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

We report a sustainable one-pot sequential C-C/C-X (X = P, N, S, B, Si) bond-forming strategy for synthesizing functionalised γ-hydroxy derivatives using ChCl/Gly (1:2) (ChCl = choline chloride; Gly = glycerol) Deep Eutectic Solvent (DES). The methodology combines: i) an atom-economical Morita-Baylis-Hillman reaction for C-C bond formation; and ii) 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 was demonstrated through a 5-fold 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-minimised approach to privileged heteroatom-rich scaffolds, merging step economy with sustainable solvent technology.