Further Studies on the Direct Synthesis of α, β-Unsaturated Ketimines and α, β-Enones by Chemoselective Dehydrative Addition of Functionalized Alkenes to Secondary Amides

Described in this paper are the results of an investigation on the extension of the C-H alkyliminylation and acylation of alkenes with secondary amides. The nucleophilic partner has been extended to cover a series of functionalized alkenes bearing functional groups including ester, alpha, beta-unsaturated ester, uncongested ketone groups, as well as enol derivatives of acetaldehyde such as enol ether and enamides. The electrophilic partner has been extended from N-(2,6-dimethylphenyl) and N-methyl amides to N-n-butyl, and N-cyclohexyl amides. The results demonstrated that the method can be used to synthesize a number of functionalized alpha, beta-unsaturated ketimines and alpha, beta-enones in an efficient, high yielding, and one-pot manner. The method was applied to a concise synthesis of (E)-6-styryltetrahydro-2H-pyran-2-one (5), an immediate intermediate in the syntheses of a series of styryllactone natural products including (+/-)-goniothalamine (6), (+/-)-goniothalamine oxide (7), (+/-)-goniodiol (8), (+/-)-leiocarpin A (9), (+/-)-9-deoxygoniopypyrone (10), and (+/-)-7-epi-goniodiol (11).