Tetrahedron Letters
An efficient methodology to substituted furans via oxidation of functionalized
a-diazo-b-ketoacetates
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Phong Truong, Xinfang Xu, Michael P. Doyle
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 14 January 2011
DMDO oxidation of functionalized a-diazo-b-ketoacetates, formed by zinc triflate catalyzed Mukaiyama-
aldol condensation of methyl diazoacetoacetate with aldehydes, occurred in quantitative yield to form
dihydrofuranols that undergo acid catalyzed dehydration under mild conditions to generate 3-methoxy-
furan-2-carboxylates in good yield.
Dedicated to Harry Wasserman on the
occasion of his 90th birthday
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Diazoacetate
Vicinal-tricarbonyl
Dimethyldioxirane
Oxidation
Furan
1. Introduction
The advantages of this procedure are the ease of preparation and
handling of the diazoacetoacetate reactants, the quantitative oxida-
The vicinal tricarbonyl (VTC) moiety is an important functional
unit in organic synthesis. This is mainly due to the highly electro-
philicnatureof thecentralcarbonylcarbon, whichcanundergobond
formation with a variety of nucleophiles.1 The first VTC compound
was synthesized in 1890,2 and since then there have been a large
number of methods developed for their preparation.3 In what have
been an insightful contributions to the synthetic developments that
utilize this chemistry, Wasserman and coworkers demonstrated
multiple applications of the VTC system in the synthesis of b-lac-
tams,4 alkaloids,5 pyrroles,6 and indolizidines.7
In one application Wasserman used VTC compounds in a novel
synthetic route directed to the synthesis of substituted furans
(Scheme 1, Eq. 1),8 an important class of compounds due to their
abundance in natural products and biologically relevant molecules.
In this methodology, the VTC unit was prepared by oxidation of
phosphorus ylides that were synthesized from enolates of acyl phos-
phoranylidine carboxylates. Subsequent dehydration using PTSA
yielded 3-hydroxy-furan-2-carboxylates in moderate yields. Herein,
we report an improved approach for the synthesis of substituted
tion under neutral conditions, and the conversion of the VTC com-
pounds to alkoxy-furans under mild conditions.
2. Results and discussion
Our synthesis begins with commercially available aldehydes A
and methyl
transfer to methyl acetoacetate.10
clude B are stable under a wide range of conditions.11 TBSO-
functionalized -diazo-b-ketodicarbonyl compounds were
obtained by a convenient one-pot Mukaiyama-aldol reaction of
a-diazoacetoacetate B that is easily prepared by diazo
a
-Diazoacetoacetates that in-
a
1
aldehydes A and methyl
a-diazoacetoacetate B in high yield
(Scheme 2).9 The TBSO-functionalized condensation products (1)
were easily hydrolyzed with 4 N HCl in THF to form the
corresponding alcohol products 2 in high yields (Table 1).
With a variety of functionalized
a-diazo-b-ketodicarbonyl 2 in
hand, we next sought to oxidize the diazo group to a carbonyl
group. We initially began with t-butyl hypochlorite as an oxidant,
since several reports have shown that t-butyl hypochlorite
furans that utilize the oxidation of functionalized
a-diazo-b-
can generate VTC compounds from
a-diazo-b-dicarbonyl com-
pounds.12 In our hands, however, the use of t-butyl hypochlorite
acetoacetates, formed by zinc triflate catalyzed Mukaiyama-aldol
condensation of alkyl diazoacetoacetates with aldehydes,9 to gener-
ate VTC systems using dimethyldioxirane (DMDO) (Scheme 1, Eq. 2).
afforded the desired product in moderate yield along with other
unidentified by-products. As Saba reported that
a-diazo-b-
dicarbonyl compounds were oxidized to VTC derivatives using
dimethyldioxirane (DMDO) in high yield,13 we subjected diazo
substrates 2 to DMDO.14 This process resulted in the quantitative
oxidation of the full range of diazo compounds 2. The oxidized
⇑
Corresponding author. Tel.: +1 11 301 405 1788; fax: +1 11 301 314 2779.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.