Asymmetric [2,3]-wittig rearrangement induced by a chiral carbanion whose chirality was transferred from an epoxide

Article abstract of DOI:10.1021/ol052544h

(Chemical Equation Presented) The enantioselective [2,3]-Wittig rearrangement of 1-allyloxy-1-(naphthalen-2-yl)-4-siloxy-2,4-pentadienyl anion, derived from optically enriched 4,5-epoxy-1-(naphthalen-2-yl)-5-silyl-2-pentenyl allyl ether via a base-induced

Full text of DOI:10.1021/ol052544h

ORGANIC
LETTERS
2005
Vol. 7, No. 26
5913-5915
Asymmetric [2,3]-Wittig Rearrangement
Induced by a Chiral Carbanion Whose
Chirality Was Transferred from an
Epoxide
Michiko Sasaki,† Mariko Higashi,† Hyuma Masu,‡ Kentaro Yamaguchi,‡ and
Kei Takeda*,†
Department of Synthetic Organic Chemistry, Graduate School of Medical Sciences,
Hiroshima UniVersity, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan, and
Tokushima Bunri UniVersity, Shido, Sanuki, Kagawa, 769-2193 Japan
takedak@hiroshima-u.ac.jp
Received October 20, 2005
ABSTRACT
The enantioselective [2,3]-Wittig rearrangement of 1-allyloxy-1-(naphthalen-2-yl)-4-siloxy-2,4-pentadienyl anion, derived from optically enriched
4,5-epoxy-1-(naphthalen-2-yl)-5-silyl-2-pentenyl allyl ether via a base-induced ring opening of the epoxide followed by Brook rearrangement,
has been studied. The chirality of the epoxide was transferred to the alcohols in up to 97% ee, depending on the solvent used. The best result
was obtained in 1,4-dioxane at a temperature above room temperature.
[2,3]-Wittig rearrangement has become a powerful strategy
for organic synthesis, and its asymmetric variants have been
extensively explored in recent years.1 Among these, an
approach that employs a chiral nonracemic carbanion,2 which
is usually generated by enantioselective deprotonation with
a chiral base3 or a chiral ligand-bound metal reagent,4 appears
to be attractive in terms of simplicity and generality. We
report here asymmetric [2,3]-Wittig rearrangement triggered
by a nonracemic carbanion generated by chirality transfer
from epoxide via Brook rearrangement.5
In our earlier work6,7 on epoxysilane rearrangement (1 f
5), we showed that readily available epoxide chirality can
be transferred to a carbanion via Brook rearrangement (3 f
(4) (a) Kang, J.; Cho, W. O.; Cho, H. G.; Oh, H. J. Bull. Korean Chem.
Soc. 1994, 15, 732-739. (b) Manabe, S. J. Chem. Soc., Chem. Commun.
1997, 737-738. (c) Manabe, S. Chem. Pharm. Bull. 1998, 46, 335-336.
(d) Kawasaki, T.; Kimachi, T. Synlett 1998, 1429-1431. (e) Tomooka, K.;
Komine N.; Nakai, T. Tetrahedron Lett. 1998, 39, 5513-5516. (f) Kawasaki,
T.; Kimachi, T. Tetrahedron 1999, 55, 6847-6862. (g) Gibson, S. E.; Ham,
P.; Jefferson, G. R. J. Chem. Soc., Chem. Commun. 1998, 123-124. (h)
Tomooka, K.; Komine, N.; Nakai, T. Chirality 2000, 12, 505-509. (i)
Barrett I. M.; Breeden, S. W. Tetrahedron: Asymmetry 2004, 15, 3015-
3017.
(5) For reviews on Brook rearrangement, see: (a) Brook, M. A. Silicon
in Organic, Organometallic, and Polymer Chemistry, Wiley & Sons: New
York, 2000. (b) Brook, A. G.; Bassindale, A. R. In Rearrangements in
Ground and Excited States; de Mayo, P., Ed.; Academic Press: New York,
1980; pp 149-221. (c) Brook, A. G. Acc. Chem. Res. 1974, 7, 77-84. (d)
Moser, W. H. Tetrahedron 2001, 57, 2065-2084.
† Hiroshima University.
‡ Tokushima Bunri University.
(1) For reviews on [2,3]-Wittig rearrangement, see: (a) Nakai, T.;
Mikami, K. Chem. ReV. 1986, 86, 885-902. (b) Marshall, J. A. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 3, pp 975-1014. (c) Mikami, K.; Nakai,
T. Synthesis 1991, 594-604. (d) Nakai, T.; Mikami, K. Org. React. 1994,
46, 105-209. (e) Nakai, T.; Tomooka, K. Pure Appl. Chem. 1997, 696,
595-600.
(2) (a) Verner, E. J.; Cohen, T. J. Am. Chem. Soc. 1992, 114, 375-377.
(b) Hoffmann, R.; Bru¨ckner, R. Angew. Chem., Int. Ed. Engl. 1992, 31,
647-649. (c) Tomooka, K.; Igarashi, T.; Watanabe, M.; Nakai, T.
Tetrahedron Lett. 1992, 39, 5795-5798.
(3) (a) Marshall, J. A.; Lebreton, J. J. Am. Chem. Soc. 1988, 110, 2925-
2931. (b) Marshall, J. A.; Lebreton, J. J. Org. Chem. 1988, 53, 4108-
4112.
(6) (a) Takeda, K.; Kawanishi, E.; Sasaki, M.; Takahashi, Y.; Yamaguchi,
K. Org. Lett. 2002, 4, 1511-1514. (b) Sasaki, M.; Kawanishi, E.; Nakai,
Y.; Matsumoto, T.; Yamaguchi, K.; Takeda, K. J. Org. Chem. 2003, 68,
9330-9339.
10.1021/ol052544h CCC: $30.25
© 2005 American Chemical Society
Published on Web 11/18/2005

