Chiral silanes via asymmetric hydrosilylation with catalytic CuH

Article abstract of DOI:10.1021/ol0529593

CuH-catalyzed asymmetric conjugate reduction of β-silyl-α, β-unsaturated esters has been developed. Using PMHS as a stoichiometric source of hydride and in situ generated CuH ligated by Solvias' JOSIPHOS analogue PPF-P(t-Bu)₂ leads to highly enantioselective 1,4-reductions.

Full text of DOI:10.1021/ol0529593

ORGANIC
LETTERS
2006
Vol. 8, No. 10
1963-1966
Chiral Silanes via Asymmetric
Hydrosilylation with Catalytic CuH
Bruce H. Lipshutz,* Naoki Tanaka, Benjamin R. Taft, and Ching-Tien Lee
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Barbara, California 93106
lipshutz@chem.ucsb.edu
Received December 6, 2005
ABSTRACT
CuH-catalyzed asymmetric conjugate reduction of
of hydride and in situ generated CuH ligated by Solvias’ JOSIPHOS analogue PPF
â
-silyl-
r
,
â
-unsaturated esters has been developed. Using PMHS as a stoichiometric source
P(t-Bu)2 leads to highly enantioselective 1,4-reductions.
−
Enantioenriched organosilanes are valued intermediates in
organic synthesis.1 Aside from their potential as hydroxyl
surrogates via oxidation under Tamao2/Fleming3 conditions,
they offer many opportunities for asymmetric C-C bond
formations.4 Several routes to chiral silanes are available,4
with the most recent involving a Rh-catalyzed 1,4-addition
of arylboronic acids to, mainly, conjugated enones.5 Ha-
yashi’s (R,R)-Bn-bod ligand (L* in Scheme 1, path A) was
found to give excellent levels of stereoinduction associated
with arylated ketones.5 In this report, we describe an
alternative strategy that allows for the conversion of a broad
array of â-silylated-â,â-disubstituted enoates to chiral silanes
using nonracemically ligated CuH (Scheme 1, path B; PMHS
) polymethylhydrosiloxane).
tions6 of precursor acyl silanes (Scheme 2). Fleming’s PhMe2-
SiLi7 was used to convert a morpholino amide to the
correspondinig acyl silane. HWE on educts 1 (R ) alkyl)
preferentially afforded E-enoates (E-2), whereas an R-tri-
methylsilyl ester anion led to the isomeric Z-species Z-3.
Aryl-substituted educts required 1,2-addition of PhMe2SiLi
to the benzaldehyde and then Swern oxidation to acyl silanes
(1, R ) aromatic).
Asymmetric hydrosilylations of â-silyl enoates E-2 and
Z-3 were conducted with in situ derived CuH, generated
using 1% CuCl and 1% NaOtBu (Method A) or (Ph3P)CuH
(Method B) in the presence of PMHS.8 Solutions contained
1% of a nonracemic ligand, which initially was Takasago’s
R-(-)-DTBM-SEGPHOS (4, Figure 1).9 This combination,
leading to kinetically reactive yet thermodynamically stable
DTBM-SEGPHOS‚CuH,10 has been shown previously to be
extremely selective toward cinnamate-type â,â-disubstituted
Starting materials as pure geometrical isomers were readily
prepared by chromatographic purification following standard
Horner-Wadsworth-Emmons (HWE) or Peterson olefina-
Scheme 1
10.1021/ol0529593 CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/08/2006

