Studies on the deprotonation and subsequent [1,4]-Wittig rearrangement of α-benzyloxyallylsilanes

Article abstract of DOI:10.1016/j.tetlet.2006.07.018

Upon exposure to s-BuLi, benzyloxyallylsilane undergoes an unusually rapid and efficient [1,4]-Wittig rearrangement. Herein we describe efforts aimed at trapping the intermediate α-carbanion with an electrophile prior to rearrangement. The results of thes

Full text of DOI:10.1016/j.tetlet.2006.07.018

Tetrahedron Letters 47 (2006) 6565–6568
Studies on the deprotonation and subsequent
[1,4]-Wittig rearrangement of a-benzyloxyallylsilanes
Edith N. Onyeozili and Robert E. Maleczka, Jr.*
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
Received 22 June 2006; revised 6 July 2006; accepted 6 July 2006
Available online 31 July 2006
Abstract—Upon exposure to s-BuLi, benzyloxyallylsilane undergoes an unusually rapid and efficient [1,4]-Wittig rearrangement.
Herein we describe efforts aimed at trapping the intermediate a-carbanion with an electrophile prior to rearrangement. The results
of these experiments indicate that a-deprotonation and bond reorganization are separate events. Findings herein further indicate
that the future success of benzyloxyallylsilanes in [1,4]-Wittig rearrangements will likely hinge on the acidity of the benzylic protons.
Ó 2006 Elsevier Ltd. All rights reserved.
In an earlier letter,1 we described the [1,4]-Wittig rear-
rangement2 of benzyloxyallylsilane (1) (Scheme 1).
Upon treatment with s-BuLi, compound 1 rapidly
undergoes the [1,4]-Wittig shift to afford enolate 2 in
high yield after only 30 min at ꢀ75 °C. To the best of
our knowledge, this represents the most rapid, selective,
and efficient [1,4]-Wittig rearrangement of a-alkoxysil-
anes in particular, and allyl benzyl ethers in general, ever
reported. Furthermore, enolate 2 could be effectively
quenched with various electrophiles to generate a range
of corresponding acylsilanes (3).
1. In search of additional support for that conclusion
and as a prelude to future experiments aimed at eluci-
dating the stereochemical course of the rearrangement,
we sought to trap the anion of 1 prior to bond
reorganization.
In their own studies on the mechanism and synthetic
utility of the Wittig rearrangement, Schlosser and
Strunk3d had developed conditions that allowed virtu-
ally quantitative metalation and subsequent silylation
of allyl ethers with little competition from [1,2]- and/or
[1,4]-rearrangements. Following their lead, we treated
cold (ꢀ75 °C) THF-solutions of 1 with sec-BuLi fol-
lowed after some period of time by chlorotrimethyl-
silane (TMSCl) (Scheme 2). Given the short reaction
times (<30 min) we expected to obtain mixtures of silyl-
enol ether 4 and bissilane 5. However, 5 was never ob-
served. Even when the reaction was quenched early,
only 41 and unreacted starting material (1) could be
identified in the crude reaction mixtures.
The mechanism by which the [1,4]-Wittig rearrangement
occurs appears to be substrate dependent, with radical/
radical anion dissociation/recombination or concerted
pathways possible.3 For 1, the observed ratio of
[1,4]- to [1,2]-products was reliant on the reaction tem-
perature, with the [1,2]-Wittig rearrangement intruding
at higher temperatures. We interpreted these results as
evidence of a concerted rearrangement of deprotonated
Given these results, the unusually high reaction rate,
and the complete absence of [1,2]-Wittig products,
we had to consider the option that the deprotona-
tion step and the rearrangement of 1 were happening
1'
s-BuLi
Ph
Ph
1'
—
+
O
(1.5 equiv)
O
O
Ph
TMS
E
4
2
4
TMS
THF,
–75 °C,
30 min
TMS
3
E
2
1
3
Scheme 1. [1,4]-Wittig rearrangement of 1.
s
-BuLi
Ph
OTMS
O
Ph
TMS
O
Ph
(1.5 equiv)
+
TMS
TMS
TMS
THF, –75 ºC,
0–30 min;
then TMSCl
Keywords: [1,4]-Wittig rearrangement; Deprotonation; Organosilanes;
Carbanion.
4
5 (not observed)
1
*
Corresponding author. Tel.: +1 517 355 9715; fax: +1 517 353
1793; e-mail: maleczka@chemistry.msu.edu
Scheme 2.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.018

