈): δ 54.3 (dd, J ) 287, 36),

49.5 (dd, J ) 36, 27), -9.1 (broad d, J ) 287).

Purified samples of 11b, and those formed in situ by reaction

of 4 with 2, contained small amounts of atropisomer 11c, which

was identified by ³¹P{¹H} NMR and ¹H NMR. The 11b:11c

ratio was consistently ca. 30:1 in isolated samples but varied

from ca. 10:1 to 20:1 in the crude material, depending on

reaction conditions for the transmetalation. Data for 11c are

as follows. ³¹P{¹H} NMR (THF-d₈): δ 47.2 (dd, J ) 292, 37),

1

45.1 (dd, J ) 37, 27), -5.0 (br d, J ) 292). H NMR (THF-d₈):

δ 3.41 (OMe), 1.33-1.28 (m, Me), 0.44 (dd, J _PH) 8, 3, PMe).

Kin etic Resolu tion . Syn th esis of 11a . Pd((S,S)-Chira-

phos)(o-An)(I) (4; 139 mg, 0.181 mmol) was weighed into a vial

and slurried in toluene (2 mL), and a solution of rac-PH(Me)-

(Ph)(BH₃) (2; 50 mg, 0.36 mmol, 2 equiv) in toluene (2 mL)

was added. NaOSiMe₃(181 µL, 1.0 M solution in THF, 0.18

mmol) was then added via microliter syringe and the yellow

slurry stirred for 30 min at room temperature. All volatiles

were removed in vacuo to leave a sticky pale yellow residue.

¹H NMR spectroscopic analysis of this solid (THF-d₈) indicated

the ratio of diastereomers (and accompanying atropisomers)

of Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH₃)) 11a :11b ) 5.84:

1, giving an overall de of 70% (the same result was obtained

in a second run). The resultant solid was extracted with Et₂O

(10 mL), and the yellow extracts were pumped down to give a

sticky yellow solid, containing 11b, PH(Me)(Ph)(BH₃), and

siloxy-containing impurities. The residual PH(Me)(Ph)(BH₃)

was isolated by chromatography of this solid on silica gel with

1:1 hexane/CH₂Cl₂as eluent. Chiral HPLC analysis (Chiralcel

OJ -H) of the isolated PH(Me)(Ph)(BH₃) showed it to be

enriched in (S_P)-PH(Me)(Ph)(BH₃) with an ee of approximately

30%.

Purified samples of 11a , and those formed in situ by reaction

of 4 with 2, contained small amounts of atropisomer 11d ,

1

which was identified by ³¹P{¹H} NMR and H NMR. The 11a :

11d ratio ranged from ca. 10:1 to 40:1 and seemed to depend

on conditions. Data for 11d are as follows. ³¹P{¹H} NMR (THF-

d₈): δ 48.4 (dd, J ) 292, 36), 45.5 (dd, J ) 36, obscured by

signals of 11a , so that the other coupling could not be

1

measured), -12.6 (br d, J ) 292). H NMR (THF-d₈): δ 3.29

(OMe), 0.67 (dd, J _PH) 8, 4, PMe).

The Et₂O-insoluble material was dissolved in toluene (total

15 mL), and the solution was filtered and reduced in volume

to ca. 4 mL, at which point white solid started to precipitate.

The solution was layered with pentane (10 mL) and stored at

-25 °C for 3 days to yield 111 mg (0.145 mmol, 80% yield) of

Pd((S,S)-Chiraphos)(o-An)((S_P)-P(Me)(Ph)(BH₃)) (11a ) with

Dia ster eoselective Syn th esis of P d ((S,S)-Ch ir a p h os)-

(o-An )((R_P)-P (Me)(P h )(BH₃)) (11b). Pd((S,S)-Chiraphos)(o-

An)(I) (4; 250 mg, 0.326 mmol) and (S_P)-PH(Me)(Ph)(BH₃) (2;

45 mg, 0.33 mmol) were weighed in the glovebox and trans-

ferred to a Schlenk flask with THF (total 5 mL). The flask

was removed from the glovebox and cooled to -78 °C, and

NaOSiMe₃(0.326 mL, 1.0 M solution in THF, 0.33 mmol) was

added by syringe under N₂. The mixture was stirred at -78

°C for 2 h, and then the cold bath was removed and the

mixture warmed to room temperature. All volatiles were then

removed in vacuo to yield a pale orange sticky solid, which

darkened over time. The residue was washed with Et₂O (5 mL)

and the washings stripped in vacuo to give a sticky red solid.

¹H NMR (THF-d₈) analysis of the solid revealed small amounts

of 11b and 11a (in approximate ratio 92:8) and large quantities

of a OSiMe₃-containing impurity. The Et₂O-insoluble material

was then extracted with toluene (total 15 mL), filtered through

Celite, and reduced in volume to ca. 3 mL in vacuo. The brown-

1

>99% de (as shown by H NMR in THF-d₈).

