Stereocontrolled Construction of the 3,4‐Dihydrothiacarbazol‐2(9H)‐one Skeleton by Using Bifunctional Squaramide‐Catalyzed Cascade Reactions

Abstract

An efficient approach for the stereocontrolled construction of the 3,4‐dihydrothiacarbazol‐2(9H)‐one skeleton has been developed. In the presence of a bifunctional squaramide catalyst that was derived from L‐tert‐leucine, the asymmetric tandem Michael/thiolysis reactions of 9‐methylindoline‐2‐thiones and N‐alkynoylphthalimides proceeded efficiently to furnish the desired 3,4‐dihydrothiacarbazol‐2(9H)‐one derivatives in satisfactory yields with high levels of enantioselectivity (up to 98 % ee).

The Shape of the Archetypical Oxocarbon Squaric Acid and Its Water Clusters

“…In the field of asymmetric organocatalysis, Chen et al. designed novel bifunctional squaramide‐catalyzed cascade reactions . Moreover, Pedrosa et al.…”

N‐Heterocyclic Carbene‐Catalyzed [3+3] Annulation of Indoline‐2‐thiones with Bromoenals: Synthesis of Indolo[2,3‐b]dihydrothiopyranones

“…Heterocycles combining two separate biologically attractive frameworks are of great interest in synthetic chemistry and drug discovery . Therefore, the indolo[2,3‐ b ]dihydrothiopyranone system is of interest, and has been found to have potent analgesic activities, and is an inhibitor of rat brain AChE and human serum BuChE…”

Applications of Chiral Squaramides: From Asymmetric Organocatalysis to Biologically Active Compounds

“…The cascade Michael addition/thiolysis reactions of 9-methylindoline-2-thiones and N-alkenoylphthalimides were promoted by a chiral bifunctional squaramide catalyst C4 to give the desired products in acceptable yields with 54-98% ee (Scheme 4). [12] It is well known that C 3 -symmetrical compounds possess a number of advantages, e.g., they can reduce the number of possible diastereomers in catalytic intermediates and create a more sterically encumbered chiral space to reduce disadvantages, such as rotation and flexibility in enantiofacial control. Therefore, the C 3 -symmetry squaramides were designed by Dong et al by connecting the cichona alkaloids with the core of the squaric acid.…”

“…In 2014, Zhou reported an efficient process for the enantioselective synthesis of optically active 3,4‐dihydrothiacarbazol‐2(9 H )‐one derivatives, which are found in many bioactive naturally occurring compounds and pharmaceuticals. The cascade Michael addition/thiolysis reactions of 9‐methylindoline‐2‐thiones and N ‐alkenoylphthalimides were promoted by a chiral bifunctional squaramide catalyst C4 to give the desired products in acceptable yields with 54–98% ee (Scheme ) 12…”