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

Abstract

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( sp 2 )−H hydroxylation of a collection of Tyr‐containing di‐ and tripeptides featuring the use of a carbamate as a removable directing group and PhI(OCOCF 3 ) 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. magnified image