Asymmetric retro-[1,4] brook rearrangement and its stereochemical course at silicon

Article abstract of DOI:10.1002/anie.200503734

(Chemical Equation Presented) Taking the silyl group a step further: An unprecedented rearrangement in an anion derived from an allyloxysilane occurs by a [1,4] shift of the silyl group (see scheme). The asymmetric synthesis of enantiomerically enriched γ

Full text of DOI:10.1002/anie.200503734

Angewandte
Chemie
Asymmetric Rearrangement
DOI: 10.1002/anie.200503734
Asymmetric Retro-[1,4] Brook Rearrangement
and Its Stereochemical Course at Silicon**
Atsuo Nakazaki, Takeshi Nakai, and
Katsuhiko Tomooka*
The trialkylsilyl group shift from the oxygen atom of a silyl
ether to a carbanion terminus—the retro-Brook rearrange-
ment—is useful for the preparation of functionalized organo-
[*] Dr. A. Nakazaki, Prof. Dr. T. Nakai, Prof. Dr. K. Tomooka
Department of Applied Chemistry
Graduate School of Science and Engineering
Tokyo Institute of Technology
Meguro-ku, Tokyo 152-8552 (Japan)
Fax: (+81)3-5734-3931
E-mail: ktomooka@apc.titech.ac.jp
[**] This research was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (A) “Creation of Biologically Functional
Molecules”, Basic Area (B) No. 14350473, Exploratory Research
No. 17655038, and the 21st Century COE Program“Creation of
Molecular Diversity and Development of Functionalities” from the
Ministry of Education, Culture, Sports, Science, and Technology,
Japan. The authors thank Dr. Kazunobu Igawa and Tomohiro
Shimono for helpful discussions and technical assistance.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or fromthe author.
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silanes.[1] Among numerous variants, the rearrangement of an
butyldimethylsilyl trifluoromethanesulfonate (tBuMe2SiOTf)
as an electrophile, the [1,4] rearrangement product 3b[4] (E =
tBuMe2Si) was formed in 25% yield with excellent Z selec-
tivity, along with the [1,2] product 2b (E = tBuMe2Si) in 45%
yield (Table 1, entry 2). Furthermore, addition of hexame-
thylphosphoramide (HMPA) as a cosolvent improves the
[1,4] selectivity and suppresses the formation of the usual
[1,2] product completely (Table 1, entry 3).[5]
allyloxysilane system is one of the most attractive because of
the great synthetic potential of the resultant allylsilanes.[2] In
addition to the normal [1,2] shift, a [1,4] shift is possible in this
particular system [Eq. (1)]. To the best of our knowledge,
however, the [1,4] rearrangement leading to a g-alkoxyallyl-
silane system has remained elusive.[3]
This highly electrophile- and solvent-dependent perise-
lectivity suggested that the rearrangement would be rever-
sible, and that its product distribution might be determined at
the stage of enolate trapping, although the exact origin of the
product changeover is not clear at present.[6] Notably, a
reaction in THF/HMPA quenched with iodomethane pro-
=
vides (Z)-Et3SiOCH CHCH2Me exclusively, and none of the
retro-Brook rearrangement products was formed; this finding
is consistent with the results of Still and Macdonald.[3a] Under
the optimized conditions using HMPA and tBuMe2SiOTf,
allyloxysilanes with bulkier silyl groups undergo selective
retro-[1,4] rearrangement to give 3 in high yields. For
example, the reaction of tBuPh2Si ether 1b or PhtBu(OMe)Si
ether 1c gave the [1,4] products (Z)-3c and (Z)-3d as the sole
products in 95 and 72% yields, respectively. At this stage, we
became aware that the effect of an electrophile on the
periselectivity becomes negligible as long as tBuPh2Si or
PhtBu(OMe)Si is used as the migrating group. For example,
not only tBuMe2SiOTf but also Et3SiCl, MeOCOCl, and
iPr2NCOCl gave the retro-[1,4] Brook rearrangement prod-
ucts 3e–h in moderate to high yields (Table 1, entries 6–9).
