Ligand-accelerated, copper-catalyzed asymmetric hydrosilylations of aryl ketones

Full text of DOI:10.1021/ja011529e

J. Am. Chem. Soc. 2001, 123, 12917-12918
12917
Table 1. Asymmetric Hydrosilylations Using Catalytic CuH and
Roche BIPHEP Ligand 1
Ligand-Accelerated, Copper-Catalyzed Asymmetric
Hydrosilylations of Aryl Ketones
Bruce H. Lipshutz,* Kevin Noson, and Will Chrisman
Department of Chemistry & Biochemistry
UniVersity of California, Santa Barbara, California 93106
ReceiVed June 25, 2001
Within the field of catalytic asymmetric synthesis,1 hydrosi-
lylations of carbon-carbon and carbon-heteroatom double bonds
are viewed as a valued alternative to asymmetric hydrogenation.2
Since the first reports appeared about three decades ago, research
continues to focus on ketones and related systems (e.g., imines),3
with most of the methods relying on ligated rhodium hydride
catalysts.4 Impressive chemical yields and enantioselectivities of
product alcohols have also been documented from reactions
involving nonracemic titanium hydrides,5a-c and alternatives which
promote complexes of ruthenium can also effect such transforma-
tions.6 No single procedure appears to be ideal, each having its
virtues as well as limitations. Issues such as costs can be
associated with (1) the metal (e.g., Ru or Rh) or (2) the ligand
(e.g., nonracemic Brintzinger titanocenes),7 or both; (3) their
recovery and reuse, and potentially (4) the stoichiometric source
of hydride (e.g., PhSiH3). Finally, ratios in the 50-500:1 range2a
of substrate to either catalyst or ligand rarely approach those
associated with related hydrogenations.8 We now describe asym-
metric hydrosilylations of aryl ketones mediated by catalytic
quantities of bidentate phosphine-ligated copper hydride9 which
are efficient, occur under very mild conditions, afford competitive
levels of enantioselectivity, and can be performed with very high
ratios of substrate to ligand (S/L).
a Isolated. See ref 5d. b ee values were determined by conversion of
each product to its acetate and analysis by chiral capillary GC.
c Reaction was run at -78 °C. d Reaction was given 10 h at -50 °C
and then warmed to room temperature. e Reaction was run at -50 °C.
f R′ ) o-Br. g R′ ) m-Br. h R′ ) o-Cl.
Our recent observation10 that bidentate ligands (e.g., DPPF and
racemic BINAP) significantly enhance the rate of 1,2-reduction
of 4-tert-butylcyclohexanone by catalytic amounts of Stryker’s
reagent11a (hexameric (Ph3P)CuH) led to trials involving nonra-
cemic BINAP and various aryl ketones. Under a given set of
conditions (3 mol % (Ph3P)CuH, 3% BINAP, 0.34 equiv of
PMHS,12 toluene, -78 °C), acetophenone, propiophenone, and
R-tetralone gave good levels of enantioselectivity (75, 86, and
80% ee, respectively). A series of other ligands were screened,
including bidentate phosphines (e.g., BINAPFu,13a phanephos,13b
a hexafluoro-BINAP analog13c), P,N ligands (e.g., MAP),13d and
nonracemic diamines (e.g., PINDY),13e which in all cases led to
no observed reaction. Complete hydrosilylation was observed
employing JOSIPHOS,13f Trost’s ligand,13g DIOP,13h Et-ferro-
TANE,13i and Me-DuPHOS,13j although the enantioselectivity in
each case was low (<45% ee). On the basis of these results, we
returned to a bidentate diaryl-substituted phosphine as part of a
biaryl array (analogous to BINAP) which appeared to be critical
for selective stereoinduction.
(1) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds. ComprehensiVe
Asymmetric Catalysis I-III; Springer-Verlag: New York, 1999.
(2) (a) Nishiyama, H.; Itoh, K. Asymmetric Hydrosilylation and Related
Reactions. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley VCH:
New York, 2000; Chapter 2. (b) Waldman, T. E.; Schaefer, G.; Riley, D. P.
Discrete Chiral Rhodium Phosphine Complexes as Catalysts for Asymmetric
Hydrosilation of Ketones. In SelectiVity in Catalysis; Davis, M. E., Suib, S.
L., Eds.; American Chemical Society: Washington, DC, 1993.
(3) Verdaguer, X.; Lange, U. E. W.; Reding, M. T.; Buchwald, S. L. J.
