Chen S, Pan J, Wang Y, Zhou Z * Nankai University, Tianjin, P. R. of China
Stereocontrolled Construction of the 3,4-Dihydrothiacarbazol-2(9
H)-one Skeleton by Using Bifunctional Squaramide-Catalyzed Cascade Reactions.
Eur. J. Org. Chem. 2014; 7940-7947
Key words
dihydrothia-carbazolones - Michael addition - thiolysis - squaramides
Significance
Reported is the enantioselective synthesis of 3,4-dihydrothiacarbazol-2(9H)-ones 3 by reaction of indoline-2-thiones 1 with N-alkenoylphthalimides 2 catalyzed by the chiral squaramide 4. Screening of organocatalysts with double hydrogen-bond donor ability led to squaramide
4 derived from l-tert-leucine as the best catalyst for this transformation affording high enantioselectivity.
The reaction conditions were optimized in terms of solvent, temperature, and catalyst
loadings. Lower temperatures (0 °C) culminated in lengthy reaction time and lower
yield but equivalent ee, while higher temperatures (40 °C) provided equivalent reaction
yields but loss of stereocontrol. The study of the reaction scope showed that the
presence of different substituents on both 1 and 2 were tolerated, but in some cases loss of stereocontrol without following a pattern
was observed.
Comment
The indole skeleton is an important class of heterocycles present in many natural
products with broad biological activities, and can be synthesized by many well-described
methodologies (see Review below). The thiopyran indole 3 was obtained by an activation process promoted by two hydrogen-bonding interactions
of 2 with the squaramide organocatalyst, followed by a Michael addition step and a thiolysis
reaction. The starting materials 1 and 2 are readily available. Although a mild process, the reported approach has long reaction
times and the study of the reaction scope is narrow.
Review
G. R. Humphrey, J. T. Kuethe Chem. Rev. 2006, 106, 2875–2911.