Moreover, PhtBu(OMe)Si ethers 4 with various substitution
patterns in the allyl moiety were smoothly converted into the
corresponding retro-[1,4] Brook rearrangement products 5
(Table 2). It is particularly noticeable that the resulting
double bonds are formed with high stereoselectivity
(Table 2, entries 1–4).
Herein, we report the retro-[1,4] Brook rearrangement of
a simple allyloxysilane, in which the judicious choice of
electrophile (E), solvent system, and migrating silyl group
(R3Si) enables this unprecedented [1,4] periselectivity. Of
particular note is the stereospecificity of this process, which
has been unequivocally determined by using an enantiomer-
ically pure allyloxysilane with a silicon stereocenter [Eq. (2)].
Asymmetric synthesis of g-functionalized allylsilanes with a
stereogenic Si-center is accomplished with this retro-[1,4]
Brook rearrangement.
Initial experiments focused on the retro-[1,4] Brook
rearrangement of the simple allyloxysilane 1a with tBuLi in
THF. When the reaction was quenched with chlorotrimethyl-
silane as an electrophile, the [1,2] product 2a (E = Me3Si) was
obtained exclusively; this result is consistent with the claim of
Chan and Lau that no [1,4] product 3a (E = Me3Si) was
formed (Table 1, entry 1).[3c] In sharp contrast, with tert-
Furthermore, moderate to good diastereoselectivities
were observed in the case of a g-substituted system (R3 ¼
H) (Table 2, entries 3 and 4).[7] Although the stereoselectivity
did not reach a practically useful level, these reactions are
rare examples of asymmetric induction from Si* to C*.[8–10]
Our attention was next directed toward
the stereochemical course at the migrating
Table 1: Rearrangement of allyloxysilane 1.
silicon center, which has been a fundamen-
tal but unsettled problem of the retro-
Brook rearrangement.[11–13] To gain a defin-
itive answer to the question, we chose the
Entry
Substrate
R3Si
E
2
Yield [%][a]
3
Yield [%][a]
enantiomerically defined chiral allyloxysi-
lane (S)-1c as substrate, which was readily
available from our previously developed
[1,4]-aryl migration reaction.[14,15] Rear-
rangement product 3d derived from (S)-1c
(> 95% ee) obtained with > 95% ee by
chiral HPLC analysis, which clearly shows
that the rearrangement proceeds in a ste-
reospecific manner at the migrating silicon
center (Scheme 1).[16]
1
2
1a
1a
1a
1b
1c
1b
1c
1c
1c
Et3Si
Et3Si
Et3Si
tBuPh2Si
PhtBu(OMe)Si
tBuPh2Si
PhtBu(OMe)Si
PhtBu(OMe)Si
PhtBu(OMe)Si
Me3Si[d]
2a
2b
2b
2c
2d
2e
2 f
85
45
3a
3b
3b
3c
3d
3e
3 f
n.d.
25
56
95
72
tBuMe2Si[e]
tBuMe2Si[e]
tBuMe2Si[e]
tBuMe2Si[e]
Et3Si[d]
3[b]
4[b]
5[b]
6[b,c]
7[b,c]
8[b]
9[b,c]
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
98
81
Et3Si[d]
MeOCO[d]
iPr2NCO[d]
2g
2h
3g
3h
96
50 [d]
[a] Yields of isolated products; n.d.=not detected by 1H NMR spectroscopy or TLC analyses.
[b] Reaction performed with 4.5 equiv of HMPA. [c] Reaction performed at À78!08C. [d] b-
Silylpropanal (fromhydrolysis of 3h) was obtained as a by-product in 11% yield. [e] Reacted as the
chloride salt. [f] Reacted as the triflate salt.
To determine whether this reaction
proceeds with retention or inversion with
respect to the configuration of the silicon
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Chemie
Table 2: Rearrangement of allyloxysilane 4.
Entry Substrate R1
R2
R3
R3Si
Yield [%][c] d.r.[d]
silicon atom. The silyl group then eliminates the oxygen
1
2
3
4
4a
4b
4c
4d
Me
H
H
H
Me
H
H
H
Me
tBuMe2Si
Et3Si
tBuMe2Si
69
80
10
72
–
–
through a five-membered transition state or intermediate
II[20,21] with the least motion; thus, the configuration of the
silicon center was retained without racemization.
