Reductive deoxygenation using hydridozirconium enolates: A new synthesis of α,β-unsaturated esters

Article abstract of DOI:10.1016/S0040-4039(00)60795-5

An unusual new reaction of Cp₂ZrHCl transforms β-ketoesters into α,β-unsaturated esters in one step and provides a useful alternative to the traditional, three-step process of reduction, mesylation/tosylation, and elimination.

Full text of DOI:10.1016/S0040-4039(00)60795-5

Vol. 33. No. 49. PP.
in Great Britain
+
REDUCTIVE DEOXYGENATION USING
HYDRIDOZIRCONIUM ENOLATES:
A NEW SYNTHESIS OF a&UNSATURATED ESTERS
Alexander G. Godfrey and Bruce Ganem*
Department of Chemistry
Cornell University
Ithaca, New York
USA
An unusual new reaction of
provides a useful altemative to the
eliition.
transforms
three-step process
into
esters in one
and
The
hydrides to
has become a widely used alternative to
the initial products of have shown to
and stereoselective conjugate additions, cross-couplings and other strategic carbon-carbon
hydroboration and hydmalumination.
undergo highly
bond-forming
The most commonly used
which also reduces
reagent is
compounds3 and undergoes nucleophilic attack by
oxygen nucleophiles.4
we report that lithium enolates of
when treated with
are
transformed into a&unsaturated esters in a single step
1). The overall process amalgamates key
components of organozirconium hydride chemistry and enhances the utility of
which are already indispensable building blocks in organic synthesis.7
0
H
1
.
2
.
R
R’
7
461

7
4 6 2
The conversion of
the Table. Typically a THF or, preferably, dimethoxyethane @ME) solution of the
prepared using 1.2 of lithium is transferred into a vigorously stirred suspension of
commercially at with gradual warming to
After h, the
desired product is separated from insoluble organozirconium byproducts by the addition of hexanes (2-3
volumes), filtration and concentration. Conjugated unsaturated esters can be prepared from variously substituted
to cc&unsaturated esters by this method is rather general, as indicated in
lithium enolate
(
(Aldrich; 1.2
cyclic and acyclic
desired product
(Entries l-5). With
6) a similar reduction occurs, however the
addition under the reaction conditions.
also undergoes competing
Although the mechanism of
initial formation of enolate
heterogeneous reaction is unknown, the simplest possibility involves
1
2). Enolate 1 may undergo intermolecular hydroxirconation to produce
2
, probably as an aggregate, which would afford enoate 4 by p-elimination of 3. This proposal is consistent with
several lines of experimental evidence. (1) Besides being enolate
independently by reducing the enolate of ethyl cyclohexanonecarboxylate with
whereupon ethyl l-cyclohexenecarboxylate is formed in ca. 50% yield (2) The regiochemistry of
tion is likely directed by the electrophilic nature of the conjugated enolate, since control experiments
demonstrate that unconjugated enolates (e.g. the lithium enolate of cyclohexanone)
3) Beta-elimination of
1
=
not reduced by
(
bonds is commonly observed. and (4) numerous examples of stable
conium fragments like 3 have been
H
R
R
1
2
4
In conclusion, a new reaction involving reductive deoxygenation of
enolates has been
shown to transform
types. and can avoid the needless formation of
process of reduction. and elimination.
into
esters. The procedure accommodates a variety of structural
customarily observed in the traditional. three-step

7
463
TABLE: Reductive
via Conjugated
Product (Yield)’
Enolates
Entry
Reactant
0
1
0
2
3
(
70%)
0
0
(
67%)
4
Ph
6
(
a) Products were purified by flash column chromatography, and identified by
direct comparison with authentic samples. (b) Contaminated with ca. 10%
of

7
464
ACKNOWLEDGMENT: We thank the National Institutes of Health (GM 24054) for generous financial assis-
tance. Support of the Cornell NMR Facility by the NSF and NIH is gratefully acknowledged.
REFERENCES AND NOTES
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2
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.
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7
8
.
.
9
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and
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1
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1.
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1
1
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1964,156,
1
(Received in USA 9 July 1992; accepted 8 September 1992)