Journal of the American Chemical Society
Communication
Scheme 4. Proposed Reaction Pathways for the
Transformation
AUTHOR INFORMATION
Corresponding Authors
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Professor Takuya Kurahashi (Kyoto University) for X-
ray crystallographic analysis. We also appreciate Professor Hans-
■
Jurgen Federsel (AstraZeneca) for his kind advice to our
̈
manuscript. This work was supported financially by the Japanese
Ministry of Education, Culture, Sports, Science and Technology.
K.A. also acknowledges the Asahi Glass Foundation, Toyota
Physical and Chemical Research Institute, and Tokyo Institute of
Technology Foundation.
REFERENCES
■
(1) Bariwal, J. B.; Upadhyay, K. D.; Manvar, A. T.; Trivedi, J. C.; Singh,
J. S.; Jain, K. S.; Shah, A. K. Eur. J. Med. Chem. 2008, 43, 2279.
(2) (a) Ogawa, T.; Kumagai, N.; Shibasaki, M. Angew. Chem., Int. Ed.
2012, 51, 8551. (b) Fang, X.; Li, J.; Wang, C.-J. Org. Lett. 2013, 15, 3448.
(3) (a) Bappert, E.; Muller, P.; Fu, G. C. Chem. Commun. 2006, 2604.
̈
(b) Robinson, E. R. T.; Fallan, C.; Simal, C.; Slawin, A. M. Z.; Smith, A.
D. Chem. Sci. 2013, 4, 2193. (c) Vellalath, S.; Van, K. N.; Romo, D.
Angew. Chem., Int. Ed. 2013, 52, 13688. (d) Liu, G.; Shirley, M. E.; Van,
K. N.; McFarlin, R. L.; Romo, D. Nat. Chem. 2013, 5, 1049. (e) Abbasov,
M. E.; Hudson, B. M.; Tantillo, D. J.; Romo, D. J. Am. Chem. Soc. 2014,
136, 4492.
(4) Fukata, Y.; Okamura, T.; Asano, K.; Matsubara, S. Org. Lett. 2014,
16, 2184.
(5) For seminal works on isothiourea catalysts, see: (a) Birman, V. B.;
Jiang, H.; Li, X.; Guo, L.; Uffman, E. W. J. Am. Chem. Soc. 2006, 128,
6536. (b) Birman, V. B.; Li, X. Org. Lett. 2006, 8, 1351. (c) Kobayashi,
M.; Okamoto, S. Tetrahedron Lett. 2006, 47, 4347. For a review, see:
Taylor, J. E.; Bull, S. D.; Williams, J. M. J. Chem. Soc. Rev. 2012, 41, 2109.
(6) Results of further catalyst screening are described in the Supporting
Information.
(7) Although the corresponding acid chloride could be used as a
substrate, the enantioselectivity was slightly lower in a preliminary study
(91% yield, 88% ee, see the Supporting Information for details). In
addition, the generation of the anhydride in situ from the corresponding
carboxylic acid was also investigated, but the yield was much lower
despite the comparable enantioselectivity (19% yield, 97% ee, see the
Supporting Information for details). Further investigations for
optimization of these methods are currently ongoing.
(8) The presence of intramolecular nonbonded S···O interaction has
been recognized, see: (a) Minkin, V. I.; Minyaev, R. M. Chem. Rev. 2001,
101, 1247. (b) Nagao, Y.; Hirata, T.; Goto, S.; Sano, S.; Kakehi, A.;
Iizuka, K.; Shiro, M. J. Am. Chem. Soc. 1998, 120, 3104. (c) Brameld, K.
A.; Kuhn, B.; Reuter, D. C.; Stahl, M. J. Chem. Inf. Model. 2008, 48, 1. For
discussions on attractive no to σ*C−S interaction between the
acylammonium oxygen and the sulfur atom of isothiourea catalysts,
see refs 3b, d, e, and the following: (d) Birman, V. B.; Li, X.; Han, Z. Org.
Lett. 2007, 9, 37. (e) Leverett, C. A.; Purohit, V. C.; Romo, D. Angew.
Chem., Int. Ed. 2010, 49, 9479. (f) Liu, P.; Yang, X.; Birman, V. B.; Houk,
K. N. Org. Lett. 2012, 14, 3288.
(9) The presence of cation-π interaction between the acylammonium
cation generated by isothiourea catalysts and an aryl group in substrates
was suggested in literature on the basis of computational and
experimental studies, see ref 8f and the following: Belmessieri, D.;
Joannesse, C.; Woods, P. A.; MacGregor, C.; Jones, C.; Campbell, C. D.;
therefore seems to be mainly controlled by the defference of
cyclization rate between the intermediates II and VI and is also
reinforced by the face-selective sulfa-Michael addition, where the
selection system supported by the reversibility of sulfa-Michael
addition may impart the overall excellent enantioselectivity.10 In
addition, in the event where (E)-4 and (Z)-4 are generated
during the course of the reaction, they could be incorporated
back into the main catalytic process and ultimately lead to the
formation of the desired products in high enantioselectivities.
In summary, we have demonstrated the first net cycloaddition
approach to 1,5-benzothiazepines, realizing a facile synthetic
route to a number of benzothiazepine derivatives. The net
cycloaddition procedure resulted in excellent regioselectivity and
good stereoselectivity regardless of the steric and electronic
characteristics of the substrates. Mechanistic studies suggested
that the reversibility of the nucleophilic attack by sulfur-centered
nucleophiles to α,β-unsaturated acylammonium intermediates
imparts the high regio- and enantioselectivity of the trans-
formation. This method is potentially useful for the construction
of a library of optically active 1,5-benzothiazepines. Further
studies regarding both expansion of the substrate scope and
application of this methodology to the preparation of derivatives
for drug discovery are currently ongoing in our laboratory and
will be reported in due course.
ASSOCIATED CONTENT
■
Johnston, C. P.; Duguet, N.; Concellon
Org. Biomol. Chem. 2011, 9, 559.
́
, C.; Bragg, R. A.; Smith, A. D.
S
* Supporting Information
Experimental procedures including spectroscopic and analytical
data. This material is available free of charge via the Internet at
(10) Since the reaction rate was not affected by the concentration (see
the Supporting Information for details), the intramolecular cyclization
step is considered to be the rate-determining step.
D
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX