Copper-Mediated 3-N-Arylation of Flavins

Abstract

A generally applicable method for the direct 3-N-arylation of flavins using arylboronic acids and copper acetate was developed. The reaction conditions were optimized considering the lability of flavins in basic conditions and thermal heating. Donor- and acceptor-substituted arylboronic acids were used yielding 3-N-arylflavins in moderate to good yields by C(aryl)-N(imide) bond formation. UV and fluorescence measurements indicate an ortho­gonal orientation of the additional aromatic substituent to the flavin ring system. The arene substituent is not electronically coupled to the flavin π-system in the ground state, but electron-rich arene substituents in 3-N position significantly reduce the flavin emission intensity.

Key words

flavin - N-arylation - boronic acid - isoalloxazin - microwave - copper catalysis

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15

Substituents at 10-N have to be inserted in common synthetic protocols for flavin synthesis like the well-known Kuhn synthesis. These routes suffer from the drawback that optimization for different flavins is required.

24

Recently, this easily accessible flavin and derivatives were used in our group for catalytic photooxidations.