Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure

作者：Liu, Yang; Cheng, Li-Jie; Yue, Hai-Tao; Che, Wen; Xie, Jian-Hua^*; Zhou, Qi-Lin

来源：Chemical Science, 2016, 7(7): 4725-4729.

DOI：10.1039/c6sc00686h

• (-)-N-METHYLWELWITINDOLINONE C ISOTHIOCYANATE
• DYNAMIC KINETIC RESOLUTION
• CARBONYL-COMPOUNDS
• FORMAL SYNTHESIS
• RING-SYSTEMS
• INDOLES
• WELWITINDOLINONES
• FISCHERINDOLES

A divergent enantioselective approach to hapalindole-type alkaloids is described. The route features a ruthenium-catalyzed asymmetric hydrogenation of a ketone via DKR to construct the chiral trans-1-indolyl-2-isopropenylcyclohexane skeleton and a switchable sequence of methylation and acetylation/aldol reaction to access a chiral quaternary stereocenter. (+)-Hapalindole Q (1, 13 steps, 5.9% overall yield), (-)-12-epi-hapalindole Q isonitrile (2, 15 steps, 5.5% overall yield), (-)-hapalindole D (3, 14 steps, 2.3% overall yield), and (+)-12-epi-fischerindole U isothiocyanate (4, 14 steps, 3.0% overall yield) were synthesized in 13-15 steps from a commercially available material to demonstrate the application of this approach.

• 出版日期2016
• 单位南开大学