Ruthenium‐Catalyzed Enantioselective Synthesis of β‐Amino Alcohols from 1,2‐Diols by “Borrowing Hydrogen”

Abstract

Enantioselective synthesis of β‐amino alcohols from 1,2‐diols by the use of [RuCl2(p‐cymene)]2/(S,R)‐JOSIPHOS catalysis was developed. Several 1,2‐diols were treated with secondary amines to afford the corresponding optically active β‐amino alcohols in up to 99 % yield with 77 % ee.

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

“…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. 102 Given the amount of progress made in all alcohol activation approaches it is surprising to find few published reports of scale-up of direct substitution approaches towards the preparation of pharmaceutically relevant substrates.…”

Transition‐Metal‐Free Hydrogen Autotransfer: Diastereoselective N‐Alkylation of Amines with Racemic Alcohols

“…Williams and co‐workers also used a chiral amine substrate in a Ru‐catalyzed amination of alcohols with retention of chirality in the product, albeit with no new chiral center generated . In 2013, Oe and co‐workers reported the first asymmetric alkylation of achiral amines with racemic alcohols with a chiral Ru catalyst, affording moderate ee values (<70 %) . A major breakthrough was made by Zhao and co‐workers in 2014, who showed that chiral amines of up to greater than 99 % ee can be formed by reacting achiral amines with racemic alcohols using a chiral Ir catalyst in conjunction with a chiral phosphoric acid (Figure ) .…”

Ruthenium-Catalyzed Amination of Secondary Alcohols Using Borrowing Hydrogen Methodology

“…7 Similarly, Oe reported the regioselective amination of 1-phenyl-1,2-ethanediol with secondary amines (5 mol% Ru and ( S,R )-Josiphos). 8 …”