Efficient approach to 3,3-bissilyl carbonyl and enol derivatives via retro-[1,4] brook rearrangement of 3-silyl allyloxysilanes

Article abstract of DOI:10.1021/ol102352w

A facile and highly stereoselective retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes has been discovered. While basic hydrolysis of the formed (Z)-3,3-bissilyl lithium enolates provides 3,3-bissilyl carbonyl compounds efficiently, trapping the species with various electrophiles including alkyl halides leads to the exclusive O-substituted (Z)-3,3-bissilyl enol derivatives that can undergo a Sakurai reaction with aldehyde to produce the synthetically useful 1,2-diol diastereoselectively.

Full text of DOI:10.1021/ol102352w

ORGANIC
LETTERS
2010
Vol. 12, No. 22
5298-5301
Efficient Approach to 3,3-Bissilyl
Carbonyl and Enol Derivatives via
Retro-[1,4] Brook Rearrangement of
3-Silyl Allyloxysilanes
Zhenlei Song,*,†,‡,§ Zheng Lei,† Lu Gao,† Xia Wu,† and Linjie Li†
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal
Chemistry, West China School of Pharmacy, and State Key Laboratory of Biotherapy,
West China Hospital, Sichuan UniVersity, Chengdu, 610041, P. R. China, and State
Key Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, Lanzhou 730000, China
zhenleisong@scu.edu.cn
Received September 30, 2010
ABSTRACT
A facile and highly stereoselective retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes has been discovered. While basic hydrolysis of
the formed (Z)-3,3-bissilyl lithium enolates provides 3,3-bissilyl carbonyl compounds efficiently, trapping the species with various electrophiles
including alkyl halides leads to the exclusive O-substituted (Z)-3,3-bissilyl enol derivatives that can undergo a Sakurai reaction with aldehyde
to produce the synthetically useful 1,2-diol diastereoselectively.
Retro-Brook rearrangement,1 describing an intramolecular
silyl migration from an oxygen to a carbon atom,
comprises a powerful tactic for the rapid construction of
functionalized organosilanes from more accessible silyl
ethers. While many investigations of the retro-[1,4] Brook
rearrangement2 have been reported, only two papers have
appeared describing the process in allyloxysilane systems.
Mitchell3 first reported a lithium amide-induced retro-[1,4]
Brook rearrangement of allyloxysilanes bearing two
organometal residues on the vinylic carbons. However,
as the author mentioned, the silyl migration is only feasible
when the trimethylsilyl group was involved due to the
steric effect at silicon. Recently, Tomooka4 investigated
the retro-[1,4] Brook rearrangement of simple allyloxysi-
lanes. The stereochemical course was clarified for the first
time by using a silicon-centered chiral silyl group as the
migration moiety.
† West China School of Pharmacy, Sichuan University.
‡ West China Hospital, Sichuan University.
§ Lanzhou University.
(1) For reviews, see: (a) West, R. In AdVances in Organometallic
Chemistry; West, R., Stone, F. G. A., Eds.; Academic Press: New York,
1977; Vol. 16, pp 1-31. (b) 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. (c) Clayden, J. In Organo-
lithiums: SelectiVity for Synthesis; Clayden, J., Ed.; Pergamon: Oxford, 2002;
pp 340-346. (d) Tomooka, K. In The Chemistry of Organolithium
Compounds; Rappoport, Z., Marek, I., Ed.; Wiley: Chichester, 2004; Vol.
2, pp 749-828.
The starting point of this work arises from our interest in
geminal bimetallic species, which are useful building blocks
and have shown high efficiency in the selective formation
10.1021/ol102352w  2010 American Chemical Society
Published on Web 10/28/2010

of carbon-carbon bonds.5 Our particular attention is cur-
rently focused on a special type of geminal bissilyl com-
pounds6 such as 3,3-bissilyl carbonyl and enol derivatives 5
and 6. Despite potentially being attractive synthons, they have
been barely investigated due to the lack of suitable synthetic
methods. We envisioned that a direct and practical entry into
these species might be achieved via the retro-[1,4] Brook
rearrangement of 3-silyl allyloxysilanes 1 (Scheme 1).
Herein, we report the realization of this methodology.
HMPA as cosolvent was also not effective and led to less
than 40% conversion. Delightfully, when s-BuLi was used
instead of t-BuLi, 1a was consumed completely in several
seconds at -78 °C and converted into a new compound after
quenching with 10% aq HCl (Scheme 2). To our surprise,
Scheme 2a
Scheme 1
a a. LDA (1.5 equiv), THF, -78 °C to rt. b. t-BuLi (1.5 equiv), HMPA
(5.0 equiv)/THF, -78 °C. c. s-BuLi (1.5 equiv), HMPA (5.0 equiv)/THF,
-78 °C then 10% aq HCl. d. further hydrolysis during concentration and
chromatography.
this initial formed product appears to be quite stable with
the acidic hydrolysis condition even for several hours, but it
can be converted slowly into the desired aldehyde 5a during
concentration and chromatography on silica gel. Since the
compound has been ruled out to be either retro-[1,2] Brook
rearrangement or 1,3-hydrogen shift products, we presumed
it might be the hydrate 7 generated by hydrolysis of the
lithium enolate intermediate 4.