83:17
66:34
H
H
Me3Si tBuMe2Si
[a] tBuMe2SiOTf or Et3SiCl. [b] Geometrical purities are >98%. [c] Yields
of isolated products. [d] Stereoisomers over the silicon stereocenter and
the adjacent stereogenic carbon center in 5. d.r.=diastereomeric ratio.
In summary, we have described an unprecedented exam-
ple of retro-[1,4] Brook rearrangement in an allyloxysilane
system, the stereochemical course of which was clarified for
the first time. The reaction provides not only synthetically
attractive allylsilanes, but it also serves as a stereospecific
approach to multifunctionalized chiral silanes. A detailed
mechanistic study of the rearrangement and asymmetric
synthesis using Si stereocenters is in progress.
Received: October 21, 2005
Revised: December 16, 2005
Published online: March 3, 2006
Keywords: asymmetric synthesis · chirality · rearrangement ·
.
silanes
Scheme 1. Rearrangement of allyloxysilane (S)-1c. a) tBuLi, THF,
HMPA, À788C; then tBuMe2SiOTf, À78!08C, 72% (>95% Z,
>95% ee); b) tBuLi, THF, HMPA, À788C; then 6, À78!08C, 66%
(d.r.=>95:<5). Tf=trifluoromethanesulfonyl.
[1] For reviews, see: a) R. West in Advances in Organometallic
Chemistry, Vol. 16 (Eds.: F. G. A. Stone, R. West), Academic
Press, New York, 1977, pp. 1 – 31; b) A. G. Brook, A. R. Bassin-
dale in Rearrangements in Ground and Excited States, Vol. 2
(Ed.: P. de Mayo), Academic Press, New York, 1980, pp. 149 –
227; c) K. Tomooka in The Chemistry of Organolithium Com-
pounds, Vol. 2 (Eds.: Z. Rappoport, I. Marek), Wiley, Chi-
chester, 2004, pp. 749 – 828.
[2] For reviews, see: a) I. Fleming, A. Barbero, W. Walter, Chem.
Rev. 1997, 97, 2063 – 2192; b) A. Hosomi, K. Miura, Bull. Chem.
Soc. Jpn. 2004, 77, 835 – 851; c) L. Chabaud, P. James, Y. Landais,
Eur. J. Org. Chem. 2004, 3173 – 3199.
center, we prepared 7 by trapping the lithium enolate with an
enantiomerically pure sultam derivative 6,[17] and a single-
crystal X-ray diffraction study of 7 was performed.[18] As
shown in Figure 1, the absolute configuration of the silicon
center has been determined as the R configuration on the
[3] For representative studies on retro-[1,2] Brook rearrangement,
see: a) W. C. Still, T. L. Macdonald, J. Am. Chem. Soc. 1974, 96,
5561 – 5563; b) A. Hosomi, H. Hashimoto, H. Sakurai, J. Org.
Chem. 1978, 43, 2551 – 2552; c) P. W. K. Lau, T. H. Chan, J.
Organomet. Chem. 1979, 179, C24 – C28.
[4] The structure of 3b was confirmed by conversion to the
corresponding b-silyl propinaldehyde by acidic hydrolysis. The
details are given in the Supporting Information.
[5] A large excess of HMPA is important for high [1,4] selectivity.
Indeed, a reaction with 1 equivof HMPA provides [1,4] product
3b in 38% yield, along with [1,2] product 2b in 8% yield.
[6] Coordination of an electrophile or solvent to the lithium ion
might affect the reactivity of the allylic anion. Further work,
including NMR and IR analyses of the intermediate, is under
way to elucidate the reaction mechanism.
Figure 1. Molecular structure of 7 in the solid state. Hydrogen atoms
have been omitted for clarity. The thermal ellipsoid probabilities are
shown at 50%.
[7] The relative configuration has not been determined.
[8] For reviews of asymmetric synthesis based on silicon stereocen-
ters, see: a) T. H. Chan, D. Wang, Chem. Rev. 1992, 92, 995 –
1006; b) S. Bienz, Chimia 1997, 51, 133 – 139; c) M. Oestreich,
Chem. Eur. J. 2006, 12, 30 – 37.