6566
E. N. Onyeozili, R. E. Maleczka, Jr. / Tetrahedron Letters 47 (2006) 6565–6568
simultaneously. Although such a concerted course of
action would be unusual in carbanion chemistry, analo-
gous mechanisms include the widely accepted enzyme
catalyzed depronation/electrophilic capture sequence.4
Ph
OTMS
O
Ph
TMS
TMS
TMS
4 equiv TMSCl,
4
5
4 equiv Et N,
3
O
Ph
TMS
THF, rt;
Ph
O
TMS
O
Of course it was just as likely, if not more, that deproto-
nation and Wittig rearrangement were separate steps,
the former leading to a carbanion intermediate that sim-
ply rearranged prior to the addition of the electrophile.
To test for this possibility, we sought to take advantage
of the relatively slow reaction between TMSCl and
alkyllithiums5 and deprotonate 1 in the presence of
TMSCl. In practice, slowly adding s-BuLi (1.5 equiv as
a 1.3 M solution in cyclohexane added at 1.0 mL/
70 min) to a ꢀ78 °C mixture of 1, TMSCl (4.0 equiv),
and triethylamine (4.0 equiv) in THF, followed by stir-
ring for 1 h at that temperature and then an aqueous
workup, resulted in the isolation of compound 56
(55%) and unreacted starting material (18%) (Scheme
3). The geometry of 5 was ascertained by transient
NOE experiments and is consistent with an intramole-
cular coordination between lithium and the substrate
oxygen.3d,e Similarly, the silylation occurred exclusively
at the c-position, which was consistent with previously
documented reports.3d,7
then
Ph
TMS
2 equiv
s-BuLi,
1
2 h, rt
6
8
7
O
9
TMS
Ph
yields:
TMS
TMS
O
Ph
TMS
TMS
4 + 5 = 6%
6 + 7 = 28% (>4:1)
8 = trace;
TMS
9 = 17%
Scheme 4.
the low temperature reactions to completion (Scheme 3),
compound 1 was reacted with 2.5 equiv of s-BuLi (vs.
1.5 equiv). While excess base did allow for the complete
consumption of starting material, it also gave rise to tris-
silylated byproducts 8 and 9 (see Scheme 4 for struc-
tures). When the s-BuLi was added at approximately
1.0 mL/30 min 5, 8, and 9 were produced in a ratio of
5.9:1.0:2.8 with a combined 66% yield. Even more rapid
addition of the base (>1.0 mL/15 min) increased the for-
mation of 8 and 9 to where they became the major prod-
ucts (5:8:9 1.0:1.1:4.4) (85% combined yield).
These results certainly implied that 1 underwent depro-
tonation followed by a separate rearrangement step.
However, as a final test of this conclusion, we ran a con-
trol experiment where 1 was reacted with 4 equiv
TMSCl and 4 equiv triethylamine in THF at ꢀ78 °C,
without s-BuLi. Under these conditions, no reaction
occurred, ruling out the possibility that Et3N was
deprotonating 1. This negative result, combined with
the in situ trapping experiments described above, and
the absence of any observable Wittig products during
those same experiments are firm indications that the
a-deprotonation and [1,4]-Wittig rearrangement of 1
are not concerted events.
Compounds 8 and 9 could originate from the deproto-
nation of 5. To gauge the likelihood of this option, we
added s-BuLi at ꢁ1.0 mL/40 min to a mixture of
TMSCl, Et3N, and 5. Surprisingly, during each of two
runs 5 reacted very slowly. Analysis of the reactions
after the typical 2 h at ꢀ78 °C revealed only trace
amounts of 8 and 9. Quenching the reaction after 24 h,
gave 85% of 5 along with a 1.0:1.7 mixture of 8 and
9.9 These data argue against 8 and 9 coming exclusively
from 5. Barring aggregate effects or increases in the
heats of mixing, it is also difficult to relate changes in site
selectivity during the deprotonation of 5 with differences
in the s-BuLi addition rate.
As electrophile capture superceded rearrangement at
low temperatures, we next asked what would happen
at elevated temperatures. Thus, the in situ trapping
experiment was repeated at room temperature (Scheme
4). The outcome of this reaction was generation of at
least six compounds. [1,4]- and [1,2]-Derived Wittig
products 68 and 78 (4:1) along with silylated enol ether
41 contributed to over 30% of the reaction’s yield. A tris-
silylated byproduct (96) was also isolated in approxi-
mately 17%, as were small amounts of 5 and a second
trissilylated byproduct (86). As these data clearly showed
rearrangement to be competitive with in situ TMS
trapping at room temperature, the above query was
answered. However, the formation of trissilylated prod-
ucts (8 and 9) raised new questions. In attempts to drive
If 5 is not chiefly responsible for the formation of 8 and
9, then perhaps the dianion of 1 (10), resulting from the
sudden presence of excess s-BuLi is operative. Such a
dianion could afford 9 directly. Though purely conjec-
ture, 8 could arise from a process where silylation of
dianion 10 at the c-position was followed by an intra-
molecular proton shift9 to afford the silyl stabilized allyl
anion (Scheme 5).
While the mechanism by which 8 and 9 originate
remains speculative, any potential dianion formation
under the Wittig conditions would have consequences
for future applications of the reaction. The [1,4]-Wittig
Ph
Ph
H
Ph
4 equiv TMSCl,
4 equiv Et N,
3
O
Ph
TMS
O
Ph
O
TMS
TMSCl
O
TMS
O
TMS
THF, –75 °C;
starting
material (1)
(~18%)
+
1
8
TMS
TMS
then
H
s
-BuLi
TMSCl
1.5 equiv s-BuLi,
5 (55%)
1
10
2 h at –75 °C
TMS
TMS
Scheme 3.
Scheme 5.

