Direct conversion of β-hydroxyketones to cyclic disiloxanes

Article abstract of DOI:10.1021/ol1024635

β-Hydroxyketones can be directly converted to cyclic disiloxanes using diphenylchlorosilane in the presence of imidazole and an amine base. The reaction is proposed to proceed via a nucleophilic activation mechanism through a cyclic chairlike transition state affording hydrosilylated products with high diastereoselectivity.

Full text of DOI:10.1021/ol1024635

ORGANIC
LETTERS
2010
Vol. 12, No. 22
5350-5353
Direct Conversion of ꢀ-Hydroxyketones
to Cyclic Disiloxanes
Gregory W. O’Neil,* Michael M. Miller, and Kyle P. Carter
Department of Chemistry, Western Washington UniVersity, Bellingham,
Washington 98225, United States
oneil@chem.wwu.edu
Received October 11, 2010
ABSTRACT
ꢀ-Hydroxyketones can be directly converted to cyclic disiloxanes using diphenylchlorosilane in the presence of imidazole and an amine base.
The reaction is proposed to proceed via a nucleophilic activation mechanism through a cyclic chairlike transition state affording hydrosilylated
products with high diastereoselectivity.
Carbonyl hydrosilylation represents a mild and selective
alternative to main-group metal hydrides for the introduction
Scheme 1. Preparation of Hydridosilyl Ethers
of hydroxyl functionality.1 Ongoing research has produced
examples of both Lewis acid-2 and Lewis base-mediated3
hydrosilylations along with various transition metal catalysts4
for this purpose. As part of an ongoing program investigating
the intramolecular hydrosilylation of prochiral ꢀ-silyloxyke-
tones, we set out to prepare several hydridosilyl ethers of
type 1 with differing silicon substitution as it is known that
substituents on silicon can have a profound influence on
stability and reactivity (Scheme 1).5 While the diisopropyl-
and di-tert-butyl derivatives were generated without incident
by silylation of 26 with the appropriate dialkylchlorosilane
(1.2 equiv) in the presence of imidazole (2.5 equiv),
formation of the corresponding diphenylhydridosilyl ether
3 was accompanied by small amounts of cyclic disiloxane
4.7
(1) For a recent review, see: Larson, G. L.; Fry, J. L. Ionic and
Organometallic-Catalyzed Organosilane Reductions. Organic Reactions;
Denmark, S. E., Ed.; John Wiley & Sons Inc.: New York, 2008; Vol. 71.
(2) For select examples, see: (a) Fry, J. L.; Orfanopoulos, M.; Adlington,
M. G.; Dittman, W. R., Jr.; Silverman, S. B. J. Org. Chem. 1978, 43, 374.
(b) Doyle, M. P.; West, C. T.; Donnelly, S. J.; McOsker, C. C. J. Organomet.
Chem. 1976, 117, 129. (c) Piers, W. E.; Chivers, T. Chem. Soc. ReV. 1997,
345.
(3) For select examples, see: (a) Boyer, J.; Corriu, R. J. P.; Perz, R.;
Reye, C. J. Organomet. Chem. 1978, 148, C1. (b) Boyer, J.; Corriu, R. J. P.;
Perz, R.; Reye, C. J. Chem. Soc., Chem. Commun. 1981, 121. (c) Fry, J. L.;
McAdam, M. A. Tetrahedron Lett. 1984, 25, 5859. (d) Kira, M.; Sato, K.;
Sakurai, H. J. Org. Chem. 1987, 52, 948.
(5) Morkin, T. L.; Leigh, W. J. Acc. Chem. Res. 2001, 34, 129. (b) Parisa,
S. I. M.; Lemke, F. R. Inorg. Chem. Commun. 2005, 8, 425. (c) Denmark,
S. E.; Neuville, L.; Christy, M. E.; Tymonko, S. A. J. Org. Chem. 2006,
´
71, 8500. (d) Duczmal, W.; Maciejewska, B.; Sliwinska, E.; Mareiniec, B.
(4) For select examples see: (a) [Re] catalyst: Kennedy-Smith, J. J.;
Nolin, K. A.; Gunterman, H. P.; Toste, F. D. J. Am. Chem. Soc. 2003, 125,
4056. (b) [Cu] catalyst: Kaur, H.; Kauer Zinn, F.; Stevens, E. D.; Nolan,
S. P. Organometallics 2004, 23, 1157. Lipshutz J. Organomet. Chem. 2001,
624, 367. (c) [Au] catalyst: J. Organomet. Chem. 2007, 692, 1799. (d) [Ni]
catalyst: Tran, B. L.; Pink, M.; Mindiola, D. J. Organometallics 2009, 28,
2234.
Trans. Met. Chem. 1995, 20, 162.
(6) Khan, A. T.; Parvin, T.; Choudhury, L. H.; Ghosh, S. Tetrahedron
Lett. 2007, 48, 2271.
(7) (a) For a previous example of ketone reductions with diphenylsilane,
see: Gilman, H.; Diehl, J. J. Org. Chem. 1961, 26, 4817-4820. (b) For a
recent tandem silylation/hydrosilation, see: Shchepin, R.; Xu, C.; Dussault,
P. Org. Lett. 2010, ASAP, DOI: 10.1021/ol1018757.
10.1021/ol1024635  2010 American Chemical Society
Published on Web 10/27/2010

