Angewandte
Chemie
Synthetic Methods
A Reaction of Triazoles with Thioesters to Produce b-Sulfanyl
Enamides by Insertion of an Enamine Moiety into the Sulfur–Carbonyl
Bond**
Tomoya Miura,* Yoshikazu Fujimoto, Yuuta Funakoshi, and Masahiro Murakami*
Abstract: N-Sulfonyl-1,2,3-triazoles react with thioesters in the
presence of a rhodium(II) catalyst to produce b-sulfanyl
enamides in a stereoselective manner. The reaction proceeds
through generation of an a-imino rhodium carbene complex,
nucleophilic addition of the sulfur atom of a thioester onto the
carbenoid carbon atom, and subsequent intramolecular migra-
tion of the acyl group from the sulfur atom to the imino
nitrogen atom. The method is successfully applied to a ring-
expansion reaction of thiolactones, thus leading to the for-
Figure 1. Commercially available drugs with a sulfur-containing
medium-ring lactam.
mation of sulfur-containing lactams.
N
-Sulfonyl-1,2,3-triazoles are readily prepared by a copper-
[
14]
(
I)-catalyzed cycloaddition reaction of terminal alkynes with
carbene complexes. We now report that, when thioesters
[1]
sulfonyl azides. Their ring–chain tautomerization generates
a-imino diazo compounds, although the equilibrium lies far
towards the triazole form, in general. Transition-metal
catalysts, especially rhodium(II) carboxylate dimers, can
efficiently trap the transient a-imino diazo compounds in
the form of an a-imino carbene complex, which exhibits
a variety of unique reactivities depending on the substrates.
In the reactions with unsaturated compounds such as
alkynes, allenes, nitriles,
cyanates and isothiocyanates, and indoles, they serve as
are subjected to the rhodium(II)-catalyzed reaction with N-
sulfonyl-1,2,3-triazoles, the sulfur–carbonyl bond is cleaved
and an enamine moiety is inserted to give b-sulfanyl enamides
with a Z configuration.
Initially, 4-phenyl-1-tosyl-1,2,3-triazole (1a) was prepared
from phenylacetylene and tosyl azide according to the
[15]
[
2]
[16,17]
[3]
procedure
using
copper(I)
thiophene-2-carboxylate
[1c]
(CuTC). The triazole 1a (0.20 mmol) was mixed with S-
phenyl thioacetate (2a, 0.30 mmol), [(tBuCO ) Rh ]
[
4]
[5]
[3a]
[6]
aldehydes and imines, iso-
2
4
2
[
7]
[8]
(2.0 mol%), and 4 molecular sieves (M.S.) in chloroform
(2 mL), and the mixture was heated at 708C for 1 hour
(Scheme 1). After chromatographic isolation from silica gel,
N-(2-phenyl-2-(phenylthio)vinyl)-N-tosylacetamide (3a) was
obtained in 96% yield as a single stereoisomer within the
the 1,3-dipoles to afford the corresponding [3+2] cyclo-
adducts. When reacted with alcohols and amides, they
[9]
[10]
offer an enamine moiety which inserts into the OÀH and NÀH
bonds, respectively. As a continuation of our studies on the
application of N-sulfonyl-1,2,3-triazoles as carbene precur-
sors, we became interested in the reactions with organosulfur
1
[18]
detection limits of H NMR spectroscopy. The configura-
tion of the double bond of 3a was confirmed as Z by NOE
studies. In a formal sense, an enamine moiety was stereose-
lectively inserted into the sulfur–carbonyl bond of 2a. We
assume that the reaction is initiated by a ring–chain tautome-
rization of 1a to generate the a-diazo imine 1a’, which reacts
with a rhodium(II) catalyst to afford the a-imino carbene
[11]
compounds because of the importance of sulfur-containing
compounds in the field of pharmaceuticals (Figure 1).
[12]
We have recently shown that the reaction with thionoest-
ers [RC(S)OR’] leads to the formation of 4-thiazolines, which
are further converted into 2,5-disubstituted thiazoles by
deprotective aromatization. In contrast, there is no report
which describes the reaction of thioesters [RC(O)SR’] with
rhodium(II)-stabilized carbene complexes, including a-imino
[13]
[
*] Dr. T. Miura, Y. Fujimoto, Y. Funakoshi, Prof. Dr. M. Murakami
Department of Synthetic Chemistry and Biological Chemistry, Kyoto
University
Katsura, Kyoto 615-8510 (Japan)
E-mail: tmiura@sbchem.kyoto-u.ac.jp
[
**] This work was supported in part by Grants-in-Aid for Scientific
Research (S) and (B) from MEXTand the ACT-C program of the JST.
Y. Funakoshi thanks the JSPS for Young Scientists for a Research
Fellowship.
Scheme 1. Rhodium(II)-catalyzed reaction of the triazole 1a with the
thioester 2a. Ts=4-toluenesulfonyl.
Angew. Chem. Int. Ed. 2015, 54, 9967 –9970
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9967