The chemistry of coumarin derivatives. Part 3. Synthesis of 3-alkyl-4-hydroxycoumarins by reductive fragmentation of 3,3′-alkyiidene-4,4′-dihydroxybis[coumarins]

Treatment of 3,3′-alkylidene-4,4′-dihydroxybiscoumarins] 1 with NaBH₃CN in refluxing MeOH affords 3-alkyl-4-hydroxycoumarins 2 and 4-hydroxycoumarin ( 3 ; Scheme 1). The reaction might take place via hydride trapping of alkylidenechromandiones C formed from 1 in a retro-Michael reaction. Such a retro-Michael reaction of 1 might be biologically relevant. The presence of C during the reductive fragmentation 1 → 2 is suggested by Diels-Alder and nucleophilic trapping of the alkylidenechromandiones C as well as from cross-over experiments with coumarins other than 3 (see Scheme 2). The reductive fragmentation of 1 allows the chemo- and regioselective synthesis of a variety of 3-alkyl-4-hydroxycoumarins 2 (see Table).