P d ((R,R)-Me-Du p h os)(o-An )(P (Me)(P h )(BH₃)) (12a ,b).

Meth od 1. To a stirred solution of Pd((R,R)-Me-Duphos)(o-

An)(I) (5; 50 mg, 0.077 mmol) in THF (8 mL) were added PH-

(Me)(Ph)(BH₃) (11 mg, 0.077 mmol) and NaOSiMe₃(77 µL of

a 1.0 M THF solution, 0.077 mmol). The mixture was stirred

for 10 min and concentrated to 1 mL by removal of the solvent

in vacuo. The ³¹P{¹H} NMR spectrum of this crude reaction

mixture showed four species: two major diastereomers (12a ,

12b) in a 1:1 ratio and two minor rotamers (12c, 12d ) in a 2:1

ratio. This reaction mixture was characterized by ³¹P{¹H}

COSY NMR spectroscopy. ³¹P{¹H} NMR (THF with a DMSO-

d₆insert): δ 73.1 (dd, J ) 31, 26, 12a ), 71.4 (dd, J ) 287, 26,

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3219

12a ), 70.4 (dd, J ) 310, 27, 12b), 70.0 (apparent t, J ) 27,

12b), 69.6 (apparent t, J ) 27, 12c), 69.0 (dd, J ) 26, 25, 12d ),

67.4 (dd, J ) 297, 25, 12d ), 67.1 (dd, J ) 298, 26, 12c), -9.6

(broad d, J ) 310, 12b), -14.5 (broad d, J ) 298, 12c), -20.2

(broad d, J ) 287, 12a ). Note that the phosphido-borane

resonance for 12d was not observed.

2.30 (m, 2H, CH), 1.06 (dd, J _PH) 4, J _HH) 8, 6H, Me). ³¹P{¹H}

NMR (CDCl₃): δ 60.0. Anal. Calcd for C₂₈H₂₈I₂P₂Pd‚0.8CH₂-

Cl₂: C, 40.48; H, 3.49. Found: C, 40.08; H, 3.26. The presence

of solvent was quantitatively confirmed by H NMR spectros-

copy.

1

P d ((R,R)-Me-Du p h os)Cl₂(19). This complex was prepared

previously by a different method.⁴⁷To a stirred yellow slurry

of Pd(COD)Cl₂(200 mg, 0.70 mmol) in CH₂Cl₂(2 mL) was

added a solution of (R,R)-Me-Duphos (214 mg, 0.70 mmol) in

CH₂Cl₂(1 mL). The reaction mixture was stirred for 1 h, and

a white solid precipitated. The solid was collected on a fine

frit and washed with ether (3 × 5 mL) to yield analytically

pure product (287 mg, 85%).

Meth od 2. To a stirred slurry of Pd((R,R)-Me-Duphos)(o-

An)(I) (10; 200 mg, 0.31 mmol) in toluene (4 mL) were added

PH(Me)(Ph)(BH₃) (43 mg, 0.31 mmol) and NaOSiMe₃(309 µL

of a 1.0 M THF solution, 0.309 mmol). The mixture became

homogeneous, and then a white solid precipitated. The solvent

was removed in vacuo, and the residue was redissolved in

minimal THF and cooled at -25 °C for 2 weeks. The white

precipitate was washed with minimal THF (which caused a

small amount of dissolution) followed by a generous wash with

petroleum ether and dried in vacuo (yield: ca. 40 mg, 20%

yield). This product was shown to be a single diastereomer

(12a ) by ³¹P{¹H} NMR spectroscopy. A second, minor, isomer

was observed in the ¹H NMR spectrum, but it was unclear

whether this was 12b or a rotational conformer. Only the

easily assigned OMe signal is reported here; integrals of this

peak with that of 12a showed an 18:1 ratio. ¹H NMR (CD₂-

Cl₂): δ 7.69-7.66 (m, 1H, Ar), 7.61-7.53 (m, 6H, Ar), 7.20-

7.17 (m, 2H, Ar), 7.15-7.11 (m, 1H, Ar), 6.99-6.96 (m, 1H,

Ar), 6.79-6.76 (m, 1H, Ar), 6.54-6.52 (m, 1H, Ar), 3.63 (OMe,

minor), 3.59 (3H, OMe), 2.51-2.33 (m, 3H, CH₂+ CH), 2.14-

2.05 (m, 1H, CH), 1.96-1.85 (m, 2H, CH₂), 1.79-1.69 (m, 3H,

¹H NMR (CDCl₃): δ 7.75-7.65 (m, 4H, Ar), 3.75-3.62 (m,

2H, CH), 2.71-2.22 (m, 8H, CH₂), 1.82-1.69 (m, 2H, CH), 1.62

(dd, J _PH) 7, J _HH) 9, 6H, Me), 0.95 (dd, J _PH) 7, J _HH) 17,

6H, Me). ³¹P{¹H} NMR (CDCl₃): δ 96.2. Anal. Calcd for C₁₈H₂₈

-

Cl₂P₂Pd‚0.9CH₂Cl₂: C, 40.53; H, 5.36. Found: C, 40.89; H,

5.26. The presence of solvent was confirmed quantitatively by

¹H NMR spectroscopy.

