Enantioselective Synthesis of Atropisomers Featuring Pentatomic Heteroaromatics by Pd-Catalyzed C–H Alkynylation

Abstract

Due to the lower rotational barriers, the catalytic asymmetric construction of atropisomeric species featuring a five-membered ring remains a formidable challenge. Herein, we describe a Pd-catalyzed atroposelective C–H alkynylation to synthesize such atropisomers. A wide range of atropisomers displaying either a stereogenic C–N or C–C bond featuring one or even two five-membered rings were obtained (up to 98% yield and up to >99% ee). Various five-membered heteroarenes, including pyrroles, thiophenes, benzothiophenes, and benzofurans were compatible with this protocol. Notably, this strategy offers the catalytic asymmetric synthesis of axially chiral 3,3′-bisbenzothiophene with good ee (93% ee). Computational studies revealed the key structural elements that differentiate the rotational barriers of benzothiophene and benzofuran moieties.