1c) the reduction required a longer time (36 vs 9 h) to reach
completion at both a higher temperature (-20 vs -30 °C)
Scheme 2
enoates.11 However, reactions with four different â-silylated
enoates (Table 1, entries 1-4) indicated that this ligand was
not particularly discriminating under these modified circum-
stances. Fortunately, as also observed in our previous study,11
the JOSIPHOS analogue PPF-P(t-Bu)2 (5, Figure 1), sup-
plied by Solvias,12 was very effective as the CuH complex
in delivering hydride to the â-site.
As outlined in Table 1, several Z- (entries 1-3) and E-
(entries 4-9) â-silyl enoates bearing either â-aryl (entries
2, 7, and 8) or â-alkyl (entries 1, 3-6, and 9) substituents
were smoothly reduced in high chemical yields. In general,
we have observed that these substrates are less prone toward
reduction than are nonsilylated enoates,11 requiring longer
reaction times and higher ligand loadings typically run at
0.5 M in toluene. Thus, care needs be exercised to maintain
an inert atmosphere, as adventitious oxygen can destroy the
catalyst over time. Facial selectivity of the CuH complex
derived from (R,S)-PPF-P(t-Bu)2, with a substrate-to-ligand
(S/L) ratio of 100:1, afforded product esters with >90% ee
in most cases. A higher substrate-to-ligand ratio, e.g., 1000:
1, is also possible, although in the one case studied (entry
Figure 1. Nonracemic ligands used in this study.
and a higher concentration (0.7 vs 0.5 M). Although overall
reaction efficiency was maintained (90% isolated yield), the
somewhat higher temperature caused a modest drop in ee
(92% vs 95% ee). The presence of t-BuOH to assist with
catalyst turnover is important as well.13 In the absence of
this additive, a reaction time of 5 h at -30 °C (entry 4c)
took 7 days at room temperature to reach completion. Only
in the case of an especially electron-rich cinnamate 6 (entry
7) did the ee drop, perhaps because of the higher temperature
required to drive the reaction to completion within a 24 h
time period. The E- vs Z- nature of the enoate did not affect
the rate of hydrosilylation (entry 1 vs 4) at related temper-
atures. Although methyl esters appear to be better choices
for otherwise slow-reacting substrates, both ethyl and even
a far more lipophilic ester (e.g., n-octyl, entry 3) react at
similar rates and in good ee’s (compare entries 1 and 3).
Treatment of an E-enoate with enantiomeric [(S,R)-PPF-
P(t-Bu)2]CuH (entry 4b) gave the S-product in an equally
selective event (vs entry 4a).
The enantiomeric excesses and absolute stereochemistry
of each product (other than that for Table 1, entry 9) were
determined by conversion to the known imide derivatives 8
using a commercially available lactam in the form of its
lithium salt, 7 (Scheme 3). Fleming had shown years ago
that de’s of imides 8 could be easily established by NMR,
and assignments of absolute stereochemistry can be made
on the basis of known chemical shifts.14 Thus, initial
saponification of product esters was followed by conversion
(1) (a) Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599. (b) Hiyama,
T.; Shirakawa, E. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; John Wiley & Sons: Hoboken, NJ, 2002; Vol.
1, p 285. (c) Landais, Y.; Chabaud, L.; James, P. Eur. J. Org. Chem. 2004,
15, 3173. (d) Flemng, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97,
2063. (e) Panek, J. S.; Masse, C. E. Chem. ReV. 1995, 95, 1293. (f)
Nishiyama, H. Itoh, K. Asymmetric Hydrosilylation and Related Reactions.
In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley VCH: New York,
2000; Chapter 2. (g) Rendler, S.; Auer, G.; Oestreich, M. Angew. Chem.,
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(2) (a) Tamao, K.; Ishida, N.; Kumada, M. J. Org. Chem. 1983, 48, 2120.
(b) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics 1983,
2, 1694.
(3) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem. Commun.
1984, 29.
(4) (a) Suginome, M.; Ohmura, T.; Miyake, Y.; Mitani, S.; Ito, Y.;
Murakami, M. J. Am. Chem. Soc. 2003, 125, 11174. (b) Hayashi, T.;
Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 5579.
(5) Hayashi, T.; Shintani, R.; Okamoto, K. Org. Lett. 2005, 7, 4757.
(6) Fujiwara, T.; Sawabe, K.; Takeda, T. Tetrahedron 1997, 53, 8349.
(7) (a) Fleming, I.; Newton, T. W.; Roessler, F. J. Chem. Soc., Perkin
Trans. 1981, 2527. (b) Scheidt, K. A.; Clark, C. T.; Milgram, B. C. Org.
Lett. 2004, 6, 3977.
Scheme 3
(8) Lipshutz, B. H.; Noson, K.; Chrisman, W.; Lower, A. J. Am. Chem.
Soc. 2003, 125, 8779.
(9) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264.
(10) Lipshutz, B. H.; Frieman, B. Angew. Chem., Int. Ed. 2005, 44, 6345.
(11) (a) Lipshutz, B. H.; Servesko, J. M.; Taft, B. R. J. Am. Chem. Soc.
2004, 126, 8352. (b) Hughes, G.; Kimura, M.; Buchwald, S. L. J. Am. Chem.
Soc. 2003, 125, 11253.
(12) (a) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062. (b) Blaser, H.-U.; Brieden,
W.; Pugin, B.; Spindler, F.; Studer, M.; Togni, A. Top. Catal. 2002, 19, 3.
1964
Org. Lett., Vol. 8, No. 10, 2006

