Synthesis and fluoride-promoted Wittig rearrangements of α-alkoxysilanes

Article abstract of DOI:10.1021/ol9909132

(matrix presented) Lewis acid-catalyzed reaction of allyl and benzyl trichloroacetimidates with α-silyl alcohols was found to be a general method for the synthesis of α-alkoxysilanes. Upon exposure to CsF, these α-alkoxysilanes could be made to undergo [2,3]-Wittig rearrangement with an efficiency similar to that realized by the analogous but inherently more toxic α-alkoxystannanes.

Full text of DOI:10.1021/ol9909132

ORGANIC
LETTERS
1999
Vol. 1, No. 7
1111-1113
Synthesis and Fluoride-Promoted Wittig
Rearrangements of r-Alkoxysilanes
Robert E. Maleczka, Jr.,* and Feng Geng
Department of Chemistry, Michigan State UniVersity, East Lansing, Michigan 48824
maleczka@cem.msu.edu
Received August 5, 1999
ABSTRACT
Lewis acid-catalyzed reaction of allyl and benzyl trichloroacetimidates with r-silyl alcohols was found to be a general method for the synthesis
of r-alkoxysilanes. Upon exposure to CsF, these r-alkoxysilanes could be made to undergo [2,3]-Wittig rearrangement with an efficiency
similar to that realized by the analogous but inherently more toxic r-alkoxystannanes.
For over 20 years Wittig rearrangements have elicited the
attention of synthetic and physical organic chemists alike.1
Reactions of this class are typically initiated by the formation
of an R-metalated ether which undergoes a subsequent
rearrangement, usually in the form of a [2,3]-, [1,2]-, or [1,4]-
shift. While direct deprotonation of an ether at the R-carbon,
usually facilitated by the presence of anion-stabilizing groups
such as carbonyls, nitriles, allyl, benzyl, or propargyl
moieties,1 can be used to initiate the sigmatropic event, this
approach is limited to those compounds possessing suf-
ficiently acidic R hydrogens. In 1978, Still and Mitra showed
that this restriction could be overcome by generating the
R-alkoxy carbanion via tin-lithium exchange.2 In the years
following their pioneering work, the Wittig-Still rearrange-
ment has earned its place as a powerful synthetic tool.
Despite its demonstrated potential, broad application of this
protocol has been governed by its reliance on the relatively
toxic3 organostannanes as well as the need for strong air-
and moisture-sensitive bases such as n-BuLi.
To circumvent these two limitations, we considered the
general possibility of R-alkoxysilanes being made to undergo
[2,3]-sigmatropic rearrangement by the action of fluoride
(Scheme 1). Not surprisingly such an approach has been the
Scheme 1
subject of prior, although very limited, investigations (Scheme
2).4-6 In fact prior to the original disclosure of Still,2 Reetz
(1) (a) Nakai, T.; Tomooka, K. Pure Appl. Chem. 1997, 69, 595-600.
(b) Nakai, T.; Mikami, K. Org. React. 1994, 46, 105-209. (c) Marshall, J.
A. In ComprehensiVe Organic Synthesis; Pattenden, G., Ed.; Pergamon:
London, 1991; Vol. 3, pp 975-1014. (d) Bru¨ckner, R. In ComprehensiVe
Organic Synthesis; Pattenden, G., Ed.; Pergamon: London, 1991; Vol. 6,
pp 873-908.
(3) (a) Chemistry of Tin; Smith, P. J., Ed.; Blackie Academic &
Professional: New York, 1998. (b) Davies, A. G. In Organotin Chemistry;
VCH: New York, 1997. (c) Pereyre, M.; Quintard, J.-P.; Rahm, A. In Tin
in Organic Synthesis; Butterworth: Toronto, 1987.
(2) Still, W. C.; Mitra A. J. Am. Chem. Soc. 1978, 100, 1927-1928.
(4) Reetz, M. T.; Greif, N. Chem. Ber. 1977, 110, 2958-2959.
10.1021/ol9909132 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/16/1999

