Copper(I)-Catalyzed Asymmetric Alkylation of α‑Sulfanyl Acetamides

α-Sulfanyl carbonyl moieties
are common structural
features
in bioactive molecules. Herein, a copper(I)-catalyzed enantioselective
alkylation of α-sulfanyl acetamides is disclosed, affording
a broad array of chiral α,α-disubstituted amides in high
yields with high enantioselectivity. Benzyl bromides, allyl bromides,
propargyl bromide, and non-activated alkyl iodides serve as suitable
alkylation electrophiles. Furthermore, structurally diversified amides
are well tolerated. Control experiments and NMR studies indicate that
α-phenylthioacetamide coordinates to the copper(I) catalyst
through chelation, leading to activation of the α-protons, facile
deprotonation, and subsequent formation of stabilized copper(I)-enolate.
Finally, various transformations based on the amide moiety, especially
the Weinreb amide, demonstrate synthetic utilities of the present
method, together with the formal synthesis of a presynaptic cholinergic
modulator (11).