Am. Chem. Soc. 1996, 118, 6784.
(4) (a) Sawamura, M.; Kuwano, R.; Ito, Y. Angew. Chem., Int. Ed. Engl.
1994, 33, 111. (b) Sudo, A.; Yoshida, H.; Saigo, K. Tetrahedron: Asymmetry
1997, 8, 3205. (c) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata,
M.; Kondo, M.; Itoh, K. Organometallics 1989, 8, 846.
(5) (a) Yun, J.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 5640. (b)
Rahimian, K.; Harrod, J. F. Inorg. Chim. Acta 1998, 270, 330. (c) Imma, H.;
Mori, M.; Nakai, T. Synlett 1996, 1229. (d) The products are known; cf.:
Carter, M. B.; Schiott, B.; Gutierrez, A.; Buchwald, S. L. J. Am. Chem. Soc.
1994, 116, 11667.
(6) (a) Zhu, G.; Terry, M.; Zhang, X. J. Organomet. Chem. 1997, 547, 97.
(b) Nishibayashi, Y.; Takei, I.; Uemura, S.; Hidai, M. Organometallics 1998,
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(7) Schafer, A.; Karl, E.; Zsolnai, L.; Huttner, G.; Brintzinger, H.-H. J.
Organomet. Chem. 1987, 328, 87; racemic ethylenebis(4,5,6,7-tetrahydro-1-
indenyl)titanium dichloride is listed at 500 mg for $375.00 from Strem
Chemicals (1999-2001 catalog).
(8) Ohkuma, T.; Kitamura, M.; Noyori, R. Asymmetric Hydrogenation. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley VCH: New York, 2000;
Chapter 1.
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(10) Lipshutz, B. H.; Chrisman, W.; Noson, K. J. Organomet. Chem. 2001,
624, 367.
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Soc. 1988, 110, 291. (b) Churchill, M. R.; Bezman, S. A.; Osborn, J. A.;
Wormald, J. Inorg. Chem. 1972, 11, 1818.
(12) PMHS ) poly(methylhydrosiloxane; a 29mer, with one hydride per
monomeric unit; MW 1900); CAS Registry No. 9004-73-3, available from
Lancaster Chemicals and used as received. Thus, 0.34 equiv of a 29mer is
(0.34 equiv × 29) or ca. 9-10 equiv of hydride per substrate.
(13) (a) Anderson, N. G.; Parvez, M.; Keay, B. A. Org. Lett. 2000, 2, 2817.
(b) Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider,
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Bella, M.; Langer, V.; Kocovsky, P. Org. Lett. 2000, 2, 3047. (f) Togni, A.;
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Am. Chem. Soc. 1992, 114, 9327. (h) Dumont, W.; Poulin, J. C.; Dang, T.-P.;
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10.1021/ja011529e CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/19/2001

12918 J. Am. Chem. Soc., Vol. 123, No. 51, 2001
Communications to the Editor
Table 2. Level of Roche Ligand 1 that Effects CuH-Catalyzed
Hydrosilylations
The extensive series of nonracemic biphenyl ligands originally
developed by Schmid, Scalone, and co-workers at Roche14a led
us to examine the parent species MeO-BIPHEP.14b The result
initially obtained with propiophenone (85% ee) paralleled that
with nonracemic BINAP. In switching to the dimethylphenyl
analogue, 3,5-xyl-MeO-BIPHEP (1), significant improvements in
enantioselectivity were observed, with ee values in most cases
exceeding 90%. Several illustrative examples of aryl ketones
reduced to their corresponding secondary alcohols 2 with 3 mol
% each of CuCl/NaO-t-Bu and this ligand (and thus, in the
absence of PPh3), along with PMHS as the hydride donor, is
shown in Table 1. Most hydrosilylations proceed at -50 °C in
12 h or less, while those at -78 °C can take up to ca. 2 days.
Chemical yields in all cases are high.5d Both electron-rich (entry
4) and electron-poor (entry 6) substrates react with comparable
selectivity, although in the latter case the reaction required less
time to reach completion. A few anomalous cases were noted,
including ortho-halo-substituted acetophenones (entry 8) and
1-acetylnaphthalene (not shown).15 Replacement of toluene by
THF as solvent afforded similar results.16 That the role of the
silane involves regeneration of CuH subsequent to the stereo-
defining 1,2-addition seems likely since no impact on rate or ee
was observed upon switching from PMHS to Ph2MeSiH.
t-Bu) in two additional cycles afforded from each the desired
product in the same chemical (>90%) and optical yields (92%
ee).
