Metal-free deformylation strategy enables sustainable Hantzsch-type pyridine synthesis in neat water
Xiao-Yu Yang1, Xue Li1, Jia Xu1
1College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing, 402160, China.
Abstract:
A deformylation-driven multicomponent reaction to access Hantzsch-type pyridine was first realized via a domino Michael/retro-Michael/Aldol/deformylation cascade. This operationally simple protocol fulfills green chemistry principles by employing readily available feedstocks in neat water under metal-free conditions. Mechanistic investigations establish deformylation of 3-formylchromones is the pivotal activation step, enabling the domino pathway toward pyridines while circumventing energy-intensive decarboxylation. Unprecedented in scope, the strategy accommodates diverse electrophiles and functionalized chromones, achieving 58-85% yields. This rationally designed deformylation cascade provides a sustainable blueprint for synthesizing medicinally important heterocycles without transition-metal contamination.
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