1308
Published on the web June 25, 2013
Doyle-Kirmse Reaction Using Triazoles Leading
to One-pot Multifunctionalization of Terminal Alkynes#
Tomoya Miura,* Takamasa Tanaka, Akira Yada, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510
(Received June 4, 2013; CL-130521; E-mail: tmiura@sbchem.kyoto-u.ac.jp, murakami@sbchem.kyoto-u.ac.jp)
1-Sulfonyl-1,2,3-triazoles undergo a Doyle-Kirmse reaction
and chloroform (4 mL) were put in a reaction vessel, and the
reaction mixture was simply stirred at room temperature (eq 1).
upon treatment with allylic sulfides in the presence of a
rhodium(II) catalyst to afford ¡-allyl-¡-sulfanylimines. Termi-
nal alkynes are regioselectively multifunctionalized by the
introduction of C-N, C-S, and C-C bonds through a one-pot
sequence consisting of a [3 + 2] dipolar cycloaddition reaction
with azide and subsequent Doyle-Kirmse reaction.
1a (0.40 mmol)
(0.40 mmol)
2a (0.44 mmol)
(40 µmol)
Ph
H
+
TsN3
+
SPh
(i) rt, 6 h
SPh
NTs
H
+
ð1Þ
CuTC
+
(ii) 120 °C/MW
Ph
30 min
[Rh2(OCOt-Bu)4] (10 µmol)
3aa 81%
(0.32 mmol)
+
CHCl3
(4 mL)
1-Sulfonyl-1,2,3-triazoles, readily available from terminal
alkynes,1 have recently attracted much interest as the precursor
of carbenoid species.2 Their ring-chain tautomerization forms
¡-diazoimines, which react with transition-metal complexes
to generate the corresponding ¡-imino metal carbenes. The
¡-imino group is of basic (nucleophilic) as well as electron-
withdrawing natures to confer a variety of unique reactivities on
the carbenoid species.3-5 For example, cycloaddition reactions
with nitriles,3a alkynes,3d,4 aldehydes,3k and isocyanates3m
furnish imidazoles, pyrroles, oxazolines, and imidazolones,
respectively. The electron-withdrawing nature renders the
carbenoids highly electrophilic to induce a semi-pinacol-type
rearrangement reaction3i,3j and addition of water,3f arylboronic
acids,3h and allylic alcohols.3l We then examined the possibility
of a Doyle-Kirmse reaction with the ¡-diazoimine intermedi-
ates, which might undergo [2,3]-sigmatropic rearrangement
upon treatment with allylic sulfides in the presence of
transition-metal catalysts, as with the case of ¡-diazo carbonyl
compounds.6 We now report a sequential one-pot transformation
of terminal alkynes, azides, and allylic sulfides into ¡-allyl-¡-
sulfanylimines. The transformation consists of a [3 + 2] dipolar
cycloaddition reaction and a Doyle-Kirmse reaction. Three
different bonds, i.e., C-N, C-S, and C-C, are introduced onto
the C-C triple bond with a regioselectivity, which makes a sharp
contrast to the one previously observed when allylic alcohols
were used (Figure 1).3l
Both 1a and tosyl azide were consumed after 6 h. The reaction
mixture was further stirred for 30 min at 120 °C under micro-
wave irradiation. After the reaction mixture was cooled at room
temperature, expeditious purification with silica gel chromatog-
raphy afforded 4-phenyl-4-phenylsulfanyl-5-(N-tosylimino)pent-
1-ene (3aa) in 81% yield based on 1a. Thus, terminal alkynes
were regioselectively multifunctionalized with the introduction
of C-N, C-S, and C-C bonds, during which molecular nitrogen
was the only waste product. It happened sometimes that the
imine product 3aa was partially hydrolyzed during chromato-
graphic purification, and therefore, 3aa was directly converted
to more stable compounds for isolation (eq 2). Addition of
LiAlH4 to the reaction mixture (0 °C, 30 min) gave the amine
4aa in 74% yield. On the other hand, addition of TsOH (60 °C,
18 h) promoted hydrolysis to give the aldehyde 5aa in 78%
yield.
LiAlH4
(1.3 equiv)
1a
+
SPh
NHTs
cat. [Cu]
cat. [Rh]
0 °C, 30 min
TsN3
1.0
equiv
+
2a
1.1
equiv
Ph
SPh
NTs
H
4aa 74%
ð2Þ
TsOH
(2.5 equiv)
Ph
SPh
O
3aa
60 °C, 18 h
Ph
5aa 78%
H
Phenylethyne (1a; 0.40 mmol), tosyl azide (TsN3; 1.0
equiv), allyl phenyl sulfide (2a; 1.1 equiv), CuTC (10 mol %;
TC: thiophene-2-carboxylate), [Rh2(OCOt-Bu)4] (2.5 mol %),
A plausible mechanism for the production of ¡-allyl-¡-
phenylsulfanylimine 3aa from phenylethyne (1a), tosyl azide,
and allyl phenyl sulfide (2a) is depicted in Scheme 1. Initially, a
[3 + 2] cycloaddition reaction of 1a with tosyl azide occurs at
room temperature in the presence of CuTC1b to give 4-phenyl-
1-tosyl-1,2,3-triazole (6a). A reversible ring-chain tautomeriza-
tion of 6a generates ¡-diazoimine 6a¤,7 which reacts with
rhodium(II) to afford ¡-imino rhodium carbene A with extrusion
of molecular nitrogen. Nucleophilic addition of 2a to the
electrophilic carbene center of A furnishes zwitterionic inter-
mediate B. The anionic rhodium releases an electron pair to
render the carbenoid carbon nucleophilic enough to induce [2,3]-
sigmatropic rearrangement. The product 3aa is formed with
release of rhodium(II).
–O
–N
O
H
N
OH
TsN3,
C
N2
+
Ts
R
C
C
H
C
R
cat. [Cu], cat. [Rh]
(ref. 3l)
–C
–N
–S
SPh
TsN3,
SPh
NTs
H
N2
+
R
C
C
H
C
C
cat. [Cu], cat. [Rh]
(this work)
R
–C
The sequential one-pot reaction followed by reduction with
LiAlH4 was carried out with various terminal alkynes, and the
Figure 1. One-pot multifunctionalization of terminal alkynes
through 1-sulfonyl-1,2,3-triazole intermediates.
Chem. Lett. 2013, 42, 1308-1310
© 2013 The Chemical Society of Japan
Miura, Tomoya
