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1. Asymmetric allylic substitution–isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer

   https://doi.org/10.1039/D0SC02828B  

   Sun, Chao ; Qi, Xiaotian ; Min, Xiao-Long ; Bai, Xue-Dan ; Liu, Peng ; He, Ying ( September 2020 , Chemical Science)

   null (Ed.)

   Axially chiral enamides bearing a N–C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we report the first enantioselective synthesis of axially chiral enamides via a highly efficient, catalytic approach. In this approach, C(sp 2 )–N bond formation is achieved through an iridium-catalyzed asymmetric allylation, and then in situ isomerization of the initial products through an organic base promoted 1,3-H transfer, leading to the enamide products with excellent central-to-axial transfer of chirality. Computational and experimental studies revealed that the 1,3-H transfer occurs via a stepwise deprotonation/re-protonation pathway with a chiral ion-pair intermediate. Hydrogen bonding interactions with the enamide carbonyl play a significant role in promoting both the reactivity and stereospecificity of the stepwise 1,3-H transfer. The mild and operationally simple formal N -vinylation reaction delivered a series of configurationally stable axially chiral enamides with good to excellent yields and enantioselectivities. 

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2. Chiral Brønsted acid-controlled intermolecular asymmetric [2 + 2] photocycloadditions

   https://doi.org/10.1038/s41467-021-25878-9  

   Sherbrook, Evan M. ; Genzink, Matthew J. ; Park, Bohyun ; Guzei, Ilia A. ; Baik, Mu-Hyun ; Yoon, Tehshik P. ( September 2021 , Nature Communications)

   Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. Recently, it has become recognized that the photophysical properties of simple organic substrates can be altered upon coordination to Lewis acid catalysts, and that these changes can be exploited in the design of highly enantioselective catalytic photoreactions. Chromophore activation strategies, wherein simple organic substrates are activated towards photoexcitation upon binding to a Lewis acid catalyst, rank among the most successful asymmetric photoreactions. Herein, we show that chiral Brønsted acids can also catalyze asymmetric excited-state photoreactions by chromophore activation. This principle is demonstrated in the context of a highly enantio- and diastereoselective [2+2] photocycloaddition catalyzed by a chiral phosphoramide organocatalyst. Notably, the cyclobutane products arising from this method feature atrans-cisstereochemistry that is complementary to other enantioselective catalytic [2+2] photocycloadditions reported to date.

    

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3. Catalytic asymmetric transformations of racemic α-borylmethyl-( E )-crotylboronate via kinetic resolution or enantioconvergent reaction pathways

   https://doi.org/10.1039/d1sc04047b  

   Gao, Shang ; Liu, Jiaming ; Chen, Ming ( October 2021 , Chemical Science)

   We report herein catalytic asymmetric transformations of racemic α-borylmethyl-( E )-crotylboronate. The Brønsted acid-catalyzed kinetic resolution–allylboration reaction sequence of the racemic reagent gave ( Z )-δ-hydroxymethyl- anti -homoallylic alcohols with high Z -selectivities and enantioselectivities upon oxidative workup. In parallel, enantioconvergent pathways were utilized to synthesize chiral nonracemic 1,5-diols and α,β-unsaturated aldehydes with excellent optical purity. 

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4. Organocatalytic enantioselective dearomatization of thiophenes by 1,10-conjugate addition of indole imine methides

   https://doi.org/10.1038/s41467-021-25165-7  

   Li, Xingguang ; Duan, Meng ; Yu, Peiyuan ; Houk, K. N. ; Sun, Jianwei ( December 2021 , Nature Communications)

   Abstract Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control. 

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5. Asymmetric Photocatalysis Enabled by Chiral Organocatalysts

   https://doi.org/10.1002/cctc.202101292  

   Yao, Wang ; Bazan‐Bergamino, Emmanuel A. ; Ngai, Ming‐Yu ( November 2021 , ChemCatChem)

   Visible‐light photocatalysis has advanced as a versatile tool in organic synthesis. However, attaining precise stereocontrol in photocatalytic reactions has been a longstanding challenge due to undesired photochemical background reactions and the involvement of highly reactive radicals or radical ion intermediates generated under photocatalytic conditions. To address this problem and expand the synthetic utility of photocatalytic reactions, a number of innovative strategies, including mono‐ and dual‐catalytic approaches, have recently emerged. Of these, exploiting chiral organocatalysis, such as enamine catalysis, iminium‐ion catalysis, Brønsted acid/base catalysis, andN‐heterocyclic carbene catalysis, to induce chirality transfer of photocatalytic reactions has been widely explored. This Review aims to provide a current, comprehensive overview of asymmetric photocatalytic reactions enabled by chiral organocatalysts published through June 2021. The substrate scope, advantages, limitations, and proposed reaction mechanisms of each reaction are discussed. This review should serve as a reference for the development of visible‐light‐induced asymmetric photocatalysis and promote the improvement of the chemical reactivity and stereoselectivity of these reactions.

    

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