Pd-Catalyzed Asymmetric Allylic C—H Functionalization

Comprehensive Summary Pd-catalyzed asymmetric allylic C—H functionalization has emerged as a powerful tool to access chiral,densely functionalized molecules from easily accessible alkenes,enabling the increase of the step-or atom-economy by minimizing functional group manipulations for preparing allylating reagents.Due to the inadequacy of stereoselection strategies,the asymmetric allylic C—H functionalization is still in the early stage.In this essay,we will describe our journey to identification of asymmetric catalytic systems,mechanism of allylic C—H activation,control of stereo-and regioselectivity,and applications in asymmetric synthesis.

Cooperative Dual Organocatalytic Asymmetric Decarboxylative[4+3]Annulations with Benzoxazinanones

The cooperative catalysis of an achiral Lewis base and a chiral N-heterocyclic carbene(NHC)enables a highly enantioselective[4+3]annulation of benzoxazinanones with isatin-derived enals.DMAP serves as a nucleophilic Lewis base to promote decarboxylation of benzoxazinanones,which leads to azaortho-xylylene intermediates that undergo[4+3]annulations with NHC-bound homoenolates.This method breaks the substrate scope limitation of transition-metal-catalyzed variants,thus a broader range of benzoxazinanones are tolerated,and provides a straightforward entry to enantioenriched spirooxindoles in high structural diversity.

Palladium-catalyzed asymmetric allylic C–H alkylation of 1,4-dienes and glycine Schiff bases

A highly regio-and enantioselective allylic C–H alkylation of 1,4-dienes with glycine Schiff bases has been established by chiral palladium-phosphoramidite catalysis. This reaction can proceed under mild conditions and tolerate a wide scope of 1,4-dienes,delivering structurally diverse chiral β-branched α-amino acid surrogates in moderate to high yields and with high levels of regio-, Z/E-, diastereo-and enantioselectivities.

Atroposelective sp3 C—H Coupling for Kinetic Resolution of Thioanilide Atropisomers

A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite ligand,leading to both enantioenriched atropisomeric arylation thioanilides(up to 99%ee)and N-Me atropisomeric thioanilides(up to 99%ee),simultaneously.The remained enantioenriched substrates can be arylated again by using an achiral anionic ligand to give the enantiomer with the opposite configuration.

Palladium‐Catalyzed Asymmetric Dihydroxylation of 1,3‐Dienes with Catechols

Summary of main observation and conclusion A palladium‐catalyzed asymmetric dihydroxylation of 1,3‐dienes with catechols is developed using chiral pyridinebis(oxazoline) ligands. Various chiral 2‐substituted 1,4‐benzodioxanes could be synthesized with moderate to high yields and enantioselectivities from readily available starting materials. The reaction is proposed to proceed through a cascade Wacker‐type hydroxypalladation/asymmetric allylation process.

Platinum-Catalyzed Allylic C-H Alkylation with Malononitriles

The direct functionalization of allylic C-H bonds is distinguished by enabling rapid assembly of structural complexity from simple molecules.Although Pd-catalyzed allylic C-H functionalization has been extensively studied,the discovery of new catalytic systems remains fairly underdeveloped.Here,we disclose a Pt-catalyzed allylic C-H alkylation of a wide range of α-alkenes by using phosphoramidites as ligands and malononitriles as alkylating reagents.Notably,the combination of chiral ureacatalyzed Michael addition and Pt-catalyzed allylic C-H alkylation can serve as an efficient protocol to access chiral tetrahydropyran with high levels of diastereo-and enantioselectivity.Mechanistic studies suggest that the Pt-catalyzed allylic C-H activation proceeds through a concerted proton and two-electron transfer process,which is analogous to transition state geometries of Pd catalysis.

Access to chiral homoallylic vicinal diols from carbonyl allylation of aldehydes with allyl ethers via palladium-catalyzed allylic C-H borylation

Chiral homoallylic vicinal diols are found in many bioactive compounds and are among the most versatile functional groups in organic chemistry. Here, we describe an asymmetric carbonyl allylation of aldehydes with allyl ethers proceeding via allylic C-H borylation enabled by palladium and chiral phosphoric acid sequential catalysis, providing facile access to homoallylic vicinal anti-diols in high yields and with excellent stereoselectivity. This protocol enables the total synthesis of aigialomycin D to be finished within 7 steps.

Chiral aldehyde catalysis: a highly promising concept in asymmetric catalysis

Asymmetric organocatalysis has been a robust tool for manufacturing optically active molecules,in addition to asymmetric metal and bioeatalysis .The development of new concepts and catalysts to enable the creation of efficient synthetic methods has been a longstanding activity in this field.During the last decades,a diverse spectrum of chiral organocatalysts,including ketones,amine,Bronsted acids and bases,phase-transfer catalysts,and nucleophilic catalysts,have been developed,culminating in a large number of transformations enabling the efficient construction of optically active natural and unnatural compounds.

Photoinduced and palladium-catalyzed hydrogen atom transfer triggered 1,2-difunctionalization of 1,3-dienes with hydroxamides

The discovery of novel catalysis modes to generate a significant increase in structural complexity from readily available reactants is a fundamental goal in modern organic synthesis.Here,we report a photoinduced palladium-catalyzed hydrogen atom transfer triggered 1,2-difunctionalization of conjugated dienes.Without the employment of exogeneous photosensitizers and external oxidants,the cascade reaction realized the integration of remote functionalization of various C(sp^(3))-H bonds and selective difunctionalization of 1,3-dienes with 100% atom efficiency,allowing for the synthesis of structurally diverse amides with up to 90% yields.Given the prevalence of amides in pharmaceuticals and natural products,the current protocol has provided an efficient means to access highly functionalized amides from readily available carboxylic acid derivatives and 1,3-dienes.

Nickel-Catalyzed Enantioselective Desymmetrizing Aza-Heck Cyclization of Oxime Esters

Densely functionalized chiral nitrogen-containing heterocycles are ubiquitous in bioactive synthetic compounds and natural products.Herein,we report a nickel(Ni)-catalyzed enantioselective desymmetrizing aza-Heck cyclization of oxime esters with a commercially available chiral pyridinebis(oxazoline)(pybox)ligand.This reaction proceeds under mild reaction conditions,tolerates various functional groups,and leads to chiral 2-substituted-3,7a-dihydro-3aH-indoles.