Homoaldol and aldol reactions from common enolates and oxirance: Reaction of reductively generated chromium enolates through cationic rearrangement

Article abstract of DOI:10.1246/cl.2002.142

Enolates generated from α-bromo esters by the reduction with Bu₆CrLi₃ react with oxiranes to afford γ-hydroxy esters and β-hydroxy esters, depending on the Lewis acid used as a promoter.

Full text of DOI:10.1246/cl.2002.142

142
Chemistry Letters 2002
Homoaldol and Aldol Reactions from Common Enolates and Oxiranes:
Reaction of Reductively Generated Chromium Enolates through Cationic Rearrangement
Makoto Hojo, Kyosuke Sakata, Xiamuxikamaer Maimaiti,y Junya Ueno, Hisashi Nishikori, and Akira HosomiÃ
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba Ibaraki 305-8571
(Received November 8, 2001; CL-011122)
Table 1. Reaction of bromo ester 1 with oxiranes in the presence
of Et3Ala
Enolates generated from ꢀ-bromo esters by the reduction
with ‘‘Bu6CrLi3’’ react with oxiranes to afford ꢁ-hydroxy esters
and ꢂ-hydroxy esters, depending on the Lewis acid used as a
promoter.
Enolates are a fundamental species for organic synthesis, and
the aldol reaction is a representative reaction of enolates, where
both the carbon-carbon bond formation and the creation of a
functional hydroxy group for the further synthetic manipulations
are achieved in a single event.1 As for the homologue, homoaldol
reaction, synthetic equivalents of homoenolates are usually used
as nucleophiles toward carbonyl compounds.2
We recently found that ꢀ-halo carbonyl compounds reacted
with an equimolar amount of ‘‘Bu6CrLi3’’3 to generate enolates
under mild conditions.4 These enolates reacted chemoselectively
with the electrophiles added afterward, in contrast to reactions
with Cr(II) reagents as reductants, where only by the Barbier-type
procedure, enolates reacted with electrophiles. This stepwise and
so-called Grignard-type procedure revealed an interesting feature
in the reactivity of the enolates.
We report herein two reactions, homoaldol and aldol
reactions of the common enolates and oxiranes, depending on
the Lewis acid used as a promoter (eqs 1 and 2).
(entries 4 and 5). In the reaction of 1a with styrene oxide,
regioisomeric homoaldol product 2h (69%) and ꢂ-hydroxy ester
3d (23%) were obtained (eq 3).
The enolate reductively generated from ethyl ꢀ-bromoiso-
butyrate (1a) with ‘‘Bu6CrLi3’’ did not react with propylene
oxide. When a solution of propylene oxide-Et3Al in THF
prepared in advance at À78 ꢀC was transferred to the solution
of the enolate at À78 ꢀC, and the temperature of the resultant
mixture was raised to room temperature, a mixture of ꢁ-hydroxy
ester 2a and its cyclized ꢁ-lactone 2a0 was obtained in 76%
combined yield. The results of the straightforward homoaldol
reaction are summarized in Table 1.
Both enolates derived from 1a and 1b reacted with some
types of oxiranes to afford homoaldol products in good yields.
Functionalized oxiranes bearing a chlorine atom and a phenoxy
group also provided the corresponding homoaldol products
We were interested in the formation of ꢂ-hydroxy ester 3d in
eq 3, and found that on using EtAlCl2 as the Lewis acid, the course
of the reaction dramatically changed, and only ꢂ-hydroxy ester 3
was obtained. These results are shown in Table 2.
The rearrangement of oxiranes to aldehydes catalyzed by a
Lewis acid was previously reported.5 Although this sort of
rearrangement is possibly involved in the present reaction, it is
worthy of note that the cationic rearrangement took place in the
presence of a nucleophilic enolate, and the enolate reacted only
with the rearranged aldehyde selectively.6 In the reaction with
styrene oxide, the produced aldol 3d is identical with the product
from a reaction of the enolate with highly enolizable phenylace-
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
143
Table 2. Reaction of bromo ester 1 with oxiranes in the presence
of EtAlCl2
a
This work was partly supported by Grants-in-Aid for
Scientific Research from the Japan Society for the Promotion of
Science (JSPS), Grants-in-Aid for Scientific Research on Priority
Areas from the Ministry of Education, Culture, Sports, Science
and Technology, Japan, and CREST, Science and Technology
Corporation (JST). X. M. acknowledges support from Xinjiang
Institute of Chemistry, Chinese Academy of Sciences.
Dedicated to Prof. Teruaki Mukaiyama on the occasion of his
75th birthday.
References and Notes
A visiting researcher from Xinjiang Institute of Chemistry,
Chinese Academy of Sciences.
y
1
T. Mukaiyama, in ‘‘Organic Reactions,’’ ed. by W. G.
Dauben, John Wiley & Sons, New York (1982), Vol. 28,
Chap. 3, p 203.
toaldehyde (entry 4). Unfortunately, epichlorohydrin and glyci-
dyl phenyl ether did not provide the desired aldol products, while
from 1,1- and 1,2-disubstituted oxiranes, aldol products were
obtained in high yields (eqs 4 and 5); the latter reaction
corresponds to the reaction between the enolate derived from
ethyl isobutyrate and methyl benzyl ketone.
2
3
D. Hoppe, Angew. Chem., Int. Ed. Engl. 23, 932 (1984).
A tentatively used formula ‘‘Bu6CrLi3’’ expresses only the
molar ratio of butyllithium employed to chromium(III) salt,
since the structure of the species is not clear at present.
M. Hojo, K. Sakata, N. Ushioda, T. Watanabe, H. Nishikori,
and A. Hosomi, Organometallics, 20, 5014 (2001).
B. Rickborn, in ‘‘Comprehensive Organic Synthesis,’’ ed. by
B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol. 3,
Chap. 3, p 733; K. Maruoka, T. Ooi, S. Nagahara, and H.
Yamamoto, Tetrahedron, 47, 6983 (1991); K. Maruoka, N.
Murase, R. Bureau, T. Ooi, and H. Yamamoto, Tetrahedron,
50, 3663 (1994).
4
5
6
7
Products derived from the rearrangements of other groups,
such as alkyls and halogen of the Lewis acid used were not
detected.
When BF3ÁOEt2 and ZnCl2 were used in the reaction of 1a
with ethyloxirane (corresponds to eq 6), yields of aldol 3b
were 67% and 28%, respectively. In the reaction of 1a with
octyloxirane using ZnBr2, 74% yield of homoaldol products
2c þ 2c0 were obtained.
Reactions with other Lewis acids were briefly examined, and
we found that SnCl4 also promoted the reactions giving ꢂ-
hydroxy esters 3 (eqs 6–8).7 Further synthetic application is now
under investigation.