P d ((R,R)-Me-Du p h os)I₂(16). To a stirred solution of Pd-

((R,R)-Me-Duphos)Cl₂(19; 200 mg, 0.41 mmol) in acetone (5

mL) was added a slurry of NaI (248 mg, 1.65 mmol, 4 equiv)

in acetone (3 mL). A yellow solid immediately precipitated,

and the acetone was removed in vacuo. Distilled water (7 mL)

was added, and the yellow product was collected on a fine frit,

washed with water (3 × 10 mL), and dried on the frit to yield

210 mg (75%). A sample was recrystallized from CH₂Cl₂/diethyl

ether for elemental and crystallographic analysis.

¹H NMR (CDCl₃): δ 7.74 (broad, 4H, Ar), 4.24-4.12 (m, 2H,

CH), 2.59-2.14 (m, 8H, CH₂), 1.96-1.85 (m, 2H, CH), 1.56 (dd,

J _PH) 6, J _HH) 20, 6H, Me), 0.91 (dd, J _PH) 7, J _HH) 16, 6H,

Me). ³¹P{¹H} NMR (CDCl₃): δ 95.1. Anal. Calcd for C₁₈H₂₈I₂P₂-

Pd: C, 32.43; H, 4.23. Found: C, 32.55; H, 4.49.

CH₂+ CH), 1.61-1.51 (m, 1H, CH), 1.41 (dd, J _PH) 18, J _HH

)

7, 3H, Me), 1.15 (dd, J _PH) 19, J _HH) 7, 3H, Me), 1.04 (dd, J _PH

) 15, J _HH) 7, 3H, Me), 0.89 (dd, J _PH) 15, J _HH) 7, 3H, Me),

0.85 (dd, J _PH) 9, 3, 3H, P-Me), 0.69-0.57 (m, 2H, CH₂). ¹³C-

{¹H} NMR (CD₂Cl₂): δ 161.8 (Ar, quat), 149.0 (d, J ) 106, Ar,

quat), 145.9 (ddd, J ) 39, 28, 3, Ar, quat), 144.9 (dm, J ) 24,

Ar, quat), 142.6 (ddd, J ) 38, 27, 3, Ar, quat), 139.8 (Ar, CH),

133.9 (d, J ) 15, Ar, CH), 133.15 (d, J ) 8, Ar, CH), 133.14 (d,

J ) 8, Ar, CH), 133.1 (Ar, CH), 131.2 (m, Ar, CH), 130.8 (m,

Ar, CH), 127.3 (d, J ) 8, Ar, CH), 124.6 (Ar, CH), 120.1 (d, J

) 7, Ar, CH), 109.2 (Ar, CH), 54.5 (OMe), 45.1 (d, J ) 22, CH),

44.9 (d, J ) 26, CH), 37.7 (CH₂), 37.3 (CH₂), 35.7 (d, J ) 4,

CH₂), 35.2 (d, J ) 18, CH), 34.8 (d, J ) 4, CH₂), 34.78 (d, J )

22, CH), 16.6 (d, J ) 12, Me), 15.7 (d, J ) 9, Me), 15.1 (d, J )

25, P-Me), 14.3 (d, J ) 2, Me), 14.2 (d, J ) 2, Me). ³¹P{¹H}

NMR (CD₂Cl₂): δ 65.0 (dd, J ) 314, 27), 64.5 (apparent t, J )

26), -20.1 (br d, J ) 314). Anal. Calcd for C₃₂H₄₆BOP₃Pd: C,

58.51; H, 7.06. Found: C, 57.62; H, 7.48.

P d ((S,S)-Ch ir a p h os)₂(15). This complex was synthesized

previously by a different method.³²To a vigorously stirred

slurry of Pd((S,S)-Chiraphos)Cl₂(18; 200 mg, 0.33 mmol) and

(S,S)-Chiraphos (134 mg, 0.31 mmol, 0.95 equiv) in degassed

ethanol (15 mL) was added a solution of NaBH₄(50 mg, 1.3

mmol, 4 equiv) in degassed, distilled H₂O. The reaction

mixture immediately turned bright yellow and was stirred for

45 min. The product was fully precipitated by cooling to 0 °C

and was filtered by cannula. The air-sensitive yellow solid was

washed with degassed water (3 × 10 mL) and left under a flow

of N₂for several days to dry before being brought into the

drybox. The yellow solid was dissolved in THF (2 mL), and

the solution was filtered through Celite. The THF was removed

in vacuo, and the residue was extracted with Et₂O, concen-

trated, and placed in the refrigerator at -25 °C to precipitate

analytically pure yellow crystals (140 mg, 46% yield).

