Pd-Monothiosquaramides: Efficient Catalysts for the Enantioselective Imine Reduction of Dihydro-β-Carbolines

An efficient enantioselective synthesis of tetrahydro-β-carbolines (THBCs) using chiral metal-monothiosquaramides (M–MTSQs) was planned. The in situ generated Pd/Fe-monothiosquaramides (Pd/Fe-MTSQs) catalysed imine reduction of dihydro-β-carbolines exceptionally to afford chiral THBCs with an excellent enantiomeric excess (up to 98% ee). In a catalysis study, Pd-MTSQ 12 a (10 mol%) was found to be more efficient than Pd-MTSQ 12 b and Fe-MTSQs (13 a and 13 b) for enantioselective imine reduction of DHBCs 14 a–e. All the major chiral alkyl-THBC isomers 15 a–c (90% ee, 98% ee and 95% ee, respectively) were observed with R configuration which was explained by Si face hydride attack on alkyl DHBC imines (14 a–c). Surprisingly, S configuration was perceived for the major isomers of chiral aryl-THBCs 15 d and 15 e (95% ee and 96% ee, respectively) which was rationalized by Re face hydride attack on aryl DHBC imines (14 d and 14 e).