Dynamic Kinetic Asymmetric Reductive Amination: Synthesis of Chiral Primary β‐Amino Lactams

Abstract

Scheme 2. Larger-scale synthesis and synthetic utility of product 2a. Boc = tert-butoxycarbonyl, DCM = dichloromethane.

Ruthenium‐Catalyzed Direct Reductive Amination of Carbonyl Compounds for the Synthesis of Amines: An Overview

“…For the synthesis of enantiomerically pure primary β‐amino lactams, Lou and colleagues created a Ru‐catalyzed ARA of racemic β‐keto lactams with ammonium acetate and hydrogen in 2018 (Scheme 24). [60] The best‐catalyzed reaction was obtained by using [Ru(OAc) 2 (S)‐SegPhos] as the catalyst, and AcOH as the additive in methanol solvent at 80 °C for 20 h. To maintain the reactivity and stereoselectivity of the reaction to furnish β‐keto lactams, the acid additive is necessary.…”

Practical N-alkylation via homogeneous iridium-catalyzed direct reductive amination

“…As a result, frequently those catalytic procedures suffer narrow substrate scope, requirement of excess additives, high catalyst loading, high reaction temperature and/or synthetically demanding catalytic complexes and ligands. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] To date, successful universal catalytic systems with broad substrate scope are extremely scarce. [41][42][43][44][45][46] In this regard, highly efficient and practical homogeneous catalytic systems for more functional group tolerating with low catalyst loading and simplified and inexpensive ligands are immensely desired.…”

Ligand Backbone Influence on the Enantioselectivity in the Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination of Ketones with NH3/H2 Using Binaphthyl‐Substituted Phosphines

“…By using stoichiometric amounts of ammonium formate and a Ru−BINAP catalyst, [2] NH 4 OAc/H 2 and a Ru−C 3 −TunePhos catalyst, [3] or NH 4 Cl/H 2 and Ru−dtbm−Segphos, [4] ee values of up to 94 % could be achieved for simple aryl−alkyl−ketones. For substrates bearing directing groups, e. g., sterically hindered aryl−ketones with o ‐phenolic substituents and the presence of a Ru−BINAP catalyst combined with NH 4 OAc/H 2 /Ti(OPr) 4 , [5] β ‐keto lactams using a Ru−SegPhos/PhCO 2 NH 4 /AcOH/H 2 system, [6] or 2‐acetyl‐6‐susbstituted pyridines using a Ru−BINAP/CF 3 CO 2 NH 4 /H 2 system [7] even ee ’s up to 99 % are possible. Despite these high enantioselectivities for the synthesis of primary chiral amines, these protocols still suffer from stoichiometric salt waste formation reducing the atom efficiency.…”