Aerobic oxyfunctionalization of alkynes by a bioinspired flavin–metal ion photocatalytic system†

Abstract

The one-electron oxidation of alkynes and the subsequent nucleophilic addition represent a straightforward way to value-added α-keto ketals, especially the less-known oxo-spiroketals, which are promising structural scaffolds in natural products and pharmaceuticals. However, this strategy remains to be developed due to the high oxidation potential of electron-deficient CC bonds and the challenge of controlling regioselectivity in the nucleophilic addition step. In particular, oxo-spiroketals have yet to be synthesized via the oxyfunctionalization of alkynes. Herein, we report the photocatalytic oxyfunctionalization of alkynes with electron-withdrawing groups to afford α-keto ketals with alcohols and molecular oxygen using riboflavin tetraacetate (RFT) as a powerful photoredox catalyst by binding to two scandium ions ([RFT-2Sc³⁺]). For unsymmetrical di-aryl acetylenes and phenyl alkyl acetylenes, excellent regioselectivity is perhaps achieved due to the stability of the final ketal products, as well as the negative charge distribution on the adjacent carbon of the CC bond induced by electron withdrawing groups at the para- or meta-position. Di-aryl acetylenes with ortho-substitutions tend to have poor site-selectivity, which may be due to unfavorable steric hindrance. Additionally, the synthesis of benzannulated oxo-5,6- and oxo-6,6-spiroketal and unprecedented oxo-6,7-spiroketal in nature has been achieved for the first time using alkynediol substrates. Mechanistic studies, including control experiments, and Hammett and spectroscopy analyses, have revealed that the electron transfer from alkynes to the excited [RFT-2Sc³⁺]* complex is the key step in the oxyfunctionalization of alkynes. Such a flavin–metal ion photocatalytic system provides a green approach to valuable multioxygen-containing motifs.