ORGANIC
LETTERS
2008
Vol. 10, No. 22
5223-5225
GaCl3- and TiCl4-Catalyzed Insertion of
Isocyanides into a C-S Bond of
Dithioacetals
Mamoru Tobisu,† Sana Ito, Aki Kitajima, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity,
Suita, Osaka 565-0871, Japan, and Frontier Research Base for Global Young
Researchers, Graduate School of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan
Received September 23, 2008
ABSTRACT
The insertion reaction of isocyanide into a C-S bond of dithioacetals is catalyzed by GaCl3 or TiCl4 to afford thioimidates containing an
r-alkylthio group. Balanced thiophilicity of these Lewis acids is critical for efficient catalysis.
Dithioacetals, especially 1,3-dithianes, are recognized as
versatile intermediates in organic synthesis.1 The use of the
lithiated dithioacetal as a masked nucleophilic acylating agent
is particularly valuable, and for this purpose, the dithioacetal
functionality is ultimately converted into a sulfur-free car-
bonyl compound.2 Dithioacetals also serve as synthetic
precursors for several organosulfur compounds in substitution
reactions, in which one of the two sulfur groups is displaced
by a nucleophile, such as organolithium and -magnesium
reagents.1b,c In contrast, insertion reactions into the C-S
bond of dithioacetals, which afford products bearing two
sulfur-based functionalities, have not been thoroughly in-
vestigated, and successful examples are limited to intramo-
lecular processes.3,4 Herein, we report the intermolecular
insertion of isocyanides into the C-S bond of dithioacetals
catalyzed by GaCl3 and TiCl4 (eq 1).
As part of our research program, which is directed at the
development of new reactions using isocyanides as a C1
component,5 we recently reported the Brønsted and Lewis
acid catalyzed insertion of isocyanides into the C-O bond
† Frontier Research Base for Global Young Researchers.
(1) Selected reviews: (a) Bulman Page, P. C.; van Niel, M. B.; Prodger,
J. C. Tetrahedron 1989, 45, 7643. (b) Luh, T.-Y. Acc. Chem. Res. 1991,
24, 257–263. (c) Luh, T.-Y.; Lee, C.-F. Eur. J. Org. Chem. 2005, 3875.
(d) Takeda, T. Bull. Chem. Soc. Jpn. 2005, 78, 195.
(4) Intermolecular insertion of CO into the C-S bond of N,S-acetals
has been reported: Khumtaveeporn, K.; Alper, H. J. Org. Chem. 1994, 59,
1414
.
(2) Gro¨bel, B.-T.; Seebach, D. Synthesis 1977, 357.
(5) (a) Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.; Murai, S. J. Am.
Chem. Soc. 2003, 125, 7812. (b) Oshita, M.; Yamashita, K.; Tobisu, M.;
Chatani, N. J. Am. Chem. Soc. 2005, 127, 761. (c) Yoshioka, S.; Oshita,
M.; Tobisu, M.; Chatani, N. Org. Lett. 2005, 7, 3697. (d) Tobisu, M.; Oshita,
M.; Yoshioka, S.; Kitajima, A.; Chatani, N. Pure Appl. Chem. 2006, 78,
275. (e) Tobisu, M.; Kitajima, A.; Yoshioka, S.; Hyodo, I.; Oshita, M.;
Chatani, N. J. Am. Chem. Soc. 2007, 129, 11431. (f) Tobisu, M.; Yamaguchi,
S.; Chatani, N. Org. Lett. 2007, 9, 3351.
(3) (a) Nakamura, I.; Bajracharya, G. B.; Wu, H.; Oishi, K.; Mizushima,
Y.; Gridnev, I. D.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 15423. (b)
Peng, L.; Zhang, X.; Zhang, S.; Wang, J. J. Org. Chem. 2007, 72, 1192.
See also (c) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
2006, 45, 4473. (d) Nakamura, I.; Sato, T.; Terada, M.; Yamamoto, Y.
Org. Lett. 2007, 9, 4081. (e) Nakamura, I.; Sato, T.; Terada, M.; Yamamoto,
Y. Org. Lett. 2008, 10, 2649.
10.1021/ol802223a CCC: $40.75
Published on Web 10/25/2008
2008 American Chemical Society