¹H NMR (C₆D₆): δ 7.68 (br, 8H, Ar), 7.37 (br, 8H, Ar), 7.14-

7.11 (m, 4H, Ar), 7.05 (m, 8H, Ar), 6.91-6.88 (m, 12H, Ar),

1.88 (br, 4H, CH), 0.78 (12H, Me). ¹³C{¹H} NMR (C₆D₆): δ

140.5-140.3 (m, Ar), 136.5-136.4 (m, Ar), 136.2-136.0 (m,

Ar), 131.6-131.5 (m, Ar), 128.9 (m, Ar), 128.6 (Ar, CH), 127.4

(m, Ar), 126.7 (Ar, CH), 38.8-38.3 (m, CH), 15.9-15.7 (m, Me).

³¹P{¹H} NMR (C₆D₆): δ 43.8. Anal. Calcd for C₅₆H₅₆P₄Pd‚

0.35Et₂O: C, 69.97; H, 6.09. Found: C, 69.86; H, 6.55. The

P d ((S,S)-Ch ir a p h os)Cl₂(18). This compound was previ-

ously synthesized by a different method.⁴⁶To a stirred slurry

of Pd(COD)Cl₂(150 mg, 0.52 mmol) in CH₂Cl₂(2 mL) was

added a solution of (S,S)-Chiraphos (224 mg, 0.52 mmol) in

CH₂Cl₂. The mixture became homogeneous, and then a white

solid precipitated. The reaction mixture was stirred for 25 min.

The solid was collected on a fine frit, rinsed with diethyl ether,

and dried on the frit to yield 240 mg of product. The ether

was added to the CH₂Cl₂mother liquor to yield a second crop

of product (35 mg, total yield: 275 mg, 87%). ³¹P{¹H} NMR

(CDCl₃): δ 66.6.

P d ((S,S)-Ch ir a p h os)I₂(13). To a clear, colorless, stirred

solution of Pd((S,S)-Chiraphos)Cl₂(18; 56 mg, 0.17 mmol) in

acetone (3 mL) was added a slurry of NaI (56 mg, 0.66 mmol,

4 equiv) in acetone (2 mL). The reaction mixture turned bright

yellow and was stirred for 1 h. The acetone was removed in

vacuo, and distilled water (7 mL) was added. The yellow

product was collected on a fine frit, washed three times with

water (10 mL), and dried on the frit to yield 50 mg (83%). A

sample was recrystallized from CH₂Cl₂for elemental and

crystallographic analysis.

1

presence of solvent was quantitatively confirmed by H NMR

spectroscopy.

P d ((R,R)-Me-Du p h os)₂(17). To a vigorously stirred slurry

of Pd((R,R)-Me-Duphos)Cl₂(19; 200 mg, 0.41 mmol) and (R,R)-

Me-Duphos (120 mg, 0.39 mmol, 0.95 equiv) in degassed

ethanol (15 mL) was added a solution of NaBH₄(62 mg, 1.6

mmol, 4 equiv) in degassed H₂O. The reaction mixture im-

mediately turned bright orange and was stirred for 20 min.

The product was fully precipitated by cooling to 0 °C and was

filtered by cannula. The air-sensitive orange solid was washed

with degassed water (3 × 10 mL) and dried under a stream of

¹H NMR (CDCl₃): δ 8.02-7.98 (m, 4H, Ar), 7.77-7.73 (m,

4H, Ar), 7.69-7.66 (m, 2H, Ar), 7.58-7.49 (m, 10H, Ar), 2.32-

(46) Morandini, F.; Consiglio, G.; Piccolo, O. Inorg. Chim. Acta 1982,

57, 15-19.

(47) Drago, D.; Pregosin, P. S. Organometallics 2002, 21, 1208-1215.

3220 Organometallics, Vol. 22, No. 16, 2003

Moncarz et al.

N₂for several days before being brought into the drybox.

Recrystallization from petroleum ether at -25 °C yielded 210

mg (71% yield) of orange crystals. Analytically pure material

was obtained after a second recrystallization from petroleum

ether at -25 °C.

Binap)(o-An)(I) (7; 74 mg, 0.07 mmol) and (R)-Tol-Binap (49

mg, 0.07 mmol) in THF (2 mL) was transferred a solution of

PH(Me)(Ph)(BH₃) (10 mg, 0.07 mmol) and NaOSiMe₃(73 mL

of 1.0 M solution in THF, 0.073 mmol) in THF (1 mL). The

mixture turned bright red and then dark purple. ³¹P{¹H} NMR

(THF): δ 24.1 (Pd((R)-Tol-Binap)₂), 9.2 (br, PAMP-BH₃),

-16.5.