4) with a modest level of enantioselectivity and suggested
that acceleration of the reaction of the carbanion with an
electrophile (4 f 5) can suppress the racemization (Scheme
1).
rearrangement, for 5 min at -80° to -75 °C, the tandem
rearrangement products (E)- and (Z)-9 were obtained in 46%
yield and in racemic form (Table 1, entry 1). Although the
Table 1. [2,3]-Wittig Rearrangement of 8a
Scheme 1. Brook Rearrangement-Mediated Epoxysilane
Rearrangement
temperature yield recovered
ee
Z
(%)b
entry
solvent
THF
THF
THF
Et2O
Et2O
Et2O
(°C)
(%)
SMa (%)
E/Z
E
1
2
3
4
5
6
7
8
-80 to -75
-35 to -30
-25 to -30
-80 to -75
-35 to -30
-25 to -30
46
88
80
0
45
72
85
82
45
-
-
94
35
-
5.3:1
2.4:1
1.2:1
-
1:9.5 81 74
1:6.8 84 80
1:2.6 96 74
1:2.6 91 82
0
0
7
0
0
0
-
-
1,4-dioxane -25 to -30
1,4-dioxane -50 to -60
-
-
First, we examined tandem epoxysilane rearrangement/
[2,3]-Wittig rearrangement (1 (Y ) CH2CHdCHR) f 4 f
6), anticipating that the chirality of epoxide would be
transferred to the carbanion without racemization due to the
intramolecularity of the reaction with an electrophile, and
we focused on model compound 7, which was obtained from
the corresponding epoxyaldehyde.6 Treatment of a diaster-
eomeric mixture of 7 with a variety of bases resulted in
recovery of the starting material. Since the failure of the
reaction was attributed to insufficient acidity of the proton
at C-1 and a sterically congested environment around the
proton, we attempted to introduce a double bond between
the epoxysilane moiety and the aryl substituent. Among the
substrates examined, the 2-naphthyl derivatives 8a and 8b,
which were obtained from the corresponding epoxy alde-
hyde,8 provided the best results in terms of separability of
diastereomers (Figure 1).
a SM ) starting material. b Corrected for the ee of the starting material
(90% ee).
asymmetric induction remained poor in the solvent at higher
temperatures (entry 3), change in the solvent to other ethereal
solvents resulted in dramatic improvement in the asymmetric
induction (entries 5-8). The use of 1,4-dioxane9 provided
excellent enantiomeric purity (entries 7 and 8).
Reaction of diastereomer 8b proceeded in a similar manner
to give (R,E)- and (S,Z)-9, which are enantiomeric to those
obtained from 8a, respectively (Table 2). The absolute
configurations of 9 were assigned after conversion to 10,
respectively, by comparison of the chiral HPLC to the one
obtained from [2,3]-Wittig rearrangement of (S)-11.10
It is particularly noteworthy that chirality of a carbanion
derived from the epoxide, conjugated with both a naphthyl
group and a double bond, can be retained even above room
temperature. Although a full understanding of the actual
stereochemical process must await detailed mechanistic
studies, the observed stereospecificity suggests (1) the
formation of a carbanion precursor in a concerted manner
followed by [2,3]-Wittig rearrangement before racemization
or (2) the direct formation of [2,3]-Wittig rearrangement
products from a silicate derivative, a possible intermediate
in the Brook rearrangement, without involvement of a
carbanion intermediate.
Figure 1.
(8) For the preparation of 8a,b and determination of their absolute
stereochemistries, see the Supporting Information.
(9) To the best of our knowledge, the solvent has not been used in [2,3]-
Wittig rearrangement, probably because the rate of racemization of the
carbanion has been thought to be much faster than that of the reaction with
an electrophile at temperatures higher than its freezing point (11 °C).
(10) (S)-11 was prepared from the corresponding allyl alcohol according
to the kinetic resolution procedure of Sharpless (see ref 11). On the basis
of the results for [2,3]-Wittig rearrangement of (S)-12 (Table 3), we deduced
that [2,3]-Wittig rearrangement of (S)-11 proceeds with inversion of
configuration at the lithium-bearing carbon atom in the same way as reported
for the alkyl counterparts (see ref 2).
When optically enriched 8a was treated with n-BuLi (2.0
equiv) in THF, the most common solvent for [2,3]-Wittig
(7) Although the reaction of optically enriched 1 (Y ) SiMe2But, G )
CN) with benzyl bromide gave 5 in completely racemic form, the change
in Y to C(O)NiPr2 resulted in the formation of (Z)-5 in 21% yield and 37%
ee, which will be reported elsewhere. Kawanishi, E.; Takeda, K. Hiroshima
University, Japan. Unpublished results.
5914
Org. Lett., Vol. 7, No. 26, 2005

