Diastereoselective Synthesis of Functionalized Indolines Using in situ Generated Allyl Boronic Species

Abstract

A new three-component coupling protocol for preparation of functionalized indolines, with a high degree of diastereoselectivity, has been developed. The protocol is based on the in situ homologation of vinyl boronic acids to allylboronic acids, using TMSCHN2 as carbon source, and subsequent coupling reaction with indoles to give 2-substituted indolines. The scope of the method was exemplified in several examples.

Mechanism of Asymmetric Homologation of Alkenylboronic Acids with CF3-Diazomethane via Borotropic Rearrangement

“…An interesting method for the homologation of organoboronates is based on the application of diazomethane derivatives. The first reactions were reported by the groups of Barluenga, Ley, , Molander, and Wang on the homologation of alkenyl- and other boronic acids with diazomethane derivatives for the formation of a wide variety of allyl- and other boronic acids. ,− Due to their high versatility for the synthesis of complex target molecules (e.g., via enantioselective allylboration or cross-coupling reactions), organoboronic acids are obviously some of the most used reagents in advanced organic synthesis . Noteworthily, the above-mentioned methodologies for the homologation of organoboronic acids with diazomethane derivatives provide only achiral products or racemates.…”

“…The mechanism shown in Scheme has been proposed for the reaction . In analogy to other BINOL-catalyzed allylboration reactions developed by the group of Szabo, − it was suggested that the ethanol additive helps in the prevention of undesired side reactions, namely, while alkenylboroxine 1 readily reacts with diazo compounds, ,, the alkyl boronic ester 6 , formed by the addition of ethanol, was not expected to be reactive toward these derivatives. Due to the dynamic covalent bonding ability of boron, the alkyl boronic ester 6 is expected to undergo transesterification with ( R )-I-BINOL ( 3 ) to form chiral alkenylboronate 7 .…”