E. N. Onyeozili, R. E. Maleczka, Jr. / Tetrahedron Letters 47 (2006) 6565–6568
6567
rearrangement of 1 typically requires 1.5 equiv of base
TMS
TMS
15
to go to completion. Thus, excess base is available for
a second deprotonation. Furthermore if dianion forma-
tion of 1 is relatively facile with excess base, then
increasing the acidity of protons at the migrating center
could make some dianion formation unavoidable even
with only 1.0 equiv of base. Such dianions would be very
sluggish toward rearrangement, thereby limiting sub-
strate scope.
TMS
TMS
O
4 equiv TMSCl,
TMS
α'
4 equiv Et N,
3
THF, –75 °C;
O
TMS
(15/16 = 1:3.4)
then
TMS
α
2 equiv s-BuLi,
TMS
2 h at rt
(81%)
11
O
TMS
16
TMS
To probe this issue further we examined the reaction of
compound 11.10 While the relative acidities of protons at
C-2 and C-10 should be similar,11 mono deprotonation
at either position would generate anionic intermediates
capable of [2,3]-, [1,2]-, or [1,4]-Wittig rearrangement.
Despite multiple Wittig pathways, exposure of 11 to
our normal [1,4]-Wittig conditions showed little evi-
dence of a reaction (Scheme 6, R = TMS). Even at room
temperature, the consumption of starting material was
slow and the product mixture complex.
Scheme 7.
of these experiments, we determined that the presence of
anion stabilizing groups on the migrating substituent
could be detrimental to the success of the reaction.
Studies aimed at determining the role of these substitu-
ent effects (i.e., dianion formation) as well as a broader
survey of the substrate scope are on-going and will be
reported in due course.
This stood in contrast to the reaction of compound 12,10
which with either s-BuLi or n-BuLi underwent facile
[2,3]-Wittig rearrangement followed by TMS group
migration8 to afford 136 and a minor amount (10%) of
its conjugated isomer (146) (Scheme 6, R = Ph). No
[1,2]- or [1,4]-Wittig products were observed during the
reaction of 12. Furthermore, while the isolated yield of
13 and 14 was only 51%; the crude material appeared
to be fairly clean, indicating a very efficient trans-
formation.
Acknowledgements
We thank the NIH (HL-58114), NSF (CHE-9984644),
and the Astellas USA Foundation for their generous
support.
Supplementary data
Experimental details and compound characterization
data are available on-line at http://www.sciencedirect.
com/. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.tetlet.2006.07.018.
We suspected that the key difference between the TMS
(11) and Ph (12) analogues is that 11 has a higher kinetic
acidity11,12 at C-10 and thus is able to form a rearrange-
ment inhibiting dianion. With this in mind, we again
looked to in situ trap the carbanion intermediate(s) gen-
erated during the reaction of 11. Treatment of a ꢀ78 °C
THF solution of 11, 4 equiv TMSCl, and 4 equiv Et3N
with 2 equiv s-BuLi afforded tetrasilylated compounds
156 and 166 (1.0:3.4) in 86% yield after column chroma-
tography on AgNO3-impregnated silica gel13 (Scheme
7). While we cannot rule out stepwise installment of
the TMS groups, these products are consistent with
dianion formation. Irrespective of the mechanistic de-
tails, the different reactivities of 11 and 12 indicate that
the future success of a-alkoxyallylsilanes in [1,4]-Wittig
rearrangements will likely hinge on the relative acidity
of the a and a0 ethereal protons.
References and notes
1. Onyeozili, E. N.; Maleczka, R. E., Jr. Chem. Commun.
2006, 2466–2468.
2. For Wittig rearrangement reviews see: (a) Nakai, T.;
Mikami, K. Org. React. 1994, 46, 105–209; (b) Tomooka,
K.. In Chemistry of Organolithium Compounds; Rappo-
port, Z., Ilan, M., Eds.; Wiley: London, 2004; Vol. 2, pp
749–828.
3. (a) Felkin, H.; Frajerman, C. Tetrahedron Lett. 1977, 18,
3485–3488, and references cited therein; (b) Sayo, N.;
Kimura, Y.; Nakai, T. Tetrahedron Lett. 1982, 23, 3931–
3934; (c) Hayakawa, K.; Hayashida, A.; Kanematsu, K. J.
Chem. Soc., Chem. Commun. 1988, 1108–1110; (d) Schlo¨s-
ser, M.; Strunk, S. Tetrahedron 1989, 45, 2649–2664; (e)
Nakazaki, A.; Nakai, T.; Tomooka, K. Angew. Chem., Int.
Ed. 2006, 45, 2235–2238.
In conclusion, through the in situ trapping of the carb-
anion intermediate, we have shown that deprotonation
and [1,4]-Wittig rearrangement of a-alkoxysilanes are
not concerted but rather separate events. As an outgrowth
4. Gerlt, J. A.; Gassman, P. G. J. Am. Chem. Soc. 1992, 114,
5928–5934.
5. Bey, A. E.; Weyenberg, D. R. J. Org. Chem. 1966, 31,
2036–2037.
1'
3'
BuLi
TMS
+
O
TMS
O
(1.5 equiv)
R
O
2
3'
3'
Me
2
2
6. The structure assigned to each new compound is in accord
THF,
–78 °C,
2.5 h
TMS
1
with its IR, H NMR and 13C NMR spectra, as well as
R
R
13
14
11 (R = TMS)
12 (R = Ph)
appropriate parent ion identification by HRMS. See
Supplementary data for additional details.
R = TMS: no Wittig
R = Ph: 51% (10:1)
7. Murai, A.; Abiko, A.; Shimada, N.; Masamune, T.
Tetrahedron Lett. 1984, 25, 4951–4954.
Scheme 6.

