P(MeNCH2CH2)3N: An Efficient Promoter for the Reduction of Aldehydes and Ketones with Poly(methylhydrosiloxane)

Full text of DOI:10.1021/jo990624r

J . Org. Chem. 1999, 64, 8021-8023
8021
Ta ble 1. Red u ction of Ald eh yd es w ith P MHS Usin g 1 a s
a P r om oter a
P (MeNCH2CH2)3N: An Efficien t P r om oter
for th e Red u ction of Ald eh yd es a n d
Keton es w ith P oly(m eth ylh yd r osiloxa n e)
Zhigang Wang, Andrzej E. Wroblewski,‡ and
J ohn G. Verkade*
Department of Chemistry, Iowa State University,
Ames, Iowa 50011-3111
Received April 13, 1999
The reduction of carbonyl compounds by hydrosilyla-
tion is one of the most effective methods for the synthesis
of alcohols.1 The reactivity of organosilicon reagents, such
as trialkoxysilanes and trihalogenated silanes, in these
reactions is enhanced by coordination with Lewis bases
such as fluoride2 or DMF.3 Upon reaction with diols or
amino alcohols, these reagents can form pentacoordinate
hydrosilicate intermediates4 that efficiently reduce alde-
hydes and ketones to the corresponding alcohols.5 Asym-
metric reductions have also been achieved using chiral
diols or chiral amino alcohols to give optically active
alcohols with good to excellent ee’s.6
Recently, polymethylhydrosiloxane (PMHS), an inex-
pensive and stable siloxane polymer has been extensively
used in the reduction of imines,7 azides,8 and esters9 in
the presence of a catalyst. Although aldehydes and
ketones can be reduced by PMHS in the presence of
fluoride,2 bis(dibutylacetoxytin),10 or ZnCl2,11 the yields
are modest or else rather harsh reaction conditions must
be employed. During our ongoing investigation of new
synthetic applications of 1,12 a commercially available
nonionic base (Strem) originally synthesized in our
laboratories,13 we found that 1 promotes the allylation
a
All reactions were conducted at room temperature for 1 h
under argon. The THF was freshly distilled over Na and stored
over 4 Å molecular sieves. Isolated yield based on the aldehyde.
b
of aromatic aldehydes with allyltrimethylsilane.14 This
prompted us to determine whether 1 can activate Si-H
bonds in PMHS to reduce carbonyl compounds. Herein
we report that aldehydes and ketones are reduced under
mild conditions by PMHS in the presence of catalyst 1,
giving the corresponding alcohols in high yield.
As seen in Table 1, a variety of aromatic aldehydes
were smoothly reduced to the corresponding alcohols in
high yields with survival of the aromatic chloro, nitro,
cyano, and methoxy substituents. Conjugated as well as
isolated double bonds also remained intact during regi-
oselective reduction of the carbonyl groups. Aliphatic
aldehydes are reduced to the corresponding alcohols in
high yields even though such aldehydes undergo aldol
condensation in the presence of catalyst 1.15 We assume
that under the present reaction conditions equilibrium
1 is rapidly established and lies sufficiently far to the
right that aldol condensation via initial deprotonation of
the aldehyde by 1 is effectively suppressed.
‡ On leave of absence from the Institute of Chemistry of the Medical
University of Lo`dz´, Poland.
(1) (a) Ojima, J . Synth. Org. Chem. J pn. 1974, 32, 687. (b) Nagai,
Y. Org. Prep. Proc. Int. 1980, 12, 13. (c) Matsumoto, H.; Hoshino, Y.;
Nagai, Y. Bull. Chem. Soc. J pn. 1981, 54, 1279.
(2) (a) Chrit, C.; Corriu, R. J . P.; Perz, R.; Reye, C. Synthesis 1982,
981. (b) Drew, M. D.; Lawrence, N. J .; Fontaine, D.; Sehkri, L. Synlett
1997, 989.
(3) Kobayashi, S.; Yasuda, M.; Hachiya, I. Chem. Lett. 1996, 407.
(4) Chuit, C.; Corriu, R. J . P.; Reye, C.; Young, J . C. Chem. Rev.
1993, 93, 1371 and references therein.