In general, organosilicon hydrides do not undergo spon-
taneous reactions with organic compounds unless the organic
substrate is a reasonably strong electrophile or the silane has
been first activated by the interaction of a nucleophilic species
with the silicon center. It was thought that, in analogy to
other Brønsted acid catalyzed carbonyl hydrosilylation reac-
tions,8 HCl (presumably as the imidazolium salt) liberated
during the course of the reaction might serve to activate the
carbonyl oxygen facilitating delivery of hydride from silicon.
Attempts to increase the amount of hydrosilylation product
by treatment of a mixture of 3 and 4 with various acids
including imidazolium hydrochloride, however, met with
failure, the reactions affording predominantly desilylated
starting material and/or decomposition under more forcing
conditions (Scheme 2).
ration, and the product was flushed through a plug of Florisil
to remove unreacted starting material.
To test the generality of the reaction, several ꢀ-hydrox-
yketones were prepared11 and subjected to our optimized
hydrosilylation conditions (Scheme 4). The sensitive cyclic
Scheme 4. Hydrosilylation/Desilylation 1,3-Diol Synthesis
Scheme 2.
Attempted Acid-Mediated Hydrosilylationa
siloxane products thus obtained were directly converted the
corresponding 1,3-diols by treatment with TBAF. As can
be seen from the results, both aryl- and alkyl-ꢀ-hydroxyke-
tones were reduced in comparable yield. Alkene functionality
in the cinnamaldehyde-derived substrate was not hydrosi-
lylated under these reaction conditions.12 The reaction did
however prove somewhat sensitive to steric and electronic
deactivation, both the tert-butyl and methoxybenzene sub-
strates giving lower conversion under identical reaction
conditions.
a H+ ) PPTS, CSA, (PhO)2P(O)OH, imidazole·HCl.
Alternatively, in an attempt to make the reaction more
basic, various amine additives were evaluated for their ability
to promote the formation of 4 (Scheme 3). It was found that
While the overall mechanism for this transformation is
still under investigation, several statements can be made
concerning the role of certain reagents and intermediates
based on the following observations: Imidazole is essential
for hydrosilylation to occur. Reactions performed without
imidazole and only triethylamine did not afford cyclic
siloxane products, giving predominantly noncyclized ꢀ-hy-
dridosilyloxyketones of type 3 (Scheme 5, eq 1). However,
using a large excess of imidazole did not increase the amount
of hydrosilylated product obtained. Moreover, substituting
imidazole for DMAP or N-methylimidazole (NMI) failed to
produce any of the hydrosilylation product as detectable by
1H NMR. ꢀ-Hydroxy functionality is necessary for carbonyl
hydrosilylation under these reaction conditions. Treatment
of propiophenone with diphenylchlorosilane, imidazole, and
Scheme 3. Base-Promoted Cyclic Siloxane Formation
upon addition of triethylamine or Hu¨nig’s base to the reaction
mixture containing imidazole, the amount of hydrosilylated
product was substantially increased, 2 and 5 directly con-
verted to disiloxanes 4 and 6, respectively.9 The products 4
and 6 proved highly susceptible to hydrolysis of one or more
Si-X bonds giving a complex mixture of products upon
aqueous workup or attempted purification on silica.10 Pure
material could be obtained for analysis, albeit in low yield,
by performing the reaction with an excess of ꢀ-hydroxyke-
tone substrate relative to diphenylchlorosilane. Ammonium
salts generated during the reaction were removed by tritu-
(11) ꢀ-Hydroxyketone substrates were prepared according to the fol-
lowing general protocol described in :Martin, V. A.; Murray, D. H.; Pratt,
N. E.; Zhao, Y. B.; Albizati, K. F. J. Am. Chem. Soc. 1990, 112, 6965.
(8) (a) Anwar, S.; Davis, A. P. J. Chem. Soc., Chem. Commun. 1986,
831. (b) Davis, A. P.; Anwar, S. Tetrahedon 1988, 44, 3761.
(9) For a recent example of reductions involving a phenylsilane and
triethylamine, see: Frost, C. G.; Hartley, B. C. J. Org. Chem. 2009, 74,
3599.
(10) For another report on diphenylsiloxane instability, see: Blackwell,
J. E.; Foster, K. L.; Beck, V. H.; Piers, W. E. J. Org. Chem. 1999, 64,
4887.
(12) For a review of alkene hydrosilylation, see:Yamamoto, K.; Hayashi,
T. Hydrosilylation of olefins. In Transition Metals for Organic Synthesis;
Beller, M., Bolm, C., Eds.; 1998; Vol. 2, p 120.
Org. Lett., Vol. 12, No. 22, 2010
5351