¹H{³¹P} NMR (C₆D₆): δ 7.62-7.60 (m, 4H, Ar), 7.14-7.12

(m, 4H, Ar), 2.60-2.52 (m, 4H, CH), 2.33-2.24 (m, 8H, CH,

CH₂), 2.00-1.93 (m, 4H, CH₂), 1.69-1.61 (m, 4H, CH₂), 1.56-

Rea ction of P d (d p p e)(o-An )(I) (3), P H(Me)(P h )(BH₃),

a n d Na OSiMe₃. To a solution of Pd(dppe)(o-An)(I) (3; 20 mg,

0.027 mmol) in THF (1.75 mL) was added enantioenriched PH-

(Me)(Ph)(BH₃) (2; 6.0 µL, 0.027 mmol, about 75% ee (R_P)) and

o-AnI (3.4 µL, 0.027 mmol), to give a pale yellow solution.

NaOSiMe₃(27 µL of a 1.0 M solution in THF, 0.027 mmol)

was added. The solution briefly became salmon colored and

upon mixing turned a light orange-yellow. THF-d₈(about 5

drops) was added to enable NMR locking. The reaction was

monitored by ³¹P NMR after 30 min, which showed that Pd-

(dppe)(o-An)(P(Me)(Ph)(BH₃)) (10) was formed as a 1:1 mixture

of atropisomers: δ 44.795 (dd, J ) 293.01, 22.87), 42.710 (dd,

J ) 300.70, 22.87), 42.318 (overlapped dd, J ) 27.70, 24.38),

41.922 (dd, J ) 27.52, 22.87), -2.4 (broad d, J ≈ 290), -14.9

(broad d, J ≈ 300). The reductive elimination product Pd-

(dppe)₂(δ 31.3) was also observed; over 48 h further decom-

position gave more of this product as well as 1, 3, and in some

cases Pd(dppe)I₂(see the text for more details). Similar results

were observed with racemic 2.

1.48 (m, 4H, CH₂), 1.32 (d, J _HH) 8, 12H, Me), 0.85 (d, J _HH

)

6, 12H, Me). ¹³C{¹H} NMR (C₆D₆): δ 149.8-149.2 (m, Ar),

132.2 (Ar), 127.6 (d, J ) 7, Ar), 42.2-42.0 (m, CH), 37.3 (CH₂),

37.0-36.9 (m, CH), 36.8 (CH₂), 22.8-22.5 (m, Me), 15.5 (m,

Me). ³¹P{¹H} NMR (C₆D₆): δ 57.5. Anal. Calcd for C₃₆H₅₆P₄-

Pd: C, 60.13; H, 7.85. Found: C, 59.76; H, 8.12.

Gen er a l P r oced u r e for Ca ta lysis w ith P d ((R,S)-t-Bu -

J osip h os)(o-An )(I) (6). Meth od 1. Pd((R,S)-t-Bu-J osiphos)-

(o-An)(I) (6; 5 mg, 0.006 mmol, 0.04 equiv) was weighed into

a vial in the glovebox and dissolved in THF (0.5 mL), and o-AnI

(38 µL, 0.29 mmol) and PH(Me)(Ph)(BH₃) (20 mg, 0.14 mmol)

were added to the solution. Proton Sponge (31 mg, 0.15 mmol)

was dissolved in THF (0.5 mL), and this solution was added

to the catalyst solution. The mixture was then transferred to

an NMR tube, the vials were rinsed with a further small

amount of THF, and the washings were added to the tube.

The mixture was allowed to stand at room temperature or

placed in an oil bath at 40 °C, during which time it slowly

deposited large colorless crystals of protonated Proton Sponge

(according to ¹H NMR after isolation). The reaction was

monitored by ³¹P NMR spectroscopy every 24 h. When the ratio

of product to starting material (as determined by integration

of the signals in the ³¹P spectrum) was approximately 45:55,

no further reaction occurred. The NMR tube was returned to

the glovebox, a second equivalent of base was added, and the

tube was returned to the oil bath (if required). The reaction

was then found to proceed smoothly to a ratio of approximately

90:10 product to starting material. The contents of the NMR

tube were then filtered and the solids washed with THF (ca.

2 mL). The filtrate and washings were pumped to dryness in

vacuo, and the residue was purified by column chromatography

on silica gel (acid washed, 230-400 mesh), with 2:1 hexanes/

ethyl acetate as eluent (PAMP-BH₃R_f) 0.64). The product

was isolated as a pale yellow solid and its identity confirmed

by ¹H and ³¹P NMR spectroscopy (CDCl₃). Further purification

was achieved by recrystallization from hexanes/CH₂Cl₂at -60

°C. The ee was determined by chiral HPLC (Chiralpak AD,

1% i-PrOH/hexane, flow rate 1 mL/min; retention times are

11.8 (S) and 13.4 min (R)). Retention times were compared to

those of the racemate and authentic (R_P)-PAMP-BH₃(pre-

pared by the method of Livinghouse) run under identical

conditions.²ⁱ

Met h od 2. An NMR tube was prepared as in method 1.

