Hydrosilylation of aldehydes and ketones catalyzed by [Ph3P(CuH)]6

Article abstract of DOI:10.1016/S0022-328X(00)00903-7

Exposure of an aldehyde or ketone to ≤ 5 mol% (in copper) of Stryker's reagent [Ph₃P(CuH)]₆ in the presence of one of several silanes affords the corresponding protected alcohol in high yields. Aldehydes can be cleanly reduced in the presence of ketones.

Full text of DOI:10.1016/S0022-328X(00)00903-7

Journal of Organometallic Chemistry 624 (2001) 367–371
www.elsevier.nl/locate/jorganchem
Communication
Hydrosilylation of aldehydes and ketones catalyzed by
Ph P(CuH)]
[
3
6
Bruce H. Lipshutz *, Will Chrisman, Kevin Noson
Department of Chemistry and Biochemistry, Uni6ersity of California, Santa Barbara, CA 93106, USA
Received 6 October 2000; accepted 22 November 2000
Dedicated with warmest regards to Professor Jean Normant on the occasion of his 65th birthday
Abstract
Exposure of an aldehyde or ketone to 55 mol% (in copper) of Stryker’s reagent [Ph P(CuH)] in the presence of one of several
3
6
silanes affords the corresponding protected alcohol in high yields. Aldehydes can be cleanly reduced in the presence of ketones.
2001 Elsevier Science B.V. All rights reserved.
©
Keywords: Copper hydride; Hydrosilylation; Silyl ethers; Selective reductions
1. Introduction
Reduction of a non-conjugated aldehyde or ketone to
the corresponding alcohol is among the most funda-
mental transformations in organic chemistry. The pres-
ence of the resulting hydroxyl group in a molecule
oftentimes necessitates its masking during a synthetic
sequence, and thus enormous literature has also been
amassed over the years dedicated to providing alterna-
tives for protection of the alcohol function. This con-
version is most commonly viewed as a two-step/two-pot
sequence, notwithstanding extensive literature on hy-
drosilylation chemistry [1]. Although an impressive ar-
ray of protecting groups for the newly generated
alcohols has been developed [2], it would not be unrea-
sonable to suggest that silyl ethers play a leading role.
In this report we describe a new, especially mild and
efficient method which is catalytic in Cu(I) for the
direct one-pot conversion of aldehydes and ketones to
their (selected) silyl ether (or alcohol) derivatives (Eq.
(
1)
2
. Results and discussion
The procedure developed derives from our earlier
observation of the ease with which an enolate bearing a
presumed copper–oxygen bond undergoes transmetala-
tion with one of several arylsilanes [3]. Treatment of an
aldehydic substrate with catalytic amounts of Stryker’s
reagent (the hexamer of CuH·Ph P) [4] in toluene at
°C to room temperature in the presence of an aryl
silane (e.g. PhMe SiH) [5] leads to the silylated alcohol
essentially quantitatively. Since CuH·PPh3 alone ap-
pears to be sufficiently reactive to reduce an aldehyde
3
0
2
(
1)).
[
6], which is not true for the silane, the former species is
the likely reductant. The intermediate copper alkoxide
then undergoes transmetalation (perhaps via the four-
centered species 2) to arrive at product 1 with regenera-
tion of the catalyst (Scheme 1) [7]. Replacement of
*
Corresponding author. Tel.: +1-805-8932521; fax: +1-805-
8
938265.
E-mail address: lipshutz@chem.ucsb.edu (B.H. Lipshutz).
0
022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00903-7

3
68
B.H. Lipshutz et al. / Journal of Organometallic Chemistry 624 (2001) 367–371
Scheme 1. Regeneration of CuH·PPh3 via transmetalation.
Table 1
Hydrosilylations of aldehydes with cat CuH·PPh /PhMe SiH
a
3
2
CuH·PPh with a copper halide (e.g. CuCl/LiCl; 1:1)
led to no detectable reaction, not unexpected in light of
[9] give the corresponding silyl ethers (cf. Table 2 and
Eq. (2), respectively). Reactions with the latter reagents
require slight heating (ca. 40–45°C), although net effi-
3
Hosomi’s observations where the CuCl/PhMe SiH
2
3,4
combination requires heating in dimethylimidazolone
ciency of the process is not compromised . More
reactive PMHS [10], the least expensive silane of this
group, likewise gives an intermediate (polymeric) silyl
ether, which upon basic workup affords alcohols in
good yields. Table 3 highlights representative examples.
Levels of catalyst as low as 0.1 mol% are sufficient in
the case of aldehydes to arrive at similar results
(Scheme 2).
(
DMI) to generate ‘CuH’ [8]. Table 1 offers a sampling
of aldehydes that have been converted directly to their
silyl ethers. Under the conditions used, several func-
tional groups (e.g. esters, alkenes, alkynes, bromides,
1
nitro groups, etc.) are unaffected.
Other silanes, which lead to hydrolytically more ro-
bust derivatives [2], could also be employed as sources
2
of hydride. Thus, MePh SiH and even (t-Bu)Ph SiH
2
2
3
Excess silane could be recovered via Kugelrohr distillation (b.p.
1
Control experiments involving exposure of these functional
210–215°C at 1.5 mmHg) and reused.
4
groups to our standard conditions for hydrosilylation in the absence
of a substrate indicated no reduction had occurred in any case.
Triphenylsilane (Ph SiH) also reacts under similar conditions, as
3
expected, to afford a silylated alcohol in excellent yield (e.g. as in the
case of an aldehyde; Table 1, entry 7: yield=94%).
2
Available from Gelest Chemicals; catalog number SID44555.0.