ity of the diphenylchlorosilane compared to di-tert-butyl and
diisopropyl derivatives. While the failure of N-methylimi-
dazole to promote hydrosilylation could suggest a nucleo-
philic/electrophilic role for imidazole16 with activation of
the carbonyl through N-H hydrogen bonding,17 the role of
triethylamine might also be explained by promoting silicate
formation through abstraction of this proton.18 Attempts to
further elucidate the mechanism by in situ 1H and 29Si NMR
analysis failed to produce evidence of an intermediate
pentacoordinate silicate;19 however, stepwise hydridosily-
loxyketone and subsequent cyclic disiloxane formation were
clearly observed.
Scheme 5. Hydrosilylation Specificity
triethylamine gave exclusively starting material even after
prolonged reaction times as detectable by 1H NMR (Scheme
5, eq 2).
If the hydride is indeed delivered intramolecularly pro-
ceeding through a rigid chairlike transition state, it was
anticipated that the reaction might occur with high levels of
diastereoselectivity. To test this, ketoalcohols 7-920 were
prepared and subjected to hydrosilylation conditions followed
by desilylation with TBAF (Scheme 7). In all cases, the
On the basis of these observations, the reaction is proposed
to proceed through a nucleophilic activation mechanism.13
It has been shown that otherwise unreactive organosilicon
hydrides will react with carbonyl compounds when certain
nucleophilic species are added.13 This is thought to arise from
the formation of an intermediate valence-expanded, penta-
coordinate hydrosilanide that is a stronger reducing agent
than the tetravalent precursor.14 Imidazole in this regard
occupies a central role, with several imidazolium silicates
having been characterized by NMR and X-ray diffraction.15
It is therefore assumed that the observed cyclic disiloxane
product is the result of imidazole activation post hydridosi-
lylether formation (Scheme 6).
Scheme 7
.
Diastereoselective Intramolecular Hydrosilylationa
Scheme 6
.
Proposed Mechanism for Direct Disiloxane
Formation
a
1
Determined by H NMR.
corresponding 1,3-diol products (10-12) were obtained in
good yield and with high diastereoselectivity. A comparison
of spectral data to that reported in the literature20,21 and/or
The developing negative charge at silicon can be stabilized
by the phenyl substituents explaining the differential reactiv-
(16) (a) Chopra, S. K.; Martin, J. C. J. Am. Chem. Soc. 1990, 112, 5342.
(b) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org. Chem. 2000, 65,
3090.
(13) For select examples of Lewis basic activation of silanes as reducing
agents, see: (a) Gan, L.; Brook, M. Can. J. Chem. 2006, 84, 1416. (b)
Riduan, S. N.; Zhang, Y. G.; Ying, J. Y. Angew. Chem., Int. Ed. 2009, 48,
