Copper(I)-Catalyzed Asymmetric Conjugate Addition of 1,4-Dienes to β‑Substituted Alkenyl Azaarenes

Chiral azaarene compounds are extremely important due
to their
prevalence in pharmaceutical ingredients. Herein, an array of chiral
molecules bearing azaaryl groups is synthesized in moderate-to-excellent
yields with moderate-to-excellent Z/E ratios, high dr, and excellent enantioselectivity by a copper­(I)-catalyzed
asymmetric conjugate addition of 1,4-dienes to (E)-β-substituted alkenyl azaarenes. The reaction is carried
out under mild proton-transfer conditions, which enjoys very high
atom economy. Moreover, the reaction features a broad substrate scope
on (E)-α,β-unsaturated azaarenes as various
azaarenes are well tolerated, such as benzothiazole, thiazole, N-methyl-benzimidazole, benzoxazole, quinoline, isoquinoline,
pyrimidine, pyrazine, and triazine. Interestingly, the reaction with
(Z)-α,β-unsaturated azaarenes affords
the same products in excellent results but with a reversed absolute
configuration. DFT calculations indicate that the C–C bond-forming
nucleophilic addition is a Z-/E-
and enantio-selectivities-determining step and provides a rationale
for the origin of selectivities. At last, the synthetic utilities
of the product are showcased by several transformations, including
olefin metathesis, [4 + 2] cyclization, [2 + 1] cyclization, and cleavage
of the benzothiazole ring.