The selective tagging
of amino acids within a peptide framework
while using atom-economical C–H counterparts poses an unmet
challenge within peptide chemistry. Herein, we report a novel Pd-catalyzed
late-stage C–H acylation of a collection of Tyr-containing
peptides with alcohols. This water-compatible labeling technique is
distinguished by its reliable scalability and features the use of
ethanol as a renewable feedstock for the assembly of a variety of
peptidomimetics.
Despite the widespread use of cross-dehydrogenative couplings in modern organic synthesis, mechanistic studies are still rare in the literature and those applied to α-amino carbonyl compounds remain virtually unexplored. Herein the mechanism of a Co-catalyzed CDC of N-aryl glycinates with indoles is described. DFT studies supported the formation of an imine type intermediate as the more plausible transient electrophilic species. Likewise, key information regarding the role of the N-aryl group and free NH motif within the reaction outcome has been gained, which may set the stage for further developments in this field of expertise.
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.
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