Larock Indolization of Chloroanilines for the Synthesis of Noncanonical Tryptophans and Macrocyclic Compounds

The Larock indolization has served as a powerful method to access substituted indoles, tryptophans and naturally occurring alkaloids containing an indole nucleus. While the reaction has been well studied on o-iodo- and o-bromoanilines, the use of the more accessible o-chloroanilines remains elusive, especially in the structurally complex contexts of amino acids, peptides and biologically active compounds. We report herein a general and practical protocol for the Larock indolization of o-chloroanilines to access structurally diverse noncanonical tryptophans and indole-embedded macrocycles.