P-chirogenic binaphthyl-substituted monophosphines: synthesis and use in enolate vinylation/arylation reactions.

Article abstract of DOI:10.1021/ol025563p

[reaction: see text] New phosphine ligands possessing both axial chirality and a chirogenic phosphorus center were prepared from (R)-2-bromo-2'-N,N-(dimethylamino)-1,1'-binaphthyl (1) via a simple Li-halogen exchange protocol. The asymmetric vinylation of a ketone enolate with (R,R(P))-2-(tert-butylphenylphosphino)-2'-N,N-(dimethylamino)-1,1'-binaphthyl (2a) afforded the coupling product with good enantiomeric excess.

Full text of DOI:10.1021/ol025563p

ORGANIC
LETTERS
2002
Vol. 4, No. 6
999-1001
P-Chirogenic Binaphthyl-Substituted
Monophosphines: Synthesis and Use in
Enolate Vinylation/Arylation Reactions
Takayuki Hamada and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
slbuchwal@mit.edu
Received January 15, 2002
ABSTRACT
New phosphine ligands possessing both axial chirality and a chirogenic phosphorus center were prepared from (R)-2-bromo-2′-N,N-
(dimethylamino)-1,1′-binaphthyl (1) via a simple Li−halogen exchange protocol. The asymmetric vinylation of a ketone enolate with (R,RP)-2-
(tert-butylphenylphosphino)-2′-N,N-(dimethylamino)-1,1′-binaphthyl (2a) afforded the coupling product with good enantiomeric excess.
In the past 3 decades, a large number of chiral phosphines
have been developed,1 and their use as ligands in asymmetric
catalysis has been studied extensively. These chiral ligands
can be divided into three general groups: ligands bearing
axial chirality (e.g., BINAP2 and MOP3); ligands possessing
carbon stereocenters (e.g., DIOP4 and DuPHOS5); and
ligands having chirogenic phosphorus centers (e.g., DI-
PAMP6 and Bis-P*7). Most chiral phosphines typically
possess carbon-based stereogenicity; comparatively few
P-chiral ligands have been reported. Furthermore, ligands
that bear both axial chirality and a chirogenic phosphorus
have not been described.8
Recently, Hayashi has utilized a binaphthyl-substituted
monophosphine ligand (MOP) in asymmetric C-C or C-Si
bond formation reactions.9 Additionally, we reported enan-
tioselective Suzuki couplings10 and enolate vinylations11 and
arylations12 that use (S)-2-dicyclohexylphosphino-2′-N,N-
(dimethylamino)-1,1′-binaphthyl (3) and related phosphines
as the chiral supporting ligand (Figure 1). Since monophos-
phines possessing both axial asymmetry and a stereogenic
phosphorus center have not yet been reported, we sought to
(1) For reviews, see: (a) Noyori R. Asymmetric Catalysis in Organic
Synthesis; John Wiley: New York, 1994. (b) Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH Publishers: Weinheim, 1993.
(2) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345.
(3) (a) Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887. (b)
Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993,
58, 1945. (c) Uozumi, Y.; Suzuki, N.; Ogiwara, A.; Hayashi, T. Tetrahedron
1994, 50, 4293. Kocovsky has reported the dimethylamino-substituted
analogue of MOP (MAP): (d) Kocovsky, P.; Vyskocil, S.; Cisarova, I.;
Sejbal, J.; Tislerova, I.; Smrcina, M.; Lloyd-Jones, G. C.; Stephen, S. C.;
Butts, C. P.; Murray, M.; Langer, V. J. Am. Chem. Soc. 1999, 121, 7714.
(e) Lloyd-Jones, G. C.; Stephen, S. C.; Murray, M.; Butts, C. P.; Vyskocil,
S.; Kocovsky, P. Chem.-Eur. J. 2000, 6, 4348.
(8) For phosphine ligands bearing both carbon and phosphorus stereo-
centers, see: (a) Sprinz, J.; Kiefer, M.; Helmchen, G.; Reggelin, M.; Huttner,
G.; Walter, O.; Zsolnai, L. Tetrahedron Lett. 1994, 35, 1523. (b) Helmchen,
G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336.
(9) (a) Hayashi, T.; Kawatsura, M.; Uozomi, Y. Chem. Commun. 1997,
3561. (b) Hayashi, T. Acc. Chem. Res. 2000, 33, 354. (c) Hayashi, T.;
Ishigedani, M. J. Am. Chem. Soc. 2000, 122, 976. (d) Hayashi, T.; Hirate,
S.; Kitayama, H.; Tsuji, H.; Torii, A.; Uozumi, Y. J. Org. Chem. 2001, 66,
1441 and references therein.
(4) Kagan, H. B.; Dang, T.-P. J. Am. Chem. Soc. 1972, 94, 6429.
(5) Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am.
Chem. Soc. 1993, 115, 10125.
(6) Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L.;
Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946.
(7) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1635.
(10) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12501.
(11) Chieffi, A.; Kamikawa, K.; A° hman, J.; Fox, J. M.; Buchwald, S. L.
Org. Lett. 2001, 3, 1897.
(12) Hamada, T.; Chieffi, A.; A° hman, J.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 1261.
10.1021/ol025563p CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/14/2002

