New Amines and Activation Modes in Asymmetric Aminocatalysis

Asymmetric aminocatalysis has become one of the most powerful strategies for the transformations of carbonyl substances over the past two decades.Here,we describe the research from our laboratory that significantly expands the horizon of aminocatalysis.It includes the development and application of cinchona-based primary amines,fruitful reactions based on HOMO-raising strategy,and the disclosure of amine/thiol double activation catalysis.

Electricity-driven enantioselective cross-dehydrogenative coupling of two C(sp^(3))-H bonds enabled by organocatalysis

An efficient and scalable electrochemical asymmetric protocol with metal-free catalysts and even without additional oxidants for the cross-dehydrogenative coupling reaction(CDC)of two C(sp^(3))-H bonds is reported.A series of aldehydes including natural products and various substrates containing C(sp^(3))-H bonds including xanthenes,acridines,cycloheptatrienes and even diarylmethane have been shown to undergo asymmetric CDC to afford a series of carbon-carbon bond coupling products with up to 94%yield and 98%ee.Mechanistic studies such as radical clock experiment suggest that the reaction proceeds via nucleophilic attack by enamine under electrochemical conditions.

Characterization and Monitoring of Transient Enamine Radical Intermediates in Photoredox/Chiral Primary Amine Synergistic Catalytic Cycle

Enamine-derived radicals are crucial intermediates in singly occupied molecular orbital(SOMO)catalysis.However,observing them directly is elusive and remains a long-standing challenge.Here,an advanced time-resolved electron paramagnetic resonance technique was employed to characterize and monitor the key intermediates in photoredox transformations by primary aminocatalysis on a microsecond timescale.The transient enamine radical cation,generated by single electron transfer(SET),and the deprotonated form ofα-imino radical intermediates were directly observed for the first time,both spectroscopically and kinetically.In reactions with styrene,enamine radical cation was found to be faster thanα-imino radical by one order of magnitude.This revealed the subtle role of deprotonation associated with secondary enamine radical cation in the photoredox transformations by primary aminocatalysis.

Asymmetric α-Alkylation of β-Ketocarbonyls via Direct Phenacyl Bromide Photolysis by Chiral Primary Amine

Enantioselective α-photoalkylation of β-ketocarbonyls without any external photosensitizer was described in this work. The photoalkylation reactions, enabled solely by a chiral primary amine catalyst, provided convenient constructions of all-carbon quaternary stereocenters with good activity and high enantioselectivity. Mechanism studies revealed α direct photolytic radical chain process under visible light irradiation.

Understanding how charge-charge interaction affects the stereochemistry of enamine fluorination by chiral primary amine catalysis

Electrostatic interaction, especially electrostatic attraction, usually plays critical roles in controlling the reactivity and selectivity in catalytic transformations;however, the like-charge repulsion, which is ubiquitous in physical systems, is rarely applied in reaction control. Herein we disclosed an unexpected like-charge repulsion induced enantio-control mode in primary aminecatalyzed fluorination reactions with 1-fluoro-2,4,6-trimethylpyridinium triflate. The ionic reaction works favorably in both highly polar(methanol) and non-polar(hexane) solvents, a seldom observed phenomenon in asymmetric catalysis. Erying plot analysis showed that an inversion temperature existed in Me OH, which was explained by the solvent-solute cluster model under different temperatures. Density functional theory(DFT) study and energy decomposition analysis(EDA) verified that the likecharge repulsion takes effect in polar solvent methanol, while in nonpolar solvents, the steric repulsion associated with ion-pair was found to be the major effect for the observed enantioselectivity.

One-pot synthesis of salicylaldehyde containing biaryl frameworks via an aminocatalytic Diels-Alder-retro-Diels-Alder cascade reaction of ynals with 2-pyrones

Salicylaldehyde containing biaryls are efficiently synthesized via an unprecedented amine promoted Diels-Alderretro-Diels-Alder cascade reaction of ynals with 2-pyrones in good yields.The reaction is instrumentally metalfree,operationally simple and mild,and tolerates a diverse array of functional groups.