Simple Method for the Preparation of Esters from Grignard
Reagents and Alkyl 1-Imidazolecarboxylates
Thomas Werner and Anthony G. M. Barrett*
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, England
ReceiVed March 14, 2006
The reaction of Grignard reagents with alkyl imidazolecarboxylates, which were prepared from alcohols
with carbonyl diimidazole, gave the corresponding esters in good to excellent yields. This method
conveniently provides esters from alkyl halides and alcohols by C1-carbon chain extension.
Introduction
chloroformates to produce R-diazocarbonyl-â-ketoesters.5 How-
ever, there are few reports on the syntheses of esters from the
reaction of chloroformates with alkyl and aryl Grignard
reagents.6 Such condensation reactions invariably provide the
desired esters, only in low yields due to the concomitant
formation of tertiary alcohols derived from the triple addition
of the Grignard reagent.6c In these cases, yields of the esters
were improved by converting the chloroformates to the corre-
sponding acyl tributylphosphonium chlorides or pyrazole-1-
carboxylates.7 To the best of our knowledge, there is only one
report on the addition of phenylmagnesium bromide to methyl
1-imidazolecarboxylate, which gave methyl benzoate in 51%
yield.8 This observation encouraged us to develop a simple two-
step method for the preparation of esters from alcohols, Grignard
reagents, and carbonyl diimidazole (CDI).
Esters are invariably synthesized from the condensation
reaction of an alcohol with the corresponding carboxylic acid.
There are numerous methods for this transformation that are
known and well-established.1 During the course of our studies
toward the synthesis of a variety of resorcylate natural products,
we became interested in an alternative synthesis of esters from
the alkoxycarboxylation reaction of Grignard reagents that were
prepared from the corresponding alkyl halide.2 We considered
using alkyl chloroformates in this regard. However, such
transformations have two major drawbacks. First, the synthesis
of chloroformates from alcohols requires the handling of
phosgene or bis(trichloromethyl) carbonate.3 Additionally, chlo-
roformates are inconvenient to handle and are usually prepared
and directly allowed to react in situ.3c The reactions of
chloroformates with alkynylmetallic reagents have been widely
used to synthesize the corresponding 2,3-alkynyl esters.4 Ad-
ditionally, R-diazocarbonyl compounds have been metalated
using Grignard reagents and subsequently allowed to react with
Results and Discussion
A range of 1-imidazolecarboxylates 2, which were prepared
by the reactions of primary and secondary alcohols 1 with CDI9
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10.1021/jo060562m CCC: $33.50 © 2006 American Chemical Society
Published on Web 05/03/2006
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J. Org. Chem. 2006, 71, 4302-4304