Ru-Catalyzed C−H Hydroxylation of Tyrosine-Containing Di- and Tripeptides toward the Assembly of L-DOPA Derivatives

Abstract

The development of catalytic tools for the late-stage modification of amino acids within a peptide framework is a challenging task of capital importance. Herein, we report a Ru-catalyzed C(sp2)−H hydroxylation of a collection of Tyr-containing di- and tripeptides featuring the use of a carbamate as a removable directing group and PhI(OCOCF3)2 (PIFA) as oxidant. This air-compatible tagging technique is reliable, scalable and provides access to L-DOPA (L-3,4-dihydroxyphenylalanine) peptidomimetics in a racemization-free fashion. Density Functional Theory calculations support a Ru(II)/Ru(IV) catalytic cycle. (Figure presented.).