With substrate-to-catalyst ratios in these hydrosilylations at ca.
33:1, we questioned the need for a 1:1 stoichiometry between
CuH and ligand 1. It was not obvious that any significant
downward variation in the quantity of 1 would be tolerated, since
uncomplexed CuH is notoriously unstable.17 However, use at low
temperatures might extend its lifetime and allow for a decrease
in ligand stoichiometry. Toward this end, with acetophenone as
substrate, the amount of Cu(I) was held constant at 3 mol % as
the mol % of ligand 1 was lowered. As indicated in Table 2,
virtually identical results were obtained with levels of 1 as low
as 0.005 mol %, which corresponds to a substrate-to-ligand ratio
of 20,000:1. The amount of copper(I) could also be decreased
from 3.0 to 0.5 mol %, as could the number of equivalents of
PMHS from 0.34 to 0.14, while the net conversion was maintained
(>98.5% in 20 h). Identical treatment of propiophenone, which
led to results akin to those listed in Table 1 (i.e., 87-95%
chemical yields, 95-97% ee), suggests an element of generality,
which demonstrates S/L ratios normally reserved for asymmetric
hydrogenations.8
In summary, a reagent prepared in situ from catalytic quantities
of CuH and a nonracemic Roche ligand (R)- or (S)-3,5-xyl-MeO-
BIPHEP14 has been found to possess remarkable reactivity in
asymmetric hydrosilylations of aromatic ketones. Chemical yields
of isolated alcohol products are excellent, as are their optical
purities. These reductions take place in the presence of excess
PMHS as a source of hydride, and occur under especially mild
conditions within reasonable time frames. Given the combination
of a very inexpensive polymeric silane,12,18 along with <1 mol
% of a trivial copper(I) salt and exceedingly low levels of a
known, readily prepared nonracemic ligand,14 this technology
would appear to offer some unique and practical, as well as
economic, benefits relative to existing methods.2 Applications to
several other substrate types which may involve similar ligand-
accelerated catalysis are being pursued, results from which will
be reported in due course.
The stereochemical outcome, where either (R)-2 induces (R)-
alcohol 3 or (S)-2 induces the corresponding (S)-alcohol, can be
rationalized as shown in Figure 1. Steric interactions between
the conjugated aryl ring in the educt and a disubstituted aryl
moiety in the phosphine strongly disfavor transition state 4 relative
to 3.
Having invested up to 3 mol % of ligand 1 in the above
reactions, it seemed worthwhile to consider prospects for its
recovery and reuse. Upon completion of the hydrosilylation of
acetophenone, and after reaction workup, it was found that
following distillation of the product alcohol the residue could be
triturated with Et2O leading to isolation of ca. 75% of 1 initially
present. Reuse of recovered 1 (along with fresh CuCl and NaO-
Acknowledgment. We warmly acknowledge the NSF for financial
support. We are indebted to Drs. Rudolf Schmid and Michelangelo
Scalone (Hoffmann-La Roche, Basel) for a most generous supply of
BIPHEP ligands, as well as the senior authors in refs 13a-d for providing
some of the ligands used in this study.
Figure 1. Rationale for induction observed in CuH‚3,5-xyl-MeO-
BIPHEP-catalyzed hydrosilylations.
Supporting Information Available: Representative procedure and
data for asymmetric hydrosilylations associated with Table 1, along with
procedures for hydrosilylation with (PPh3)CuH/PMHS and BINAP‚CuH/
PMHS (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
(14) (a) Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.; Foricher,
J.; Lalonde, M.; Muller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure
Appl. Chem. 1996, 68, 131. Schmid, R.; Foricher, J.; Ceregetti, M.;
Schonholzer, P. HelV. Chim. Acta 1991, 74, 370. (b) Yun, J.; Buchwald, S.
L. Org. Lett. 2001, 3, 1129 and references therein.
(15) The corresponding alcohol was isolated in 99% yield, but with only
31% ee.
(16) With other toluene/THF mixtures (e.g., 80/20 toluene/THF, and 90/
10 toluene/THF) complete hydrosilylation of propiophenone was observed.
The yields and ee values of 2-phenylethanol were 95% and 97%, respectively,
for each of the above solvent combinations.
JA011529E
(17) Whitesides, G. M.; Stredronsky, E. R.; Casey, C. P.; San Filippo, J.
J. Am. Chem. Soc. 1970, 92, 1426.
(18) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin
Trans. 1 1999, 3381.