Figure 1. Chiral binaphthyl-substituted monophosphines.
synthesize P-chirogenic binaphthyl monophosphines13 and
test their efficacy in enolate vinylation and arylation pro-
cesses (Figure 1). Furthermore, these ligands may serve as
stereochemical probes to assist us in understanding factors
important to the design of new ligands.
To synthesize 2-(tert-butylphenylphosphino)-2′-(dimethy-
lamino)-1,1′-binaphthyl (2a and 2b), a lithium-halogen
exchange protocol with bromide (R)-110 was used. The
desired diastereomeric products 2a and 2b were formed in
good yield. Recrystallization from Et2O-MeOH (1:2) yielded
2a and 2b in a 4:1 ratio, and an additional recrystallization
from Et2O-MeOH (1:4) provided diastereomerically pure
(R,RP)-(+)-2a in 12% isolated yield (Scheme 1). The absolute
Figure 2. X-ray structure of (R,RP)-2a.
acid14 proceeded very cleanly (Scheme 2), providing (R,SP)-
(+)-2b in 16% overall yield from (R)-1. Similarly, additional
(R,RP)-(-)-2a was obtained in 11% yield from the mother
liquor (23% overall yield of 2a).
Scheme 2. Phosphine-Boranes 4a and 4b: Deprotection
Scheme 1. Synthesis of (R,RP)-2a
An alternative, Pd-based method for the preparation of 2a
and 2b was also explored.3,11 The diastereomeric phosphine
oxides (5a and 5b) could be prepared by the coupling of
(R)-1 and tert-butylphenylphosphine oxide using a Pd/bis-
(diphenylphosphino)butane (DPPB) catalyst (Scheme 3).15
configuration of 2a was determined by X-ray analysis (Figure
2).
Scheme 3. A Pd-Catalyzed C-P Bond Forming Protocol to
Prepare Ligands 2 via Phosphine Oxides 5a and 5b
(R,SP)-2b was isolated in diastereomerically pure form as
well. The mother liquor resulting from the recrystallization
of (R,RP)-2a was stirred with BH3-THF to furnish phos-
phine-boranes 4a and 4b. The diastereomers were separated
by silica gel chromatography. Deprotection of 4b with triflic
(13) Imamoto has recently reported P-chirogenic biphenyl-substituted
ligands: Tsuruta, H.; Imamoto, T. Synlett 2001, 999.
(14) (a) McKinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994, 35, 9319.
(b) McKinstry, L.; Livinghouse, T. Tetrahedron 1995, 51, 7655.
(15) Phosphine oxides 5a and 5b were not obtained in pure form. Thus,
the reported yield is approximate. No attempts optimize this reaction were
made since this route proved unsuccessful.
(16) Schreiber, S. L.; Wang, Z. J. Am. Chem. Soc. 1985, 107, 5303.
(17) Simons, G.; Horner, L. Phosphorus Sulfur Relat. Elem. 1984, 19,
77.
These diastereomeric ligand precursors could be separated
using silica gel chromatography. Unfortunately, epimerization
at phosphorus occurred upon reduction of 5a and 5b using
1000
Org. Lett., Vol. 4, No. 6, 2002

