Diastereoselective pot-and atom-economical synthesis of densely-substituted polycyclic 1,2- and 1,2,3-fused indole scaffolds

摘要: Abstract A simple, efficient, one-pot sequential process for the preparation of a family 8,9-dihydropyrido[1,2–a]indol-6(7H)-one scaffolds in acceptable yields has been established under mild conditions. The Michael-hemiaminalization-oxidation reaction proceeds between methyl 2-(3-formyl-1H-indol-2-yl) acetate and trans-β-aryl/alkyl-substituted acroleins using pyrrolidine-BzOH as an efficient organocatalyst, followed by oxidation situ generated C,N-fused hemiaminal adducts presence PDC at room temperature. Excitingly, organobase-catalyzed highly diastereoselective (up to ≤9:1 dr) construction series pharmacologically attractive 1,2,3-fused tetracyclic indole with five contiguous chiral centers including all-carbon stereogenic center realized through our developed method. Moreover, PTSA combined catalytic systems promote uninterrupted Michael-cyclization reaction, N-alkylation carbazole produce interesting class 6-(9H-carbazol-9-yl)-6,7,8,9-tetrahydropyrido[1,2–a]indole derivatives manner.