Photocatalyzed Selective α‑Monoalkylation\nof Aqueous Acetaldehyde for Synthesis of α,β-Unsubstituted\n1,4-Ketoaldehydes

The\ndirect utilization of aqueous acetaldehyde as an industrially\nimportant aqueous chemical has been hampered in organic synthesis\ndue to the high reactivity of acetaldehyde. Herein, the first metal-free\nphotocatalyzed selective α-monoalkylation of commercially available\nand safe to handle aqueous acetaldehyde (40 wt %) with inexpensive\nα-chloro/bromoacetophenones has been developed using 0.5 mol\n% 4CzIPN as an organic photosensitizer, which provides easy access\nto high-added-value α,β-unsubstituted 1,4-ketoaldehydes.\nThe reaction features a broad substrate scope, high functional group\ntolerance, gram-scalability, operational simplicity, and mild reaction\nconditions. Moreover, the synthetic applications are demonstrated\nby directly using aqueous solutions of acetaldehyde as synthetically\nuseful a C2 synthon for the modular and expeditious synthesis of various\nbiologically active γ-aminoketones through the reductive amination\nof the α,β-unsubstituted 1,4-ketoaldehyde products with\ncyclic secondary amines, as well as the concise gram-scale total synthesis\nof pentabromo- and pentachloropseudilins.