A Ruthenium-Catalyzed Cyclization to Dihydrobenzo[c]phenanthridinone from 7-Azabenzonorbornadienes with Aryl Amides

Abstract

An efficient ruthenium(II)-catalyzed tandem C−C/C−N bond formation with aryl amides and 7azabenzonorbornadienes has been developed to synthesize cis-fused dihydrobenzo[c]phenanthridinones. The amide group functions as a directing group as well as a leaving group and provides an easy access to the pharmaceutically useful benzo[c]phenanthridine alkaloids such as nitidine and fagaronine analogues. The present methodology is compatible with various functional groups with respect to azabicyclic alkenes and aromatic amides. The reaction mechanism involving directing-group-assisted C−H activation was proposed and supported by the deuterium labeling studies.

Cobalt(III)-catalyzed asymmetric ring-opening of 7-oxabenzonorbornadienes via indole C–H functionalization

“…mechanistic pictures of the CpCo-catalyzed ARO reactions where cisand trans-β-oxygen elimination work as the selectivity-determining step for enantioselective and racemic reactions, respectively. Such results are different from the previous cognition 47,[53][54][55][56][57][58][59][60][61][62][63][64] . As an extension, 7-azabenzonorbornadiene could also be applied in the similar ARO reactions in a diastereodivergent manner.…”

“…1b) [47][48][49] . Merging ARO reactions with transition-metal-catalyzed C-H activation has become an area of recent interest [50][51][52][53][54][55][56][57][58][59][60] . In this regard, the groups of Zheng and Li 53 , and Cramer 54 independently reported the ARO reactions of 7-azabenzonorbornadienes and other aza-bicyclic olefins under Rh-catalysis, in which β-nitrogen elimination was a key step.…”

“…However, to the best of our knowledge, the C-H activation-induced ARO reactions of 7-oxabenzonorbornadienes via β-oxygen elimination remained elusive, probably due to the competitive dehydration 61,62 or direct reductive elimination 63,64 as a side reaction pathway. Mechanistically, it was regarded that the ARO reactions proceeded via the exocoordination of a carbon-metal species to the olefin moiety, migratory insertion and cis-β-heteroatom elimination 47,[53][54][55][56][57][58][59][60] . And the migratory insertion was speculated as the enantioselectivity-determining step in the ARO reactions (Fig.…”

Ruthenium-catalyzed hydroarylation reactions as the strategy towards the synthesis of alkylated arenes and substituted alkenes

“…Jeganmohan et al 17 recently reported an intriguing method to synthesize pharmaceutically relevant dihydrobenzo[ c ]phenanthridinones through Ru-catalyzed hydroarylation of arylamides and 7-azabenzonorbornadienes. The amide group in the substrate can effectively act as both the leaving group and the directing group.…”

Lanthanide-catalyzed deamidative cyclization of secondary amides and ynones through tandem C–H and C–N activation

“…In the vast majority of C–H functionalizations, removing the amide directing group requires additional steps. 12 To date, there are only a few examples of catalytic cyclization using amide as a directing group and a leaving group, 13 and they are limited to tertiary aromatic amides. To our knowledge, cyclization reactions based on the merger of α-C–H and C–N activation of amides have not yet been realized.…”