Document Type

Article

Version

Author's Final Manuscript

Publication Title

The Journal of Organic Chemistry

Volume

87

Publication Date

2022

Abstract

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.

DOI

https://doi.org/10.1021/acs.joc.1c02523

Available for download on Sunday, January 01, 2023

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