Anomeric Amide Enabled Divergent Synthesis of Unsymmetrical Ureas, Carbamates, Thioesters, and Amides From Aldehydes.

Divergent synthetic transformations that convert a single precursor into a range of structurally distinct products are powerful tools for rapidly exploring chemical space. Although numerous strategies exist for converting versatile functional handles such as halides and boronic acids into a multitude of reactive intermediates, there remains a pressing need for methodologies that exploit alternative linchpin fragments to open complementary avenues to molecular complexity. Herein, we report a divergent, anomeric amide-enabled, aldehyde functionalization strategy, allowing access to unsymmetrical ureas, carbamates, thiocarbamates, thioesters, amines, or amides, all in a one-pot procedure. Unique to this transformation is the formation of N-Boc-hydroxamate intermediates, which serve as privileged platforms for orthogonal activation via Lossen-type rearrangements, single-electron transfer, or nucleophilic substitution, generating a diverse selection of reactive intermediates. Overall, this work establishes N-halo-O-activated hydroxycarbamate-type anomeric amides as valuable reagents for aldehyde diversification, offering a complementary approach to molecular complexity generation from feedstock compounds.