Asymmetric Synthesis of β²-Tryptophan Analogues via Friedel–Crafts Alkylation of Indoles with a Chiral Nitroacrylate

Abstract

The asymmetric Friedel-Crafts alkylation of various indoles with a chiral nitroacrylate provides optically active β-tryptophan analogues after reduction of the nitro group and removal of the chiral auxiliary. This reaction generally occurs in good yield and high diastereoselectivity (up to 90:10).

Pd(II)-Catalyzed Direct γ-C(sp3)-H Arylation between Free β2-Amino Esters and β3-Amino Esters and Aryl Iodides Using a Catalytic Transient Directing Group

“…β-amino acids (β-AAs) are significant and rewarding functional moieties in various peptides, peptidomimetics, proteins, antibiotics, and other biologically active compounds and have been increasingly used in the pharmaceutical, agrochemical, and healthcare industries. , Traditionally, the synthesis of β-AAs and their derivatives was mainly carried out by the carbonylation of enamines . In recent years, using a transition-metal-catalyzed direct C–H functionalization strategy to modify simple amino acids is an efficient and valuable route to obtain unnatural amino acids .…”

β‐Nitroacrylates: A Versatile and Growing Class of Functionalized Nitroalkenes

“…Tryptophan analogues play a pivotal role in the synthesis of many important targets such as peptidomimetics, natural products and a large variety of biologically active molecules . In 2011 Calmès et al . investigated the Friedel–Crafts reaction of the chiral β‐nitroacrylate 1f with a series of substituted indoles 77 to furnish the chiral adducts 78 which, in turn, were converted over three steps into the corresponding N ‐Fmoc‐protected tryptophan analogues 79 (Scheme ).…”

Enantioselective Copper(II)/Box‐Catalyzed Synthesis of Chiral β3‐Tryptophan Derivatives

“…Using this method β 2 ‐ and β 2,2 ‐tryptophan derivatives were obtained by the reaction of indoles and Michael acceptors such as β ‐nitroacrylates and α‐substituted β ‐nitroacrylates. For asymmetric induction chiral β ‐nitroacrylate was used in the case of β 2 ‐derivatives, whereas either Ni (II) chiral complex or chiral phosphoric acid were employed as a catalyst to prepare optically active β 2,2 ‐derivatives.…”