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

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.