biostudies-literatureZhou BDivision of ChemistryEuropean Research Council8361-8365https://www.ebi.ac.uk/biostudies/studies/S-EPMC11459507biostudies-literatureUnknown26(39)A straightforward and general strategy for the catalytic asymmetric synthesis of β³-tryptophans by carboxylic-acid-directed intermolecular C-H amination has been developed. The iron-catalyzed C-H amination of 3-indolepropionic acids with BocNHOMs (Boc, <i>tert</i>-butyloxycarbonyl; OMs, methylsulfonate) in the presence of the base piperidine provides N-Boc-protected β³-tryptophans in a single step with high enantiomeric excess (ee) of up to >99%. Mechanistic experiments and density functional theory calculations support a mechanism through carboxylate-directed iron-mediated C(sp³)-H nitrene insertion. The method incorporates two key sustainability criteria: the use of iron as an abundant, non-toxic, and environmentally benign metal, along with the achievemeOrganic lettersβ&lt;sup&gt;3&lt;/sup&gt;-Tryptophans by Iron-Catalyzed Enantioselective Amination of 3-Indolepropionic Acids.PMC11459507CHE-2338438883212Ivlev SIMeggers EZhou BIh MIYao SHemming MChen Sfalseβ&lt;sup&gt;3&lt;/sup&gt;-Tryptophans by Iron-Catalyzed Enantioselective Amination of 3-Indolepropionic Acids.A straightforward and general strategy for the catalytic asymmetric synthesis of β³-tryptophans by carboxylic-acid-directed intermolecular C-H amination has been developed. The iron-catalyzed C-H amination of 3-indolepropionic acids with BocNHOMs (Boc, <i>tert</i>-butyloxycarbonyl; OMs, methylsulfonate) in the presence of the base piperidine provides N-Boc-protected β³-tryptophans in a single step with high enantiomeric excess (ee) of up to >99%. Mechanistic experiments and density functional theory calculations support a mechanism through carboxylate-directed iron-mediated C(sp³)-H nitrene insertion. The method incorporates two key sustainability criteria: the use of iron as an abundant, non-toxic, and environmentally benign metal, along with the achieveme2024-01-01T00:00:00Z2024 Oct2025-04-04T01:54:36.684Z2025-04-04T01:54:36.684ZS-EPMC114595073931175910.1021/acs.orglett.4c03130