Employing Small Polyfunctionalized Molecules for a Diastereoselective Synthesis of Highly Substituted Indolines

Abstract

An efficient approach has been developed for the diastereoselective synthesis of 1,2,3‐trisubstituted indolines. The reaction sequence includes the highly diastereoselective reductive amination of 2‐oxo‐1,3‐propanediols, which are prepared by postfunctionalization of Morita–Baylis–Hillman (MBH) adducts, to give substituted 2‐amino‐1,3‐propanediols with an anti relative configuration. A subsequent intramolecular palladium‐catalyzed Buchwald coupling reaction provided the 1,2,3‐trisubstituted indolines in 47–82 % yield. The preference for the anti diastereomer was investigated by Gibbs free energy diagrams and applying theoretical calculations at the M06–2X/6‐31+G** level.

Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction

“…A state-of-the-art method toward functionalized indolines utilizes well-established homogeneous coupling reactions. Two major approaches are predominantly found in the literature, namely the intra- and intermolecular [3 + 2] heteroannulation of ortho -iodoanilines (Scheme , section 1a) − and the cyclization of ortho -allylanilines (Scheme , section 1b). − In almost all these methods, temperatures above 80 °C are applied significantly hampering the group tolerance of the approaches. Additionally, most of these procedures lead to 2-substituted indolines due to the directing effect of the amine group.…”

Preparation of tetrahydro-1H-xanthen-1-one and chromen-1-one derivatives via a Morita-Baylis-Hillman/oxa-Michael/elimination cascade

“…[1][2][3] Due to the high functionalization degree of the adducts obtained from MBH reactions, they have been employed in the synthesis of a variety of heterocycles. [4][5][6][7][8][9] Among the examples of oxygenated heterocycles, a class that has not been particularly explored is the tetrahydroxanthenones and chromenones and the possibility of obtaining them from the reaction of 2-hydroxybenzaldehydes and cyclic enones. These compounds are important heterocycles with a wide range of biological activities such as antimicrobial, antifungal and anticancer.…”