6568
E. N. Onyeozili, R. E. Maleczka, Jr. / Tetrahedron Letters 47 (2006) 6565–6568
8. Maleczka, R. E., Jr.; Geng, F. Org. Lett. 1999, 1, 1115–
11. For the deprotonation and rearrangement of vinylogous
a-alkoxysilanes see: (a) Mikami, K.; Kishi, N.; Nakai, T.
Chem. Lett. 1989, 1683–1686; (b) Greeves, N.; Lee, W.-M.
Tetrahedron Lett. 1997, 38, 6445–6448.
12. It is difficult to estimate the pK differences between 11 and
12, but intrinsic silyl stabilization is said to be worth about
2–3 pK units for delocalized carbon acids. See Streitwieser,
A.; Xie, L.; Wang, P.; Bachrach, S. M. J. Org. Chem.
1993, 58, 1778–1784.
1118.
9. We are tempted to speculate that the minimization of A1,2
-
strain within 5 accounts for the seemingly slow intermo-
lecular deprotonation of the allylic protons.
10. Compounds 11 (46% (Lewis acid = BF3ÆEt2O)) and 12
(17% (Lewis acid = TMSOTf)) were generated from the
corresponding trichloroacetimidate as generally described
in Maleczka, R. E., Jr.; Geng, F. Org. Lett. 1999, 1, 1111–
1113 and the Supplementary data.
13. Lawrence, B. M. J. Chromatogr. A 1968, 38, 535–537.