(5) (a) Hosomi, A.; Hayashida, H.; Kohra, S.; Tominaga, Y. J . Chem.
Soc., Chem. Commun. 1986, 1411. (b) Kira, M.; Sato, K.; Sakurai, H.
Chem. Lett. 1987, 2243. (c) Kira, M.; Sato, K.; Sakurai, H. J . Org.
Chem. 1987, 52, 948.
(6) (a) Kohra, S.; Hayashida, H.; Tominaga, Y.; Hosomi, A. Tetra-
hedron Lett. 1988, 29, 89. (b) Schiffers, R.; Kagan, H. B. Synlett 1997,
1175.
(7) (a) Verdaguer, X.; Lange, U. E. W.; Buchwald, S. L. Angew.
Chem., Int. Ed. 1998, 37, 1103. (b) Lopez, R. M.; Fu, G. C. Tetrahedron
1997, 53, 16349.
(8) Hays, D. S.; Fu, G. C. J . Org. Chem. 1998, 63, 2796.
(9) (a) Barr, K. J .; Berk, S. C.; Buchwald, S. L. J . Org. Chem. 1994,
59, 4323. (b) Breeden, S. W.; Lawrence, N. J . Synlett 1994, 833.
(10) Lipowitz, J .; Bowman, S. A. J . Org. Chem. 1973, 38, 162.
(11) Chandrasekhar, S.; Reddy, Y. R.; Ramarao, C. Synth. Commun.
1997, 27, 2251.
(12) (a) Tang, J . S.; Verkade, J . G. Angew. Chem., Int. Ed. Engl.
1993, 32, 2, 896. (b) Tang, J . S.; Mohan, T.; Verkade, J . G. J . Org.
Chem. 1994, 59, 4931. (c) D’Sa, B.; Verkade, J . G. J . Org. Chem. 1996,
61, 2963. (d) D’Sa, B.; Verkade, J . G. J . Am. Chem. Soc. 1996, 118,
12832. (e) D’Sa, B.; McLeod, D.; Verkade, J . G. J . Org. Chem. 1997,
62, 5057. (f) D’Sa, B.; Kisanga, P.; Verkade, J . G. J . Org. Chem. 1998,
63, 3961. (g) Kisanga, P.; D’Sa, B.; Verkade, J . G. J . Org. Chem., in
press. (h) Kisanga, P.; Verkade, J . G. J . Org. Chem., accepted.
(13) Verkade, J . G. Coord. Chem. Rev. 1994, 137, 233.
Table 2 shows that aromatic ketones are also efficiently
reduced. Although the ester group in the fourth substrate
in this table remained intact in the product, the product
yield is only modest. This may be due to a partial
reduction of the ester functionality. When 4-acetoxyace-
tophenone (2) was subjected to reduction with PMHS
(14) Wang, Z.; Kisanga, P.; Verkade, J . G. Research in progress.
(15) D’Sa, B. A.; Kisanga, P.; Verkade, J . G. J . Org. Chem., 1998,
63, 3961.
10.1021/jo990624r CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/29/1999

8022 J . Org. Chem., Vol. 64, No. 21, 1999
Notes
Ta ble 2. Red u ction of Keton es w ith P MHS Usin g 1 a s a
P r om oter a
Sch em e 1
The mechanistic rationale proposed in Scheme 1 paral-
lels that put forth earlier for the reduction of carbonyl
compounds with hypervalent hydrosilicates.2-6 The phos-
phorus atom in 1 initially coordinates with a silicon atom
in PMHS to form the corresponding pentacoordinate
hydrosilicate 1y‚PMHS. The pentacoordinate silicate then
further coordinates a carbonyl group to form a hexaco-
ordinate hydrosilicate followed by H transfer to the
carbonyl carbon to form the silyl ether linkage. The
alcohol is formed during workup in aqueous NaOH or in
HF/CH3CN. The role of 1 as a Lewis base stems from its
ability to form a transannular bond between the bridge-
head N and P atoms. This bond, which renders the
phosphorus electron rich, facilitates phosphorus coordi-
nation to the silicon atom to form the pentacoordinate
silicate. When P(NMe2)3, which lacks this electron en-
richment mechanism, was employed under the present
conditions, no detectable reduction product was observed.