Table 2. [2,3]-Wittig Rearrangement of 8b
Table 3. [2,3]-Wittig Rearrangement of (S)-12
entry
solvent
THF
Et2O
Et2Oa
1,4-dioxane
1,4-dioxane
1,3-dioxane
additive
yield (%)
ee (%)c
1
2
3
4
5
6
-
-
-
-
95
75
39
70
50b
96
0
35
9
71
0
temperature yield recovered
ee
Z
(%)b
entry
solvent
THF
THF
THF
Et2O
Et2O
Et2O
(°C)
(%)
SMa (%)
E/Z
E
HMPA
-
1
2
3
4
5
6
7
8
-80 to -75
-35 to -30
-25 to -30
-80 to -75
-35 to -30
-25 to -30
54
91
90
0
51
71
92
81
36
-
-
84
41
-
E
E
15.4:1
-
12.0:1 90 36
2.6:1 91 58
8.1:1 97 45
5.3:1 96 49
0
0
5
-
-
0
0
a t-BuLi was used at -80 °C. b 40% of (S)-12 was recovered. c Corrected
-
-
for the ee of the starting material (99% ee).
1,4-dioxane -25 to -30
1,4-dioxane -50 to -60
-
-
to the decreased rate of racemization by chelation of the
lithium cation with the two oxygens. This is supported by
the fact that the addition of HMPA in 1,4-dioxane (entry 5)
and the use of 1,3-dioxane (entry 6) resulted in complete
racemization.
a SM ) starting material. b Corrected for the ee of the starting material
(91% ee).
In summary, we have demonstrated that chirality of
epoxide can be transferred to a carbanion via anion-induced
ring opening followed by Brook rearrangement and that the
carbanion can participate in [2,3]-Wittig rearrangement
without racemization. Moreover, we have shown that vinyl-
substituted benzyllithium derivatives, which have a marked
tendency to racemize, are relatively stable; clearly they are
sufficiently long-lived to be trapped by [2,3]-Wittig rear-
rangement without racemization in 1,4-dioxane at room
temperature. Detailed mechanistic interpretation of the ster-
eochemical results will be reported in a forthcoming full
article.
To obtain information about the configurational stability
of a carbanion between an aryl group and a double bond,
we decided to examine [2,3]-Wittig rearrangement of opti-
cally enriched (S)-12,11 in which racemization may be more
facile. Although no asymmetric induction was observed in
THF, reactions in 1,4-dioxane were found to show the best
enantioselectivity again to give (R)-13 (Table 3, entries 1
and 4).12 It is notable that less enantioselectivity was observed
at a lower temperature in Et2O (entries 2 and 3), suggesting
that the loss of chirality is at least partly attributed to the
racemization due to decreased rate of the [2,3]-Wittig
rearrangement at a lower temperature. These results are
consistent with the former possibility, although the latter
possibility of tandem epoxysilane rearrangement/[2,3]-Wittig
rearrangement cannot be ruled out.
Acknowledgment. This research was partially supported
by Grant-in-Aid for Scientific Research (B) 15390006, a
Grant-in-Aid for Scientific Research on Priority Areas
17035054 from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), and the Sasakawa Sci-
entific Research Grant from The Japan Science Society. We
thank the Research Center for Molecular Medicine, Faculty
of Medicine, Hiroshima University and N-BARD, Hiroshima
University for the use of their facilities.
The origin of the excellent enantioselectivity observed in
1,4-dioxane is unclear at present, but possibly it may be due
(11) (S)-12 was prepared from cinnamaldehyde by a three-step se-
quence: (1) PhLi, (2) kinetic resolution according to the protocol of
Sharpless, and (3) BrCH2CHdCH2. Gao, Y.; Klunder, J. M.; Hanson, R.
M.; Masamune, H.; Ko, S. Y.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
109, 5765-5780.
(12) The absolute configuration of the major enantiomer was determined
to be R by comparison of the chiral HPLC to the one derived from (R)-
mandelic acid (see Supporting Information), indicating an inversion of
configuration at the lithium-bearing carbon atom (according to the protocol
of Sharpless, see ref 11).
Supporting Information Available: Full experimental
details and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL052544H
Org. Lett., Vol. 7, No. 26, 2005
5915