One‐Pot Morita–Baylis–Hillman/Allylic Substitution in Deep Eutectic Solvents: Access to γ‐Hydroxy Derivatives via Sequential CC and CX (X = P, N, S, B, Si) Bond Formation

A sustainable one-pot sequential CC/CX (X = P, N, S, B, Si) bond-forming strategy for synthesizing functionalized γ-hydroxy derivatives using ChCl/Gly (1:2) (ChCl = choline chloride and Gly = glycerol) deep eutectic solvent (DES) is reported. The methodology combines 1) an atom-economical Morita-Baylis-Hillman reaction for CC bond formation and 2) subsequent nucleophilic functionalization to afford diverse γ-hydroxy derivatives in good yields under mild, air/moisture-tolerant conditions. The DES system enables straightforward product isolation via water-induced precipitation, eliminating, in most of the cases, chromatographic purification. Notably, sulfinic acid reactivity displays striking stoichiometric control: 2 equiv. RSO₂H yields γ-hydroxy sulfones, while 1 equiv. selectively produces (E)-allylic sulfones (Z/E >1:99). Scalability is demonstrated through a fivefold multigram synthesis of γ-hydroxy amine 7aaa (96% yield), a pivotal intermediate for synthesizing antibacterial arylureas. The process exhibits outstanding green metrics (E-factor = 2.6), aligning with industrial benchmarks for bulk chemicals. This work establishes a practical, waste-minimized approach to privileged heteroatom-rich scaffolds, merging step economy with sustainable solvent technology.