several protocols (e.g., trichlorosilane-R3N,6,16 PhSiH3,17 Ti-
(Oi-Pr)4-PMHS,18 Si2Cl619). Thus, this Pd-based route was
abandoned.
Ligands 2a and 2b were then tested in asymmetric enolate
vinylation11 and arylation12 reactions. Specifically, the cou-
pling of ketone 6 and trans-1-bromopropene or 3-bromo-
toluene in the presence of 2 mol % Pd/2a or Pd/2b were
studied (Table 1). The catalyst using (R,RP)-(+)-2a as ligand
excess (34% ee). In arylations with (R,RP)-(+)-2a or (R,SP)-
(-)-2b, enantioselectivities were very low (5-10% ee). It
should be noted that 3 provided arylation product 7b with
moderate enantioselectivity (58% ee). These results deviate
from a simple double asymmetric scenario where one
diastereomeric configuration results in an improved selectiv-
ity (matched case) and the other results in a diminished
selectivity (mismatched case);20 at present, we have no simple
explanation for these results.
In summary, we have developed a route for the preparation
of P-chirogenic binaphthyl-substituted monophosphines. The
chirogenic phosphine moiety was resolved by use of the
axially chiral binaphthyl backbone; the optical resolution of
2a and 2b was accomplished by fractional crystallization of
the diastereomers. Alternatively, the diastereomeric phos-
phine-boranes could be separated by silica gel chromatog-
raphy. The asymmetric vinylation with Pd/2a furnished the
product with 89% ee. A remarkable difference in the
asymmetric vinylation between 2a and 2b and ligand 3
indicates that the configuration of the phosphorus center plays
an important but complex role in the enantioselectivity-
determining step. We are currently examining these ligands
in the context of other applications in asymmetric catalysis.
Table 1. Ligands 2a, 2b, and 3 in Asymmetric Enolate
Vinylation and Arylation Reactions
Acknowledgment. We wish to thank the National
Institutes of Health (GM 46059). Merck, Pfizer, and Bristol-
Myers Squibb are acknowledged for additional support.We
are grateful to Ajinomoto Co., Inc. for financial support for
T.H. Drs. Joseph M. Fox and Alex R. Muci are acknowl-
edged for helpful discussions and assistance in the prepara-
tion of this manuscript.
a Reaction conditions: 1 mol % Pd2(dba)3, ligand/ Pd ) 1.25/1, 1.0 equiv
ketone, 2.0 equiv R-Br, 2.0 equiv NaOt-Bu, toluene. b Isolated yield by
silica gel column chromatography. c Percent ee determined by HPLC (Daicel
CHIRALCEL OD, hexane/iPrOH ) 9:1, 0.6-1.0 mL/min). d 2 mol %
Pd(OAc)2 used.
Supporting Information Available: Experimental pro-
cedures and characterization data for ligands 2a and 2b and
crystal structure data for 2a. This material is available free
of charge via the Internet at http://pubs.acs.org.
afforded desired vinylation product 7a in 89% ee and 96%
yield, which is similar to the 90% ee observed when
dicyclohexylphosphine-substituted ligand 3 was used. Di-
astereomer (R,SP)-(-)-2b yielded 7a in low enantiomeric
OL025563P
(18) Coumbe, T.; Lawrence, N. J.; Muhammad, F. Tetrahedron Lett.
1994, 35, 625.
(20) For a seminal review on double asymmetric synthesis, see: Masam-
une, S.; Choy, W.; Petersen, J. S.; Sita L. R. Angew. Chem., Int. Ed. Engl.
1985, 24, 1.
(19) Valentine, D., Jr.; Blount, J. F.; Toth, K. J. Org. Chem. 1980, 45,
3691.
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