NaOSiMe₃(6 µL, 1.0 M solution in THF, 6 µmol) was then

added to the tube via microliter syringe. The mixture was

allowed to stand at room temperature or placed in an oil bath

at 40 °C, during which time it slowly deposited large colorless

crystals of protonated Proton Sponge (¹H NMR); formation of

unidentified bubbles also occurred. The reaction was monitored

by ³¹P NMR spectroscopy every 24 h; although the rate slowed

over time, it was not necessary to add more base. Workup and

ee assay were performed as described in Method 1.

Stoich iom etr ic Rea ction of P d ((R,S)-t-Bu -J osip h os)-

(o-An )(I) (6), P H(Me)(P h )(BH₃), Na OSiMe₃, a n d o-An I. To

a solution of Pd((R,S)-t-Bu-J osiphos)(o-An)(I) (6; 128 mg, 0.15

mmol) in THF (10 mL) was added o-AnI (38 µL, 0.29 mmol, 2

equiv), PH(Me)(Ph)(BH₃) (20 mg, 0.15 mmol), and then NaO-

SiMe₃(145 µL of a 1.0 M solution in THF, 0.145 mmol). The

mixture was stirred for 1 h, and the ³¹P{¹H} NMR spectrum

showed signals for PAMP-BH₃, a small amount of PAMP, the

two atropisomers of 6, and its regioisomer (see Table 1).

Rea ction of P d ((R)-Tol-Bin a p )(o-An )(I) (7), P H(Me)-

(P h )(BH₃), a n d Na OSiMe₃. To a solution of Pd((R)-Tol-

Gen er a l P r oced u r e for Tr a n sm eta la tion Exp er im en ts

w ith Ch ir a p h os Com p lex 4. In the glovebox, Pd((S,S)-

Chiraphos)(o-An)(I) (4; 28 mg, 0.037 mmol) was transferred

to an NMR tube as a slurry in THF-d₈(1 mL) along with a

solution of (S_P)-PH(Me)(Ph)(BH₃) (2; 5 mg, 0.036 mmol) of

known ee in THF-d₈(0.5 mL). The tube was fitted with a

rubber septum and cooled to -78 °C in a dry ice/acetone bath.

NaOSiMe₃(36.2 µL, 1.0 M solution in THF, 0.036 mmol) was

then added by microliter syringe. After 1 min, the tube was

inverted to ensure complete mixing; the tube was kept in the

bath for a further 15 min and inverted every 5 min. It was

1

then warmed to room temperature, and the H and ³¹P NMR

spectra were recorded. The de of the product was calculated

from integration of the OMe signals of both diastereomers and

their respective atropisomers in the ¹H NMR spectrum.

Alk yla tion of P H(Me)(P h )(BH₃) (2) w ith p-Meth oxy-

ben zyl Ch lor id e. n-BuLi (986 µL of a 1.6 M solution in

hexanes, 1.58 mmol) was added dropwise to a solution of rac-

PH(Me)(Ph)(BH₃) (200 mg, 1.45 mmol) and HMPA (492 µL)

in dry THF (2 mL) at -78 °C. The resultant yellow solution

was stirred for 15 min at -78 °C, and then 4-methoxybenzyl

chloride (214 µL, 1.58 mmol) was added by syringe. The

solution was stirred for a further 3 h at -78 °C and then

warmed to room temperature and stirred overnight. Water (3

mL) was added, the layers were separated, and the aqueous

layer was extracted with Et₂O (3 × 3 mL). The combined

organic extracts were washed with brine (2 × 3 mL), dried

over MgSO₄, filtered, and pumped to dryness in vacuo. The

crude product was purified by gravity column chromatography

on silica with CH₂Cl₂/hexanes as eluent (2:1, R_f) 0.33),

yielding P(Me)(Ph)(CH₂-p-MeOC₆H₄)(BH₃) (19) as a colorless,

viscous oil that solidified on standing. Yield: 244 mg (0.945

mmol, 65%).

Anal. Calcd for C₁₅H₂₀POB: C, 69.80; H, 7.81. Found: C,

69.84; H, 7.81. ³¹P{¹H} NMR (CDCl₃): δ 11.4 (br q, J _P-B

)

58). ¹H NMR (CDCl₃): δ 7.59-7.40 (m, 5H, Ar), 6.86-6.81 (m,

2H, Ar), 6.78-6.74 (m, 2H, A), 3.78 (3H, OMe), 3.17-3.13 (m,

2H, CH₂), 1.49 (d, J ) 10, 3H, PMe), 1.2-0.2 (v br q, 3H, BH₃).