Scheme 2
Scheme 3
tosylate R-hydroxybenzylsilane, nucleophilic displacement
of the product also failed to provide any of the desired ethers.
Several literature reports had demonstrated the compat-
ibility of R-hydroxysilanes to acid-catalyzed methylation and
acetalizations.11,13 Following this lead, we found that TM-
SOTf-catalyzed etherification of aliphatic, allylic, or benzylic
R-hydroxysilanes via the trichloroacetimidates of benzyl,
propargyl, and various allylic alcohols14 afforded the desired
R-alkoxysilanes typically in 50-70% yields15 after silica gel
chromatography (Scheme 3).
With our general route to R-alkoxysilanes in place, we
set out to explore the action of fluoride on these substrates.
Surveying several fluoride sources, we found that contrary
to previous reports, TBAF was not especially effective at
promoting Wittig rearrangement. For example, reaction of
2b with TBAF in the presence of 4 Å molecular sieves gave
the [2,3]-rearrangement product 4 in only 20% yield.
Similarly, neither tetrabutylammonium difluorotriphenyl-
stannate16 or KF provided any Wittig products. On the other
hand, CsF in DMF proved to be relatively efficient at the
promotion of [2,3]-Wittig rearrangements (Table 1). With
CsF all of our substrates capable of undergoing a [2,3]-shift
(2a-d) gave [2,3]-products in yields that were comparable
to the analogous lithium anion-initiated rearrangements.1
While the scope of this preliminary investigation limits
us in making any extensive stereochemical comparisons to
and Greif had shown4 (Scheme 2; entry 1) that the thermal
rearrangement of silylfluorene derivatives could be facilitated
by catalytic quantities of tetrabutylammonium fluoride
(TBAF). Several years later, Nakai reported5 the fluoride ion-
promoted [2,3]-Wittig rearrangement of two C-silylated
R-allyloxy esters (Scheme 2; entry 2). To our knowledge
the only other report of a fluoride triggered Wittig rear-
rangement was by Adam, who converted R-phenoxybenzyl-
silane into an alcohol which would appear to be the product
of a [1,2]-Wittig (Scheme 2; entry 3).6 However, the author
makes the point that this reaction proceeds via an intra-
molecular ipso-substitution as opposed to the radical pair
dissociation-recombination mechanism7 of an actual [1,2]-
Wittig rearrangement.
Given the mechanistic uncertainties and narrow substrate
scope of these previous studies, coupled with little advance-
ment of this field in over a decade, we decided to explore
the generality of fluoride-promoted Wittig rearrangements
of R-alkoxysilanes (Scheme 1). Key to our study would be
an examination of substrates which would allow the direct
comparison of R-alkoxysilanes with the more established
R-alkoxystannanes. Furthermore, we sought to determine if
such rearrangements could be carried out on relatively
unactivated substrates.
Upon beginning our study, we were quick to realize that
few general methods exist for the synthesis of R-alkoxy-
silanes with more complexity than that of the (TMS)methyl
ethers.8,9 (Perhaps one reason for the lack of progress in this
area.) Although the substituted R-hydroxysilanes (1) (Scheme
3) are easily obtained via retro-Brook rearrangement,10 the
alkylation of these alcohols in situ11 or under basic conditions
proved difficult.12 Furthermore, while we could efficiently
(10) (a) Linderman, R. J.; Ghannam, A. J. Am. Chem. Soc. 1990, 112,
2392-2398. (b) Brook, A. G.; Pascoe, J. D. J. Am. Chem. Soc. 1971, 93,
6224-6627. (c) Brook, A. G. Acc. Chem. Res. 1974, 7, 77-84. (d) Brook,
A. G.; Bassindale, A. R. In Rearrangements in Ground and Excited States;
de Mayo, P., Ed.; Academic Press: New York, 1980; Vol. 2, pp 149-227.
(11) For successful examples of an in situ methylation and silylation,
see: Murai, A.; Abiko, A.; Shimada, N.; Masamune, T. Tetrahedron Lett.
1984, 25, 4951-4954.
(12) For examples of some common side reactions under Williamson
ether conditions, see (a) Kreeger, R. L.; Menard, P. R.; Sans, E. A.; Shechter,
H. Tetrahedron Lett. 1985, 26, 1115-1118. (b) Sans, E. A.; Shechter, H.
Tetrahedron Lett. 1985, 26, 1119-1122. (c) Chakraborty, T. K.; Reddy,
G. V. J. Chem. Soc., Chem. Commun. 1989, 251-253.
(13) Tsuge, O.; Kanemasa, S.; Nagahama, H.; Tanaka, J. Chem. Lett.
1984, 1803-1806.
(14) Wessel, H. P.; Iversen, T.; Bundle, D. R. J. Chem. Soc., Perkin
Trans. 1 1985, 2247-2250.
(15) Varied regioselectivity was observed with trichloroacetimidates
derived from allylic alcohols. For example, etherification of 1a with the
trichloroacetimidate of crotyl alcohol gave a separable mixture of 2a (67%)-
and 2b (25%), while reaction of 1b with the trichloroacetimidate of cinnamyl
alcohol gave 2d, exclusively,
(5) Takahashi, O.; Maeda, T.; Mikami, K.; Nakai, T. Chem. Lett. 1986,
1355-1358.
(6) Adam, S. Tetrahedron 1989, 45, 1409-1414.
(7) (a) Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann. Chem. 1997,
1275-1281. (b) Maleczka, R. E., Jr.; Geng, F. J. Am. Chem. Soc. 1998,
120, 8551-8552 and references therein.
(8) (a) Suga, S.; Miyamoto, K.; Watanabe, M.; Yoshida, J. Appl.
Organomet. Chem. 1999, 13, 469-474. (b) Mulzer, J.; List, B. Tetrahedron
Lett. 1996, 37, 2403-2404 and references therein.
(9) For a retro [1,4]-Brook rearrangement approach to R-alkoxysilanes
see: Hoffmann, R.; Bru¨ckner, R. Chem. Ber. 1992, 125, 1471-1484.
(16) Gingras, M. Tetrahedron Lett. 1991, 32, 7381-7384.
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Org. Lett., Vol. 1, No. 7, 1999

