Iridium‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene Succinimides

Abstract

Not to be out PhOXed! The title reaction provides a new approach to chiral succinimide derivatives with excellent yields and ee values by using a low catalyst loading (0.05 mol %) and mild reaction conditions. Chiral 3‐benzyl pyrrolidines and 1‐hydroxypyrrolidine‐2,5‐diones, important structural motifs in natural products and pharmaceuticals, could be readily prepared. BARF−=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate.

Cobalt‐Catalyzed Asymmetric Hydrogenation of C=N Bonds Enabled by Assisted Coordination and Nonbonding Interactions

“…[3a-d, 5a,b, 7a] Compared to other inexpensive transition metals,c obalt can partake in redox (Co 0 /Co II ,C o I /Co III )a nd redox-neutral (Co I and Co II )c atalytic cycles,a nd stably coordinate with both chiral N-and P-donor ligands,w hich has led, therefore, to cobalt being utilized in various enantioselective transformations. Continuing our pursuit of chiral nitrogen-containing compounds through asymmetric hydrogenation, [11] and being encouraged by our recent work on the nickel-catalyzed asymmetric hydrogenation of C=Nbonds, [7a] herein we disclose for the first time the efficient cobaltcatalyzed asymmetric hydrogenation of C=Nb onds enabled by assisted coordination and nonbonding interactions (Scheme 1). [6] However,t he inherent characteristics of these first row transition metals results in them having ar elatively low ability to activate hydrogen and substrates,which has resulted in two problems: 1) the catalytic productivity is generally low (the highest TON reported is 1667 [6g] )and 2) the substrate scope is limited (the Co-catalyzed asymmetric hydrogenation of ketimines is ag reat challenge).…”

Rh‐Catalyzed Chemo‐ and Enantioselective Hydrogenation of Allylic Hydrazones

“…[8] Although excellent enantioselectivities (up to 99 % ee)h ave been obtained, this approach has an evident limitation with regard to the synthesis of chirala rylvinyl amines.A na lternativer oute involvesachemo-ande nantioselectiveh ydrogenation of allylic ketimines, which can be used to prepare chiral arylvinyl amines.H owever,o btaining both high chemo-and enantioselectivity still remains challenging using this particularp athway. [9] During our investigations concerning asymmetrich ydrogenation reactions, [10] we discovered ar oute for the chemo-and enantioselective hydrogenation of allylic ketones, assistedb ya namido directingg roup for the efficients ynthesis of a-amido ketones. [10g] Using as imilar strategy, [11] we herein report the chemo-and enantioselective hydrogenation of N-amido arylvinyl ketimines (allylic hydrazones) for the efficient synthesis of chiral N-amido allylic amines( allylic hydrazines) ( Figure 1).…”

“…As eries of frequently used solvents weret hen tested and it was found that dichloromethane gave the best enantioselectivity of 97 % ee (entries 5-9). Screening of other commonly used diphosphine ligandsg ave poorer results compared to BenzP* (entries [10][11][12][13]. To increase the chemoselectivity,w ei nvestigated other factors which may influence this reaction.…”

Exocyclic Olefinic Maleimides: Synthesis and Application for Stable and Thiol‐Selective Bioconjugation

“…We report that exocyclic olefinic maleimides are attractive scaffolds for site‐specific bioconjugation as they react specifically with thiols at physiological conditions to form stable linkages which resist thiol‐exchange‐mediated breakdown. In addition to bioconjugation applications, the advances in the synthesis of exocyclic olefinic maleimides reported herein will facilitate realization of the tremendous potential of these scaffolds for the preparation of heterocyclic compounds as underscored by their previous use for the synthesis of substituted maleic anhydrides, endocyclic olefinic maleimides, succinimides, and pyrrolidines, and encourage exploration of their considerable therapeutic potential…”