[9] For representative studies on chirality transfer from silicon to
carbon, see: intramolecular version: a) D. R. Schmidt, S. J.
OꢀMalley, J. L. Leighton, J. Am. Chem. Soc. 2003, 125, 1190 –
basis of the known chirality of sultam, which indicates that
this novel retro-[1,4] Brook rearrangement proceeds via
retention of configuration at the silicon center.
A plausible mechanism of this rearrangement is shown in
Equation (3). Deprotonation of the allyloxysilane in a-
position by tBuLi gives allyloxy anion I in cisoid form owing
[19]
À
to the Li O coordination,
and the g carbon attacks the
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Communications
1191; intermolecular version: b) M. Oestreich, S. Rendler,
Angew. Chem. 2005, 117, 1688 – 1691; Angew. Chem. Int. Ed.
2005, 44, 1661 – 1664, and references therein.
À
[10] We also attempted to form a C C bond by the reaction of the
lithium enolate with a carbon electrophile. Thus, silane 4a was
treated successively with tBuLi and iodomethane to afford the
expected product 8 in 65% yield (d.r. = 66:34) [Eq. (4)].
[11] The stereochemical course of the nucleophilic substitution on
the silicon center has been investigated in various systems; it
strongly depends on the leaving groups. a) L. H. Sommer in
Stereochemistry, Mechanism and Silicon, McGraw-Hill, New
York, 1965; b) L. H. Sommer, Intra-Sci. Chem. Rep. 1973, 7, 1 –
44.
[12] The stereochemical course of the retro-[1,2] Brook rearrange-
ment at a lithiated carbanion center has been investigated. For
inversion of configuration at the benzylic anion, see: a) A.
Wright, R. West, J. Am. Chem. Soc. 1974, 96, 3227 – 3232; for
retention of configuration at the aliphatic anion, see: b) R. J.
Linderman, A. Ghannam, J. Am. Chem. Soc. 1990, 112, 2392 –
2398.
[13] Ab initio calculations have shown that the configuration at the
silicon center is retained in retro-[1,2] Brook rearrangements. Y.
Wang, M. Dolg, Tetrahedron 1999, 55, 12751 – 12756.
[14] K. Tomooka, A. Nakazaki, T. Nakai, J. Am. Chem. Soc. 2000,
122, 408 – 409.
[15] Allyloxysilane (S)-1c was prepared from (S)-3-hydroxypyrroli-
din-2-one in six steps. Details are given in the Supporting
Information.
[16] The enantiomeric excess of (R)-3d was determined by chiral
HPLC analysis of its derivative 9: Chiralcel OD (4.6 ” 250 mm),
hexane/2-propanol (10:1), 0.5 mLminÀ1, UV/Vis detection at l =
254 nm, room temperature; tR = 11.8 min for R-isomer, 14.2 min
for S-isomer. DIBAL = diisobutyl aluminium hydride [Eq. (5)].
[17] Newly developed sultam derivative 6 was prepared from S-(À)-
sultam, p-nitrobenzoyl chloride, and Et3N in 78% yield.
[18] CCDC-277991 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[19] For the formation of Z-vinyl ether from allyl ether via the cisoid
allylic anion, see: a) M. Schlosser, S. Strunk, Tetrahedron 1989,
45, 2649 – 2664; b) A. R. Katritzky, M. Piffl, H. Lang, E. Anders,
Chem. Rev. 1999, 99, 665 – 722, and reference [3a].
[20] Wright and West have proposed pentacoordinated silicon as a
reasonable intermediate for the retro-[1,2] Brook rearrange-
ment. See reference [12a].
[21] Recently, a pentaorganosilicate has been reported: E. P. A.
Couzijn, M. Schakel, F. J. J. de Kanter, A. W. Ehlers, M. Lutz,
A. L. Spek, K. Lammertsma, Angew. Chem. 2004, 116, 3522 –
3524; Angew. Chem. Int. Ed. 2004, 43, 3440 – 3442.
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