C O M M U N I C A T I O N S
Table 1. Esterification of Carboxylic Acids with Diazoalkanes
Generated in Situ by the Oxidation of
carboxylic acid substrate. In that experiment, the diazo intermediate
was transformed into benzaldehyde azine, which was also the
primary byproduct in the presence of substrate (∼20% yield). This
competing reaction (diazo compound w azine)13 is believed to form
the basis for the requirement that excess diazo precursor be used
to achieve high yields in the esterifications. The important conclu-
sion from the spectroscopic studies is that the diazo intermediate
is consumed as it is formed and thus poses little or no safety hazard.
In summary, we have developed a general method for the
esterification of carboxylic acids with diazoalkanes prepared in situ
by the oxidation of TBSH derivatives with (difluoroiodo)benzene.
The procedure appears to be widely applicable with regard to both
diazo precursors and carboxylic acid substrates. Although there are
many options for ester bond formation in synthesis, the reaction of
carboxylic acids with diazo intermediates holds a special place in
fine chemical synthesis. The example of the transformation of
gibberellic acid to form the photochemically labile nitroveratryl
ester (entry 9, Table 1) perhaps best illustrates the type of
application where the present methodology may be useful.
N-tert-Butyldimethylsilylhydrazones (TBSHs) with
(Difluoroiodo)benzenea
Acknowledgment. Financial support from the National Science
Foundation (CHE-0312298) is gratefully acknowledged. M.E.F. also
acknowledges the NSF for a predoctoral graduate fellowship.
Supporting Information Available: Detailed experimental pro-
cedures and complete spectroscopic data for all new compounds (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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a Standard conditions for TBSH formation: 1 equiv of carbonyl-
containing substrate, 1.05 equiv of 1,2-bis(tert-butyldimethylsilyl)hydrazine,
0.01 mol % Sc(OTf)3, neat, 0 f 23 °C (volatile byproducts, including
TBSOH, were removed in vacuo prior to esterification). Standard conditions
for esterification: 1.5 equiv of TBSH (0.1 M), 1 equiv of carboxylic acid
(∼0.07 M), 2.3 equiv of PhIF2 (∼0.15 M), 5 equiv of 2-chloropyridine
(∼0.3 M), CH2Cl2, -78 f 23 °C. b Yield after purification by column
chromatography on silica gel. c Esterification conducted with 3 equiv of
TBSH derivative. d Esterification run in 1:1 CH2Cl2/EtOAc. e Esterification
run in 9:1 CH2Cl2/EtOAc with 9 equiv of TBSH derivative. f Esterification
run in 99:1 CH2Cl2/Et3N with 18 equiv of TBSH derivative.
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