Nature commonly employs the generation and capture of reactive intermediates as a strategy for the formation of complex products. However, formation of these species under mild conditions using traditional synthetic techniques can present a challenge. We have developed a biocatalyst-initiated method for the generation of reactive ortho-quinone methides under mild aqueous conditions. In this transformation, biocatalytic hydroxylation yields a benzylic alcohol product which, under the reaction conditions, is in equilibrium with the corresponding ortho-quinone methide. Interception of the ortho-quinone methide by a nucleophile or a dienophile allows for one-pot conversion of benzylic C–H bonds into C–C, C–N, C–O, and C–S bonds in a chemoenzymatic cascade. This method has enabled the synthesis of various natural product scaffolds.

Biocatalyst-initiated ortho-quinone methide generation and diversification

2019 Fall National Meeting

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