events. Only entry 4 (Table 1) showed any propensity for
another Wittig manifold, providing the [1,2]-species as a
minor product. Only loss of the silyl group was observed
for other substrates (Table 1; entries 5-7) set up to undergo
[1,2]-Wittig rearrangement. This observation that the fluoride-
promoted rearrangements mimic their lithio counterparts
during the concerted [2,3]-shift, but not during the radical
pair dissociation-recombination driven [1,2]-Wittig rear-
rangement,20 suggests the involvement of a metal-associated
carbanionic intermediate. This would contrast with the
traditional Wittig-Still, for which Bru¨ckner21 has put forth
experimental evidence of a metal free carbanion. What is
less clear is whether these fluoride-promoted Wittigs involve
a pentavalent silicon intermediate8b,22 and/or the type of
cation coordinated species suggested by ab initio calcula-
tions.23
Table 1. Reaction of R-Alkoxysilanes with CsF17
Finally, it would appear that some activation of the starting
material (benzylic or allylic) is required. Aliphatic R-alkoxy-
silanes (Table 1; entry 8), for example, failed to react under
our conditions.
In summary, R-alkoxysilanes can be prepared via Lewis
acid-catalyzed reaction of allyl and benzyl trichloroacetimi-
dates with R-silyl alcohols and then made to undergo efficient
Wittig rearrangement by reaction with CsF in DMF. Further
synthetic and modeling studies aimed at expanding the scope
and increasing our mechanistic knowledge of these rear-
rangements are currently underway and will be reported in
due course.
Acknowledgment. Generous support was provided by the
NIH (HL-58114) and the MSU Department of Chemistry
(start-up funds for R.E.M. and a Harold Hart Graduate
Fellowship for F.G.). We also thank Dr. P. G. Spoors
(SmithKline Beecham) for valuable discussions.
the rearrangement of analogous R-lithio compounds, the
rearrangement of 2a did exhibit the same (albeit poor)
inherent stereochemical bias toward the erythro product, as
its lithio counterpart.1,18 Likewise, the exclusive E-olefin
formation observed in entries 2 and 4 (Table 1) would
suggest that the fluoride induced Wittigs proceed via the
same exo-transition state preferred by traditional Wittig
rearrangements.1,19
Supporting Information Available: Spectroscopic data
for all new compounds pictured as well as detailed experi-
mental procedures. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL9909132
Our initial results do indicate that efficient fluoride
promotion may be primarily limited to [2,3]-sigmatropic
(20) For data on the lithium base-promoted rearrangements of the
substrates in Table 1, see the accompanying letter (Maleczka, R. E., Jr.;
Geng, F. Org. Lett. 1999, 1, 1115-1118).
(17) All reactions were run with 3.0 equiv of CsF in DMF at room
temperature over 16 h. See Supporting Information for more details.
(18) Scho¨llkopf, U.; Fellenberger, K.; Rizk, M. Liebigs Ann. Chem. 1970,
734, 106-115.
(21) Kruse, B.; Bru¨ckner, R. Tetrahedron Lett. 1990, 31, 4425-4428.
(22) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. ReV. 1993,
93, 1371-1448.
(23) Wu, Y.-D.; Houk, K. N.; Marshall, J. A. J. Org. Chem. 1990, 55,
1421-1423.
(19) Rautenstrauch, V. J. Chem. Soc., Chem. Commun. 1970, 4-6.
Org. Lett., Vol. 1, No. 7, 1999
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