Biocatalyst-Initiated Ortho-Quinone Methide Formation and Derivatization [post]

Tyler Doyon, Jonathan Perkins, Summer A. Baker Dockrey, Kevin Skinner, Paul M. Zimmerman, Alison Narayan
2019 unpublished
Generation of reactive intermediates and interception of these fleeting species in a cascade is a common strategy employed by Nature. However, formation of these species under mild conditions using traditional synthetic techniques can present a challenge. Here, we demonstrate the utility of biocatalysis in generating ortho-quinone methide intermediates under aqueous conditions and at reduced temperatures. Specifically, we applied an α-ketoglutarate-dependent non-heme iron enzyme, CitB, in the
more » ... yme, CitB, in the selective modification of benzylic C–H bonds of ortho-cresol substrates to afford 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.
doi:10.26434/chemrxiv.7828769.v1 fatcat:uvzdxfn7w5eqbcxipcjepn6soq