A general diversified synthesis of carbazoles and the first synthesis of karapinchamine A

Abstract

[IPrAuCl]/AgSbF6 -catalyzed cyclization of the readily available 4-benzoxyl-1-(indol-2-yl)-2-alkynols occurred smoothly in 1,2-dichloroethane (DCE) in the presence of 4 Å MS to form a series of differently polysubstituted 2-oxygenated carbazole derivatives efficiently. Based on mechanistic study, a possible mechanism involving 1,3-migration of a benzoate group to form the allene, Au(+) -mediated cyclization-elimination to form a gold-carbene intermediate, and subsequent highly selective 1,2-migration has been proposed for the formation of carbazoles. Highly selective 1,2-migration referring to the two substituents R(3) and R(4) (R(4) =H, alkyl, and aryl group) was observed: (1) In the presence of both H and alkyl groups, 1,2-hydrogen migration is exclusive; (2) in the presence of a methyl group (R(3) ), propyl, isopropyl, 4-methylphenyl, and 4-chlorophenyl groups (R(4) ) migrate exclusively. Finally, the first total synthesis of the recently isolated naturally occurring carbazole alkaloid karapinchamine A in 5.2 g scale has been realized in 6 steps from commercially available chemicals without need for any protection-deprotection.

Keywords: carbazoles; carbenes; gold; migration; selectivity.