Table 1. Representative Examples of Asymmetric Hydrosilylations of â-Silyl Enoatesa
a Reactions were run with a S/L ratio of 100:1 with 1.1 equiv of t-BuOH present and at 0.5 M in toluene. The enoates used were geometrically pure
materials. b Fully characterized. c Isolated, chromatographically purified material. d Unless noted otherwise, based on conversion of each product to its chiral
imide derivatives; see text. e Method A (see text). f Method B (see text). g S/L ) 1000:1. h By chiral HPLC.
Org. Lett., Vol. 8, No. 10, 2006
1965

to their acid chlorides. Reaction with the preformed salt 7
gave imides 8. To confirm the method, use of a racemic
â-silyl ester (e.g., Table 1, product in entry 1) led to a 1:1
mix of diastereomers, with the spectral data on each isomer
being in perfect agreement with that of Fleming on these
exact compounds.14 Chiral HPLC analyses were also per-
formed on the products illustrated in entries 7-9, which gave
more precise enantiomeric excesses on baseline-resolved
enantiomers.
In summary, it has been shown that CuH, when complexed
by Solvias’ nonracemic ligand PPF-P(t-Bu)2, can effect
asymmetric hydrosilylation of both â-aryl and â-alkyl â-silyl
enoates in very high enantiomeric excesses. Turnover
numbers of g100 are demonstrated for these highly hindered
substrates, and reaction conditions are quite mild (e0 °C)
and neutral. Both enantiomers of the ligand are readily
available, providing access to either stereochemistry of the
resulting chiral silanes. Finally, use of enoates as substrates
provides a broad range of subsequent opportunities for
functional group interconversions of the product â-silyl
esters,15 where the absolute configuration of the newly
installed residue on silicon should remain intact.
Acknowledgment. We warmly thank the NSF for finan-
cial support. Ligands were generously supplied by Solvias
(H.-U. Blaser and M. Thommen; PPF-P(t-Bu)2) and Takasa-
go (T. Saito and H. Shimizu; DTBM-SEGPHOS). We also
gratefully acknowledge Sankyo Company, Ltd., for support-
ing N.T. while at UCSB.
Supporting Information Available: Procedures and
spectral data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL0529593
(13) (a) Lipshutz, B. H.; Shimizu, H. Angew. Chem., Int. Ed. 2004, 43,
2228. (b) Buchwald, S. L.; Hughes, G.; Kimura, M. J. Am. Chem. Soc.
2003, 125, 11253.
(14) Fleming, I.; Kindon, N. D. J. Chem. Soc., Perkin Trans. 1 1995,
303.
(15) For representative uses of chiral silanes, see: (a) Panek, J. S.; Wrona,
I. E.; Gabarda, A. E.; Evano, G. J. Am. Chem. Soc. 2005, 127, 15026. (b)
Panek, J. S.; Kesavan, S.; Su, Q.; Shao, J.; Porco, J. A., Jr. Org. Lett. 2005,
7, 4435.
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