Catalytic regioselective ?-Methylenation of ?,?-Unsaturated aldehydes using formaldehyde via vinylogous aldol condensation

Formaldehyde is used as a one-carbon electrophile(1) in several organic transformations to functionalize aldehydes,(2) ketones,(3) amines,(4) and alkenes.(1c,5) However, the reaction of formaldehyde with α,β-unsaturated aldehydes has rarely been studied.(6) In 1953, Pummerer and co-workers tested the reaction of formaldehyde with crotonaldehyde catalyzed by NaOAc and found the formation of a α-methylenated product that further self-reacted to produce a cycloadduct via Diels–Alder reaction (Scheme 1).(6a) After a decade, Farberov and co-workers carefully chose an α-methylated α,β-unsaturated aldehyde (to avoid α-functionalization) for the Mannich reaction with diethylammonium chloride and formaldehyde to obtain a γ-aminomethylated product that underwent thermal elimination at high temperature and high vacuum to give a γ-methylenated product.(6b) Though the unsaturated carbonyl compounds such as ketones, esters, and lactones have been extensively studied for the vinylogous aldol reaction involving silyl ethers(7a−c) and dienamine(7d) intermediates, α,β-unsaturated aldehydes have rarely been explored.(8) To the best of our knowledge, there is no report in the literature for the vinylogous aldol reaction (or condensation) of formaldehyde with α,β-unsaturated aldehydes.by Mahesh S. Kutwal, Sachin Dev, and Chandrakumar Appaye