The 29Si NMR spectrum of PMHS in the presence of 1
equivalent of 1 also provides evidence for the pathway
shown in Scheme 1. Thus the 29Si chemical shifts for
PMHS in C6D6 (-31.06, -37.34 ppm) disappear and are
replaced by two new peaks (-62.23 and -67.20 ppm).
These upfield shifts are consistent with an increase in
silicon coordination number from four to five16 and an
equilibrium 1 that favors 1y‚PMHS.
a
All reactions were conducted at room temperature for 12 h
under argon. THF was freshly distilled over Na and stored over 4
Å molecular sieves. Isolated yield based on the ketone. c Deter-
b
mined by GC based on ketone.
followed by acidic workup, up to 25% of 4-hydroxyace-
tophenone was found in the crude reaction mixture. In a
separate experiment it was shown that no hydrolysis of
the acetate group of 2 occurred under the acidic condi-
tions employed. When 4-benzoyloxyacetophenone was
similarly reduced with PHMS, proton signals of benzyl
alcohol as well as of 4-hydroxyacetophenone were de-
tected in the crude reaction product. Incomplete reduc-
tions of the carbonyl group were observed in these
experiments. No reduction of the carbonyl group in ethyl
acetoacetate or of 4-nitro-2-butanone was detected, while
only partial reductions were found for 2-(phenylsulfonyl)-
acetophenone (20%) and diethyl (2-oxo-2-phenylethyl)-
phosphonate (15%). Like the unsaturated aldehydes in
Table 1, the unsaturated ketone 4-phenylbut-3-en-2-one
(Table 2) underwent chemoselective reduction of the
carbonyl group in the presence of the olefinic bond.
However 2-decanone, cyclohexanone, and 4-tert-butylcy-
clohexanone gave only moderate yields of product (trans
in the case of the last reactant), and the sterically
hindered ketone, 2,6-dimethylcyclohexanone, gave the
corresponding alcohol in low yield.
Although 1 acts catalytically in these reductions, it is
actually a promoter inasmuch as 1 is hydrolyzed during
the aqueous workup that liberates the alcohol from the
silyl ether.
Exp er im en ta l Section
In a typical procedure for the reactions in Tables 1 and 2, a
solution of 1 (0.1 mmol) in THF (1.0 mL) at 0 °C was slowly
added to 1.0 mL of a solution of PMHS (0.1 mL, 1.7 mmol) and
the aldehyde or ketone (1.0 mmol) in THF (1.0 mL). After the
reaction solution was stirred at room temperature (1 h for the
aldehydes and 12 h for the ketones) an aqueous solution of
NaOH (10%, 5 mL) and ether (10 mL) was added, and the
mixture was then stirred at room temperature for another 1 h.
Alternatively, for base-sensitive compounds, the crude reaction
That aldehydes are reduced much more rapidly under
our conditions than ketones was shown by the reduction
of an equimolar mixture of benzaldehyde and acetophe-
none which gave a corresponding product ratio of 92:8,
respectively. Thus chemoselective reduction of an alde-
hyde group in the presence of a keto functionality can
be accomplished.
(16) Kobayashi, S.; Nishio, K. J . Org. Chem. 1994, 59, 6620 and
references therein.

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8023
mixture was added to a cooled (0 °C) solution of 48% HF (0.5
mL) in acetonitrile (5 mL). The mixture was stirred at room
temperature for 1 h followed by addition of ether (30 mL). The
phases were separated, and the water layer was washed with
ether (3 × 10 mL). The organic layers were combined, washed
with brine (3 × 10 mL), and then dried over MgSO4. The solvent
was removed with a rotary evaporator and then under vacuum
to give the crude product which was purified by flash chroma-
tography (hexane:ethyl acetate ) 10:1) to give the alcohol.
American Chemical Society, for support of this research
through a grant.
Su p p or tin g In for m a tion Ava ila ble: References contain-
ing 1H and 13C NMR spectral data with which our product
spectra compared favorably. This material is available free of
charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. The authors thank the donors
of the Petroleum Research Fund, administered by the
J O990624R