Chiral Brønsted acid catalyzed enantioselective intermolecular allylic aminations

Abstract

This paper describes an enantioselective intermolecular allylic amination catalyzed by a chiral Brønsted acid via a possible chiral contact ion pair intermediate. A variety of symmetrical or unsymmetrical allylic alcohols can be smoothly aminated to afford the desired products in moderate to high yields with good enantioselectivities and/or regioselectivities.

Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited

“…98 Enantioselective, intermolecular, Brønsted acid catalysed, direct allylic amination has been demonstrated, the approach is based on the concept of chiral ion-pair catalysis and relies on the assumed formation of a contact ion-pair with a chiral phosphoramide, although the only applied to highly π-active aromatic allylic alcohols. 99 The hydrogen borrowing mechanism removes chirality in a secondary alcohol substrate during the oxidation step, resulting a racemic product after reduction, however, asymmetric variants of the reaction are emerging with the use of a ruthenium catalyst and a chiral Josiphos ligand in the enantioselective preparation of β-aminoalcohols from racemic diols, via an asymmetric hydrogenation of an intermediate ketone. 100 The use of Ellman's chiral sulfinamide auxiliary enabled ruthenium catalysed preparation of enantiomerically enhanced amines from racemic secondary alcohols 101 and use of chiral phosphoric acids as an additive in combination with an iridium catalyst enabled preparation of chiral amines.…”

Recent Developments in Asymmetric Allylic Amination Reactions

“…For instance, the chiral triflimide catalyst 297 induces amination of the allylic alcohol 296 with 4-toluenesulfonamide to afford the allylic sulfonamide 298 in 60% yield and with 86% enantiomeric excess (Equation 25). 176 The enantiodetermining step is proposed to result from the amination of an intermediate chiral contact ion pair 299, which is formed from the ionization of the protonated allylic alcohol 296 using the chiral Brønsted acid catalyst. Nevertheless, the substrate scope is somewhat limited, since only electron-deficient 1,3-diarylprop-2-enols provide useful levels of enantiocontrol.…”

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

“…The reaction, catalyzed by catalyst 64, under mild conditions, is very efficient and selective, although with a narrow substrate scope (Figure 16b) [85]. A recent application is in the intermolecular allylic amination of allylic alcohols catalyzed by a phosphoramide, which leads to a variety of optically active allylic amines in good yields and ee values up to 94% [86]. The paper highlights that the amination site is mainly determined by electronic effects, and the reaction is supposed to occur at the carbon adjacent to the electron-rich aryl group owing to a carbocation intermediate involved in the process.…”