3322. (c) Malkov, A. V.; Liddon, A. J. S.; Ram´ırez-Lo´pez, P.; Bendova´,
L.; Haigh, D.; Kocˇovsky´, P. Angew. Chem., Int. Ed. 2006, 45, 1432. (d)
Tan, M.; Zhang, Y.; Ying, J. Y. AdV. Synth. Catal. 2009, 351, 1390.
(14) Gronert, S.; Glaser, R.; Streitwieser, A. J. Am. Chem. Soc. 1989,
111, 3111.
(17) Taylor, R.; Kennard, O.; Versichel, W. J. Am. Chem. Soc. 1983,
105, 5761.
(18) For an example of coordinated imidazole stabilization by amines,
see: Balch, A. L.; Watkins, J. J.; Doonan, D. J. Inorg. Chem. 1979, 18,
1228.
(19) Wang, Z.; Wroblewski, A. E.; Verkade, J. G. J. Org. Chem. 1999,
64, 8021.
(15) (a) Boyer, J.; Corriu, R. J. P.; Kopton, A.; Mazhar, M.; Poirier,
M.; Royo, G. J. Organomet. Chem. 1986, 301, 131. (b) Brelie`re, C.; Carre`,
F.; Corriu, R. J. P.; Poirier, M.; Royo, G. Organometallics 1986, 5, 388.
(c) Boyer, J.; Brelie`re, C.; Corriu, R. J. P.; Kopton, A.; Poirier, M.; Royo,
G. J. Organomet. Chem. 1986, 311, C39–C43.
(20) Yakura, T.; Yoshimoto, Y.; Ishida, C.; Mabuchi, S. Tetrahedron
2007, 63, 4429–4438.
(21) For a previous synthesis of 10, see: Marimganti, S.; Wieneke, R.;
Geyer, A.; Maier, M. E. Eur. J. Org. Chem. 2007, 17, 2779
.
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Org. Lett., Vol. 12, No. 22, 2010

detailed NMR analysis after conversion to the cyclic acetal22
revealed that each of the reactions occurred with the same
sense of diastereoselection. The formation of syn-propionate
products can be rationalized as a preference for the methyl
group to assume an equatorial position at the transition state.
In summary, ꢀ-hydroxyketones can be directly converted
to cyclic disiloxanes under mild conditions using diphenyl-
chlorosilane promoted by imidazole in the presence of
triethylamine. The reaction is thought to proceed by coopera-
tive Lewis base activation of silicon affording a transient
hydridosilicate, that then delivers hydride to the carbonyl
carbon intramolecularly via a chairlike transition state. This
proposed mechanism is consistent with the diastereoselec-
tivity observed for the reduction of compounds 7-9. Current
efforts are aimed at elucidating the complete mechanism for
this transformation, further examining the substrate scope,
and highlighting the utility of this protocol in the context of
complex natural product synthesis.
Acknowledgment. Financial support from Western Wash-
ington University, M.J Murdoch Charitable Trust, and an
award from Research Corporation is gratefully acknowl-
edged.
(22) See Supporting Informationfor details.
Supporting Information Available: Experimental pro-
cedures and spectral data for compounds 4, 6, 7, 8, 10, 11,
and 12. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL1024635
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