¹³C{¹H} NMR (CDCl₃): δ 158.8 (d, J ) 2.5, quat Ar), 131.9 (d,

J ) 9, Ar), 131.5 (d, J ) 2, Ar), 130.9 (d, J ) 4, Ar), 129.0 (d,

J ) 53, quat Ar), 128.7 (d, J ) 10, Ar), 113.9 (d, J ) 3, Ar),

124.3 (d, J ) 7, quat Ar), 55.4 (OMe), 35.1 (d, J ) 32, CH₂),

9.0 (d, J ) 39, PMe). HPLC (Chiralpak AD, 3% i-PrOH in

hexanes, flow rate 1 mL min^-1): retention times are 10.4 (S)

and 12.4 (R) min.

Palladium-Catalyzed Asymmetric Phosphination

Organometallics, Vol. 22, No. 16, 2003 3221

Alk yla tion of En a n tioen r ich ed P H(Me)(P h )(BH₃) (2)

w ith p-Meth oxyben zyl Ch lor id e. Highly enantioenriched

(S_P)-PH(Me)(Ph)(BH₃) (60 mg, 0.43 mmol, ee determined by

chiral HPLC) was weighed in the glovebox, dissolved in THF

(1 mL), and transferred to a Schlenk flask. The solution was

cooled to -78 °C, and n-BuLi (296 µL, 1.6 M in hexanes, 0.474

mmol) was added by syringe. A yellow color instantly formed,

and the solution was stirred for 10 min. 4-Methoxybenzyl

chloride (64.3 µL, 0.474 mmol) was then added by microliter

syringe and the mixture stirred at -78 °C for 6 h. The solution

was warmed to room temperature and then quenched with

H₂O (1 mL). The organic layer was separated and the aqueous

layer extracted with Et₂O (3 × 2 mL). The organic extracts

were combined, washed with brine (3 mL), dried over MgSO₄,

and stripped to dryness in vacuo. The crude product (19) was

purified by gravity column chromatography on silica, as

described above. The ee of 19 was determined by chiral HPLC.

Gen er a l P r oced u r e for Red u ctive Elim in a tion Rea c-

tion s w ith Ch ir a p h os Com p lex 11. A solution of highly

diastereomerically enriched Pd((S,S)-Chiraphos)(o-An)(P(Me)-

(Ph)(BH₃)) (typical scale 50 mg) in THF-d₈was transferred to

an NMR tube, along with a solution of FeCp₂(ca. 5 mg) and

diphenylacetylene (4 equiv) in THF-d₈. (Use of a smaller excess

of diphenylacetylene was found to result in lower ee’s and

increased OMe-containing impurities.) Initial ¹H and ³¹P NMR

spectra were recorded, and the initial de (ratio of 11a + 11d

to 11b + 11c) determined by integration of the OMe signals

removed in vacuo. The residue was extracted repeatedly with

toluene (total 10 mL), and the resulting solution was filtered

through Celite and concentrated to ca. 2 mL. This solution was

layered with petroleum ether (5 mL) and cooled to -25 °C for

24 h, after which time a dirty yellow solid was isolated and

dried in vacuo. Isolated yield: 50 mg (0.07 mmol, 39%).

¹H NMR (THF-d₈): δ 7.89-7.75 (m, 8H, Ar), 7.49-7.34 (m,

4H, Ar), 7.31-6.97 (m, 18H, Ar), 2.62 (br, 2H, CH), 0.84 (br,

6H, Me). ¹³C{¹H) NMR (THF-d₈): 137.7-137.4 (m), 136.5

(apparent t, J ) 8), 135.5 (apparent t, J ) 11), 135.1-134.8

(m), 134.0 (apparent t, J ) 7), 131.6 (apparent t, J ) 3), 130.8,

130.0, 129.8, 129.4 (apparent t, J ) 4), 129.1, 128.8 (apparent

t, J ) 5), 128.5, 126.3, 126.2, 124.5, 123.7, 40.2 (apparent t, J

) 21, CH), 17.5 (apparent t, J ) 4, Me). ³¹P{¹H} NMR (THF-

d₈): δ 49.9. IR: 3056, 2956, 2922, 1800, 1644, 1583, 1478, 1433,

1256, 1094, 1022, 800, 750, 689, 528. Anal. Calcd for C₄₂H₃₈P₂-

Pd: C, 70.94; H, 5.39. Found: C, 70.57; H, 5.34.

Cr ysta llogr a p h ic Str u ctu r e Deter m in a tion s. A sum-

mary of the crystallographic data is given in Table 3, with

additional details in the Supporting Information. Structural

data for complexes 11a and 11b were reported previously.¹⁰

The systematic absences in the diffraction data are uniquely

consistent for the reported space group for 5 and 9 and

consistent for the space groups P2₁and P2₁/m for 6 and 4. No

evidence of symmetry higher than triclinic was observed in

the diffraction data of 3. E statistics and the value of Z

suggested the centrosymmetric option of 3, and the absence

of mirror plane symmetry in 6 and 4 precluded the centrosym-

metric option. These choices yielded chemically reasonable and

computationally stable refinements. The structures were

solved using direct methods, completed by subsequent differ-

ence Fourier syntheses, and refined by full-matrix least-

squares procedures. DIFABS⁴⁸absorption correction was

applied to 3-5. Platon/Squeeze⁴⁹was applied to 5 to resolve a

dichloromethane molecule (42 electrons) per Pd complex.

