Novel phenanthridinone analogues with an all-carbon quaternary stereocenter have been enantioselectively synthesized using the Birch–Heck sequence. Flat phenanthridinone structures have extensive bioactivity but consequently also suffer from poor therapeutic selectivity. The addition of a quaternary center to the phenanthridinone skeleton has the potential to generate more complex analogues with improved selectivity. Unfortunately, no general synthetic pathway to such derivatives exists. Herein we report a four-step process that transforms inexpensive benzoic acid into 22 different quaternary carbon-containing phenanthridinone analogues with a variety of substituents on all three rings: alkyl groups at the quaternary center; methyl, methoxymethyl, or para-methoxybenzyl on the amide nitrogen; and halogen and methyl substituents on the aryl ring. Good to very good enantioselectivity was demonstrated in the key intramolecular desymmetrizing Mizoroki–Heck reaction. Transformations of the Heck reaction products into molecules with potentially greater therapeutic relevance were also accomplished.

A nontraditional approach to synthesizing aryl vinyl sulfides is described. 2,2-Diphenyl-1,3-oxathiolane slowly liberates a vinyl sulfide anion under basic conditions. Using a Pd/Xantphos catalyst system to activate a wide range of aryl bromides, this transient sulfide species can be effectively trapped and fed into a traditional Pd/Pd catalytic cycle. Scope and limitations of the methodology are presented along with significant discussion of a competitive C-S bond activation by this catalyst system.

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