Asymmetric Synthesis of an Atropisomeric β-Carboline via Regioselective Intermolecular Rh(I)-Catalyzed [2 + 2 + 2] Cyclotrimerization.

ABSTRACT: The rational design of atropisomeric small molecules is becoming increasingly common in chemical synthesis as a result of the unique advantages this property provides in drug discovery, asymmetric catalysis, and chiroptical activity. In this study, we designed a synthesis of a configurationally stable β-carboline in six steps. Our synthesis made use of an innovative Grignard addition/elimination reaction that formed an yne-ynamide precursor that then reacted with ethyl cyanoformate in a rhodium(I)-catalyzed [2+2+2] cyclotrimerization reaction to give the atropisomeric β-carboline in excellent yield, good enantioselectivity, and excellent regioselectivity. Extensive optimization of this transformation is described. Racemization kinetics experiments were also conducted on the individual atro

SUBMITTER: Hughes RR 

PROVIDER: S-EPMC11293437 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature