Total synthesis of atropisomeric indolosesquiterpenoids N-N bond formation: dixiamycins A and B

N-N dimeric indolosesquiterpene alkaloids constitute a class of under-investigated architecturally intriguing natural products. Herein, we report the first chemical oxidation approach to the asymmetric total syntheses of these atropisomeric indolosesquiterpenoids through N-N bond formation. Specifically, dixiamycins A ( 1a ) and B ( 1b ) were prepared through a Cu( i )-mediated aerobic dehydrogenative dimerization from the naturally occurring monomer xiamycin A methyl ester ( 2b ); this preparation also represents the first total synthesis of dixiamycin A ( 1a ). The monomer xiamycin A methyl ester ( 2b ) was synthesized via a late-stage Buchwald Pd( ii )-mediated aerobic dehydrogenative C-N bond formation. The total synthesis of the naturally occurring N-N atropo-diastereomers dixiamycin A ( 1a ) and dixiamycin B ( 1b ) using a key Cu( i )-catalyzed aerobic oxidation of xiamycin A methyl ester ( 2b ) was developed.