Isoflav-3-enes, substituted, synthesis

The estrogenic properties of isoflav-3-enes are well known and consequently, several derivatives of these chromene heterocycles have been the target of medicinal chemists. Varma and coworkers uncovered a useful enamine-mediated pathway to this class of compounds [142-144], Now the group has discovered a facile and general method for the MW-expedited synthesis of isoflav-3-enes substituted with basic moieties at the 2-position (Scheme 6.42) [145], These promising results are especially appealing in view of the convergent one-pot approach to 2-substituted isoflav-3-enes... 

Scheme 6.42 One-pot synthesis of 2-substituted isoflav-3-enes from in situ- generated enamines.

Scheme 14 Synthesis of 2-amino substituted isoflav-3-enes from enamines [69]...

The solvent-free MW-assisted synthesis of 2-amino-substituted isoflav-3-enes has been reported it ean be aehieved in one pot via the in situ generation of enamines and their subsequent reaetions with salicylaldehydes (Scheme 8.22). This environmentally friendly procedure does not require azeotropic removal of water using large excess of aromatic hydrocarbon solvents for the generation of enamines. 

Scheme 8.22 MW-assisted solvent-free synthesis of substituted isoflav-3-enes.

Bronstedt adds were used to catalyze the MW-accelerated multicomponent synthesis of substituted isoflav-3-enes 52 (Scheme 17.38) [96]. 

A one-pot synthesis of isoflav-3-enes 52 was achieved by the reaction of substituted salicylaldehydes 50 with enamines 51 in the presence of a catalytic amount of ammonium acetate under MWI for 2-6 min in 71-88% yields. The reaction of 50 with 51 in benzene under an inert atmosphere produced 52 in 45-55% yields (Scheme 10) (98JOC8038). 

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