B.H. Lipshutz et al. / Journal of Organometallic Chemistry 624 (2001) 367–371
369
yield of 94%. Interestingly, the presence of bidentate
phosphine ligands, such as DPPF and racemic BINAP,
in amounts equal to that of CuH·PPh , had a dramatic
3
effect on accelerating the rates of these hydrosilylations,
an observation which is now being pursued further.
(
2)
Differences in reactivity between aldehydes and ke-
tones could be exploited to selectively reduce the former
in the presence of the latter. As illustrated in Scheme 3,
a 1:1 mix of aldehyde 3 and ketone 4 led to products 5
and 6 in a 98.6:1.4 (GC) ratio; with alcohol 5 being
isolated in 94% yield after basic workup and column
chromatography. The same experiment conducted on
acyclic ketone 7 showed even greater chemoselectivity,
as 3 was fully reduced without a trace of alcohol 8
being noted by capillary GC analysis of the crude
reaction mixture. Moreover, ketone 7 was recovered to
the extent of 96%. While several other reagents exist for
the selective reduction of an aldehyde over a ketone
(
3)
In summary, a new method for hydrosilylation of
aldehydes and ketones has been uncovered which can
be used to arrive at silylated alcohols bearing any of
several commonly used silicon protecting groups. Con-
ditions are very mild, reagents are inexpensive, and the
amount of transition metal required can be as little as
0
.1 mol% in the case of aldehydes. Future efforts
directed at the asymmetric version of this copper(I)-me-
diated process as applied to unsymmetrically substi-
tuted ketones [12] are in progress and will be reported
in due course.
(
e.g. Raney Ni [11a], KBPh [11b], Bu SnH/Ti(0) [11c],
4 3
etc.), the catalytic CuH·PPh /silane combination is one
3
of the mildest and most economically attractive.
Manifested in the case of dihydrocarvone (9) is yet
another feature of this system (Eq. (3)). This substrate
was chosen to examine the integrity of an adjacent
stereogenic center upon ketone reduction. Catalytic
3
. Experimental
CuH·PPh3 in the presence of PhMe P and t-BuOH
2
3.1. Representati6e 1,2-reduction/silylation of an
aldehyde ((2-bromobenzyloxy)-diphenylmethylsilane;
Table 2, entry 1)
under an atmosphere of hydrogen has been reported to
epimerize these sites, presumably a consequence of
strongly basic conditions by virtue of the copper alkox-
ide generated in situ [6b]. While alkoxide intermediates
of this type may be at some point in our sequence
obligatory, their lifetime is minimized due to rapid
transmetalation with the silane present in solution.
Thus, conversion of 9 to its diphenylmethylsilyl ether
A dried 25 ml flask with a rubber septum top was
flushed with argon and charged with [PPh (CuH)] (53
3
6
mg, 0.162 mmol) as a red solid. Toluene (5.4 ml)
followed by neat diphenylmethylsilane (1.4 ml, 7.0
mmol) were added resulting in a homogeneous red
solution. In a second dry argon flushed vessel (10 ml)
with a rubber septum top 2-bromobenzaldehyde (0.63
10 occurred cleanly, favoring axial attack, to afford
only the expected two diastereomers in a combined
Table 2
a
Hydrosilylations using cat CuH·PPh /MePh SiH
3
2

3
70
B.H. Lipshutz et al. / Journal of Organometallic Chemistry 624 (2001) 367–371
Table 3
a
Hydrosilylations using cat CuH·PPh /PMHS /PMHSa followed by basic workup
3
Scheme 2. Hydrosilylations of aldehydes using only 0.1 mol% CuH·PPh3.
Scheme 3. Selective 1,2-reductions with CuH·PPh3.
ml, 5.4 mmol) and toluene (4 ml) were mixed, and the
oil. Kugelrohr distillation (168°C, 0.2–0.3 Torr) yielded
solution transferred via canula into the room tempera-
ture solution of copper and silane with stirring. The
reaction mixture was monitored by TLC (elution with
the title compound as a colorless oil (1.98 g, 95%).
1
H-NMR (400 MHz, CDCl ) l 0.70 (3H, s), 4.83 (2H,
3
s), 7.11 (1H, m), 7.32 (1H, dt, 7.6, 1.2, 0.8 Hz), 7.40
(6H, m), 7.48 (1H, dd, 8.0, 1.2 Hz), 7.63 (5H, m).
5
% diethyl ether/hexane, R =0.74); the aldehyde was
f
13
consumed after 30 min. The reaction was filtered
C-NMR (100 MHz, CDCl
3
) l −2.94, 65.02, 121.46,
through a pad of Celite/charcoal, washed with EtOAc
127.53, 128.08, 128.14, 128.54, 130.18, 132.28, 134.52,
−
1
(
2×15 ml), and the filtrate concentrated in vacuo to an
135.76, 139.80. IR (neat) cm
3069, 3047, 3022, 2953,

B.H. Lipshutz et al. / Journal of Organometallic Chemistry 624 (2001) 367–371
371
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1
957, 1888, 1820, 1770, 1590, 1569, 1429, 1255, 1203;
LREIMS (m/z, rel. int.) 369(100), 339(9), 306(18),
[
[
289(8), 257(5), 245(7), 225(13), 211(17), 197(33),
183(37), 169(44), 149(33), 139(12), 121(8), 105(24),
90(33), 77(13), 57(10); HREIMS Calc. for C H BrOSi
3
20
19
+
67.0154, Found 367.0152 [M −CH ].
3
(
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Acknowledgements
[
2
Financial support provided by the NSF (CHE 97-
4813) and NIH (GM 56764) is warmly acknowledged
with thanks.
Stryker, Tetrahedron 56 (2000) 2153.
[
[
[
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3
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