A Powerful Brønsted Acid Catalyst for the Organocatalytic Asymmetric Transfer Hydrogenation of Imines

Abstract

The catalytic hydrogenation of alkenes, ketones, and imines is arguably one of the most important transformations in chemistry. Powerful asymmetric versions have been realized that require metal catalysts or the use of a stoichiometric amount of metal hydrides [Eq. (1)]. [1] Although effective and industrially relevant catalytic asymmetric hydrogenations and transfer hydrogenations of olefins and ketones have been developed, the corresponding imine reductions, although potentially highly useful for the synthesis of enantiomerically pure amines, are less advanced.[2] Living organisms employ organic dihydropyridine cofactors such as nicotinamide adenine dinucleotide (NADH) in combination with enzyme catalysts for the reduction of imines.[3] Chemical transition metal catalyzed asymmetric imine reductions have also been developed, [4] and are used, in at least one case, on an industrial scale. [5] However, with the exception of interesting Lewis base catalyzed asymmetric imine hydrosilylations, [6] organocatalytic and metal-free variants were not known. Recently, we and MacMillan and co-workers developed an asymmetric transfer hydrogenation of a,b-unsaturated aldehydes catalyzed by a chiral ammonium salt by using Hantzsch esters as a biomimetic hydrogen source. [7] Rueping et al. [8] very recently reported the development of a novel and elegant approach using Hantzsch esters as the reducing reagent for the catalytic asymmetric reduction of imines using a chiral Brønsted acid catalyst previously developed by Akiyama et al.

Asymmetric Reductive Amination: Convenient Access to Enantioenriched Alkyl‐Alkyl or Aryl‐Alkyl Substituted α‐Chiral Primary Amines

“…À OR, À SO 2 R, or À NR 2 ; 5) asymmetric reductive amination of ketones using hydrides, [19] hydrogen, [20] or transfer hydrogenation [21] conditions; and 6) those methods employing organocatalysis. [22] In particular these methods are capable of synthesizing a-alkylaryl-substituted chiral amines, but few of them are capable of efficiently synthesizing a-alkyl-alkyl-substituted chiral primary amines in good overall yield and ee (Figure 2). …”

An Easy Entry to Optically Active Spiroindolinones: Chiral Brønsted Acid‐Catalysed Pictet–Spengler Reactions of Isatins

“…However, all the Brønsted acids 1 tested furnished poor enantioselectivity with the only exception of 1f [12] that allowed us Scheme 1. Catalytic asymmetric Pictet-Spengler reaction between tryptamines 2 and isatins 3.…”

“…During the optimisation process, [13] the same results in terms of catalyst activity and selectivity were in fact observed with reagent grade or dry solvents, with or without different desiccants (i.e., molecular sieves), in sharp contrast with most phosphoric acid 1-catalyzed asymmetric transformations. [9,10,12,15,17] Even more striking, the addition of increasing quantities of water to the mixture did not compromise the [a] Unless otherwise specified, the reactions were performed at 40 8C on a 0.1 mmol scale (2:3 = 1:1) with 10 mol% of (S)-1f.…”

Asymmetric Counteranion‐Directed Catalysis for the Epoxidation of Enals

“…[14][15][16] This catalyst together with tert-butyl hydroperoxide (tBuOOH) as oxidant converted cinnamaldehyde (1 a) into the desired 2,3-epoxyaldehyde 2 a in moderate yield, distereomeric ratio (d.r. 97:3), and enantiomeric ratio (e.r.…”