Given the observed good acid stability of 7, we predicted
basic hydrolysis would be feasible to generate the desired
aldehydes. As expected, quenching the reaction with 10 equiv
of H2O followed by stirring at room temperature for 3 h gave
rise to the aldehyde 5a in 62% yield (Table 1, entry 1). It is
In accordance with Mitchell’s observation, the initial use
of LDA as base proved to be unworkable for the rearrange-
ment of 1a possessing the sterically hindered triethylsilyl
groups. Tomooka’s protocol using t-BuLi with 5.0 equiv of
(2) For studies on the retro-[1,4] Brook rearrangement, see: (a) Evans,
D. A.; Takacs, I. M.; Hurst, K. M. J. Am. Chem. Soc. 1979, 101, 371. (b)
Rucker, C. Tetrahedron Lett. 1984, 25, 4349. (c) Mora, J.; Costa, A.
Tetrahedron Lett. 1984, 25, 3493. (d) Lautens, M.; Delanghe, P. H. M.;
Goh, J. B.; Zhang, C. H. J. Org. Chem. 1992, 57, 3270. (e) Marumoto, S.;
Kuwajima, I. J. Am. Chem. Soc. 1993, 115, 9021. (f) Jiang, X. L.; Bailey,
W. F. Organometallics 1995, 14, 5704. (g) Braun, M.; Mahler, H. Liebigs
Ann. 1995, 29. (h) Bures, E.; Spinazze, P. G.; Beese, G.; Hunt, I. R.; Rogers,
C.; Keay, B. A. J. Org. Chem. 1997, 62, 8741. (i) Bousbaa, J.; Ooms, F.;
Krief, A. Tetrahedron Lett. 1997, 38, 7625. (j) Gibson, C.; Buck, T.; Walker,
M.; Bru¨eckner, R. Synlett 1998, 201. (k) Kleinfeld, S. H.; Wegelius, E.;
Hoppe, D. HelV. Chim. Acta 1999, 82, 2413. (l) Comanita, B. M.; Woo,
S.; Fallis, A. G. Tetrahedron Lett. 1999, 40, 5283. (m) Simpkins, S. M. E.;
Kariuki, B. M.; Arico, C. S.; Cox, L. R. Org. Lett. 2003, 5, 3971. (n) Nahm,
M. R.; Xin, L. H.; Potnick, J. R.; Yates, C. M.; White, P. S.; Johnson, J. S.
Angew. Chem., Int. Ed. 2005, 44, 2377. (o) Yamago, S.; Fujita, K.; Miyoshi,
M.; Kotani, M.; Yoshida, J. Org. Lett. 2005, 7, 909. (p) Mori, H.; Matsuo,
T.; Yoshioka, Y.; Katsumura, S. J. Org. Chem. 2006, 71, 9004. (q) Mori,
Y.; Futamura, Y.; Horisaki, K. Angew. Chem., Int. Ed. 2008, 47, 1091.
(3) (a) Mitchell, T. N.; Schu¨tze, M.; Giebelmann, F. Synlett 1997, 187.
(b) Mitchell, T. N.; Schu¨tze, M. Tetrahedron 1999, 55, 1285.
Table 1. Screening of Reaction Conditions
entry
HMPA
workup
tempa time yieldb
1
2
3
4
5.0 equiv
1.2 equiv H2O (10 equiv)
0.3 equiv
1.2 equiv
H2O (10 equiv)
rt
rt
rt
50°C
3 h
3 h
3 h
1 h
62%
91%
N.D.
30%
(4) Nakazaki, A.; Nakai, T.; Tomooka, K. Angew. Chem., Int. Ed. 2006,
45, 2235.
(5) For reviews, see: (a) Marek, I.; Normant, J. F. Chem. ReV. 1996,
96, 3241. (b) Marshall, J. A. Chem. ReV. 1996, 96, 31. (c) Marek, I. Chem.
ReV. 2000, 100, 2887. (c) For recent advances, see: Shimizu, M.; Kitagawa,
H.; Kurahashi, T.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 4283. (d)
Hirashita, T.; Hayashi, Y.; Mitsui, K.; Araki, S. J. Org. Chem. 2003, 68,
3467, and references therein.