Within the 631.9 Å³void space occupied by solvent molecules

per unit cell, a total of 172 electrons (43 electrons/complex)

was found. In this treatment of solvent, the contribution of

the solvent molecule is treated collectively and is not refined

as individual atoms. Structure 5 is an 87:13 racemic mixture,

and the absolute configurations of 6 and 4 were determined

(Flack parameters are 0.03(3) and 0.01(7), respectively). The

phenyl rings of 3 and 4 were refined as rigid planar groups.

All non-hydrogen atoms were refined with anisotropic dis-

placement coefficients, and all hydrogen atoms were treated

as idealized contributions. All software and sources of the

scattering factors are contained in the SHELXTL (5.10)

program library (G. Sheldrick, Siemens XRD, Madison, WI).

1

in the H NMR spectra; similarly, the initial ratio of Pd (total

OMe signals) to FeCp₂was also determined.

The NMR tube was then placed in an oil bath at 50 °C and

monitored by NMR spectroscopy periodically. A small amount

of solid was seen to deposit during the course of the reaction.

Reactions were typically run for 42 h (11b) and 72 h (11a ),

since the rates of reductive elimination were different for the

two diastereomers. The use of longer reaction times to effect

near-complete conversion generally resulted in the appearance

of extra unidentified signals in the spectra, indicating decom-

position by other pathways. Formation of PAMP-BH₃was

indicated by the appearance of a singlet at 3.67 ppm in the

¹H NMR spectrum (and a quartet at 10.2 ppm in the ³¹P NMR

spectrum) and of Pd((S,S)-Chiraphos)(PhCtCPh) by a singlet

at 49.9 ppm in the ³¹P NMR spectrum (see below). Other

significant byproducts observed in these reactions are detailed

in Table 10.

The reaction mixture was then transferred to a vial in air,

the tube washed with additional THF, and the solvent removed

in vacuo. The residue was extracted with Et₂O in several

portions (total 10 mL), and again the solvent was removed in

vacuo. PAMP-BH₃was then isolated by preparative TLC on

silica, with the residue loaded as a solution in CH₂Cl₂and with

hexanes/ethyl acetate as eluent (2:1). NMR yields of PAMP-

BH₃ranged from 50 to 70%, and isolated yields were typically

20%. The identity of the product was confirmed by ¹H NMR

(CDCl₃or C₆D₆), and the ee was determined by chiral HPLC

(Chiralpak AD, 1% i-PrOH/hexane, flow rate 1 mL/min,

retention times are 11.8 (S) and 13.4 min (R)). Retention times

were compared to those of the racemate and authentic (R_P)-

PAMP-BH₃(prepared by the method of Livinghouse) run

under identical conditions.²ⁱ

Ack n ow led gm en t. We thank the National Science

Foundation, Union Carbide (Innovation Recognition

Program), and DuPont for support. We are grateful to

Professors Tsuneo Imamoto (Chiba University) and Tom

Livinghouse (Montana State University) for advice and

for sharing unpublished results on the preparation of

enantiopure 2 and to Professor J ohn Brown (University

of Oxford) for sharing his related results before publica-

tion.

P d ((S,S)-Ch ir a p h os)(P h CtCP h ) (14). Pd((S,S)-Chira-

phos)Cl₂(18; 110 mg, 0.182 mmol) and diphenylacetylene (65

mg, 0.36 mmol) were stirred as a slurry in dry THF (4 mL),

and a solution of NaBH(OMe)₃(93 mg, 0.73 mmol) in THF (3

mL) was added dropwise. During the addition the reaction

mixture instantly darkened, and at the end of the addition it

was yellow-brown. The mixture was stirred for a further 20

min to give a dark brown slurry, and then all volatiles were

Su p p or tin g In for m a tion Ava ila ble: Details of the X-ray

crystallographic studies. This material is available free of

charge via the Internet at http://pubs.acs.org.

OM030144X

(48) Walker, N.; Stuart, D. Acta Crystallogr., Sect A 1983, 39, 158.

(49) Spek, A. L. Acta Crystallogr., Sect A 1990, 46, C34.

Article Doi

Palladium-catalyzed asymmetric phosphination. Enantioselective synthesis of PAMP-BH3, ligand effects on catalysis, and direct observation of the stereochemistry of transmetalation and reductive elimination

DOI: 10.1021/om030144x

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Article abstract of DOI:10.1021/om030144x

Full text of DOI:10.1021/om030144x

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