H2O (10 equiv)
H2O (10 equiv)
LiOH (3 equiv)/H2O
(20 equiv)
5
1.2 equiv
rt
2 h
75%
a Temperature of the basic hydrolysis step. b Isolated yields after
(6) For studies on geminal bissilyl species, see: (a) Fleming, I.; Floyd,
C. D. J. Chem. Soc., Perkin Trans. 1 1981, 969. (b) Ahlbrecht, H.; Farnung,
W.; Simon, H. Chem. Ber. 1984, 117, 2622. (c) Brook, A. G.; Chrusciel,
J. J. Organometallics 1984, 3, 1317. (d) Klumpp, G. W.; Mierop, A. J. C.;
Vrielink, J. J.; Brugman, A.; Schakel, M. J. Am. Chem. Soc. 1985, 107,
6740. (e) Lautens, M.; Ben, R. N.; Delanghe, P. H. M. Angew. Chem., Int.
Ed. 1994, 33, 2448. (f) Lautens, M.; Delanghe, P. H. M.; Goh, J. B.; Zhang,
C. H. J. Org. Chem. 1995, 60, 4213. (g) Lautens, M.; Ben, R. N.; Delanghe,
P. H. M. Tetrahedron 1996, 52, 7221. (h) Princet, B.; Anselme, G.; Pornet,
J. Synth. Commun. 1999, 29, 3326. (i) Princet, B.; Gariglio, H. G.; Pornet,
J. J. Organomet. Chem. 2000, 604, 186. (j) Hodgson, D. M.; Barker, S. F.;
Mace, L. H.; Moran, J. R. Chem. Commun. 2001, 153. (k) Onyeozili, E. N.;
Maleczka, R. E. Tetrahedron Lett. 2006, 47, 6565. (l) Williams, D. R.;
purification by silica gel column chromatography.
noteworthy that despite that Tomooka has emphasized the
importance of a large excess of HMPA for the high
selectivity of retro-[1,4] Brook rearrangement in simple
allyloxysilane systems4 here 1.2 equiv appeared to be
effective enough to facilitate the silyl migration, providing
an even much higher 91% yield (entry 2). However, using a
catalytic amount of HMPA only resulted in the partial retro-
´
Morales-Ramos, A. I.; Williams, C. M. Org. Lett. 2006, 8, 4393.
Org. Lett., Vol. 12, No. 22, 2010
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[1,2] Brook rearrangement, and no retro-[1,4] one occurred
(entry 3). More vigorous workup conditions including stirring
at 50 °C (entry 4) or adding an extra 3.0 equiv of LiOH
(entry 5) led to the faster hydrolysis, but the yields dramati-
cally decreased.
Table 3. Reactions with Electrophiles
Having established the optimal reaction conditions, we
further examined the scope of substrates. Not limited to (E)-
3-silyl allyloxysilane, 1a with Z-configuration is also suitable,
giving the comparably high yield (Table 2, entry 1).
Table 2. Scope of 3-Silyl Allyloxysilanes
a Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv),
HMPA (1.2 equiv) in THF at -78 °C, then H2O (10 equiv), warmed to rt,
3 h. b Isolated yields after purification by silica gel column chromatography.
c TMEDA (1.5 equiv) was added.
Moreover, a wide range of silyl groups were found capable
to undergo the smooth migration, even though the formed
bissilyl moieties are much hindered (entries 2-6). Formation
of the aldehyde 5g (entry 7), in which the migrated silyl
group contains an allyl substitution, presents a more attractive
result given the potential of further intramolecular transfor-
mations. Reactions of 3-silyl allyloxysilanes bearing substitu-
tion at the 1- or 2-position can also proceed successfully
when the more reactive s-BuLi/TMEDA complex was used
to facilitate the deprotonation step (entries 8-10). However,
with substitution and even the anion-stabilizing phenyl group,
located at the 3-position, the silyl migration was totally
suppressed probably due to the difficulty of forming the
sterically constrained 3-quaternary carbon.
a Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv),
HMPA (1.2 equiv) in THF at -78 °C, then R3X (3.0 equiv), warmed to rt,
4 h. b The stereoselectivity was determined by 1H NMR spectroscopy, and
the configuration was determined by NOE experiments of 6f. c Isolated yields
after purification by silica gel column chromatography. d TMEDA (1.5
equiv) was added.
Reactions quenched with various electrophiles were further
examined by using allyloxysilane 1a as the model substrate.
As summarized in Table 3, reactions with trialkylsilyl
chlorides (Table 3, entry 1) and acyl chlorides (entries 2-5)
provided the corresponding functionalized 3,3-bissilyl enol
derivatives smoothly and in good to excellent yields.
Generation of the exclusive (Z)-configuration supports
formation of the five-membered pentacoordinated silicate 37
to be reasonable during the course. The particularly notable
results were obtained when alkyl halides were used as
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Org. Lett., Vol. 12, No. 22, 2010

electrophiles (entries 6-12). All reactions present the reliable
and exclusive O-alkylated selectivity, and no C-alkylated
products were detected at all. This result is in sharp contrast
to the previous observations by Still8 and Tomooka4 since
they have all found that quenching reactions of simple
allyloxysilanes with iodomethane only provided the γ-C-
alkylated product,s and none of the retro-Brook rearranged
products were formed.
oxygen anion completely with generating the exclusive
O-alkylated products.
The wide existence of polyketide natural products then
led us to explore the allylation reactivity of 3,3-bissilyl enol
derivatives with aldehydes. The preliminary result is shown
in Scheme 4. By treatment of silyl enol ether 6m with TiCl4
Rationalization of this excellent O-alkylated selectivity is
proposed as follows. Given the coupling constant (J ) 12.4
Hz) of H2 and H3 in 6f as well as no NOE being observed
between them, we speculated the most favorable conforma-
tion of lithium enolate could be expected as 4a that involves
the minimum allylic strain and nonbonded interaction
(Scheme 3). Thus, regeneration of the pentacoordinated
Scheme 4
and n-butanal, an expected Sakurai reaction,5b,9 rather than
Mukaiyama aldol addition, occurred to give 1,2-diol 11 in
48% yield and as a single (E)-anti-isomer.10
Scheme 3
We have described a facile and highly stereoselective retro-
[1,4] Brook rearrangement of 3-silyl allyloxysilanes. This
route provides a practical entry to a diverse array of 3,3-
bissilyl carbonyl and enol derivatives. The synthetic values
of these building blocks have also been demonstrated by the
Sakurai reaction with aldehyde to generate the 1,2-diol
diastereoselectively. Detailed studies on the rearrangement
and other applications of this methodology are currently
underway.
Acknowledgment. This research was supported by the
National Natural Science Foundation of China (20802044,
21021001), the National Basic Research Program of China
(973 Program, 2010CB833200), and RFDP (200806101091).
The authors also thank Prof. Richard P. Hsung (UW,
Madison) for invaluable discussions.
silicate 3a and allylic anion 2a via a reverse process would
be quite difficult, thereby prohibiting C-alkylation at the 1-
and 3-position to give 8 and 9, respectively. In fact, we have
found that the whole silyl migration proceeded very fast;
moreover, 4a can be stored at either -78 or 10 °C for several
hours while still maintaining the good reactivity with
electrophiles. That is to say, formation of 4a is both a kinetic
and a thermodynamic process. On the other hand, due to
the bulky bissilyl moiety shields, both sides of 2-position in
4a, C-alkylation to give aldehyde 10 would be unfeasible,
as well. As a result, alkyl halides are forced to approach the
Supporting Information Available: Experimental pro-
cedures and spectral data for products. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL102352W
(9) (a) Marko´, I. E.; Leroy, B. Tetrahedron Lett. 2000, 41, 7225. (b)
Leroy, B.; Marko´, I. E. Tetrahedron Lett. 2001, 42, 8685. (c) Marko´, I. E.;
Dumeunier, R.; Leclercq, C.; Leroy, B.; Plancher, J. M.; Mekhalfia, A.;
Bayston, D. J. Synthesis 2002, 7, 958. (d) Leroy, B.; Marko´, I. E. Org.
Lett. 2002, 4, 47. (e) Leroy, B.; Marko´, I. E. J. Org. Chem. 2002, 67, 8744.
(f) Dubost, C.; Leroy, B.; Marko´, I. E.; Tinant, B.; Declercq, J. P.; Bryans,
J. Tetrahedron 2004, 60, 7693. (g) Dubost, C.; Marko´, I. E.; Ryckmans, T.
Org. Lett. 2006, 8, 5137. (h) Redpath, P.; Macdonald, S.; Migaud, M. E.
(7) For representative studies, see: (a) Wright, A.; West, R. J. Am. Chem.
Soc. 1974, 96, 3227. (b) Couzijn, E. P. A.; Schakel, M.; de Kanter, F. J. J.;
Ehlers, A. W.; Lutz, M.; Spek, A. L.; Lammertsma, K. Angew. Chem., Int.
Ed. 2004, 43, 3440, and references therein.
(8) (a) Still, W. C.; Macdonald, T. L. J. Am. Chem. Soc. 1974, 96, 5561.
(b) Still, W. C. J. Org. Chem. 1976, 41, 3063. (c) Still, W. C.; Macdonald,
T. L. J. Org. Chem. 1976, 41, 3621. (d) Hosomi, A.; Hashimoto, H.; Sakurai,
H. J. Org. Chem. 1978, 43, 2551. (e) Lau, P.W. K.; Chan, T. H. J.
Organomet. Chem. 1979, 179, C24.
Org. Lett. 2008, 10, 3323
.
(10) The stereochemistry of 11 was determined by NOE experiments
of its acetonide. See the Supporting Information for details.
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