Copper-catalyzed asymmetric dearomatizing amination of 2-naphthols:Csp^(2)–N coupling via 1,3-reductive elimination

An efficient catalytic asymmetric dearomatizing amination of 2-naphthols and phenols catalyzed by N,N′-dioxide-copper(I)complex as a chiral catalyst was presented.A variety of optically activeβ-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained with high yield and enantioselectivity under mild reaction conditions.Mechanistic studies indicated that this Csp^(2)–N dearomatizing coupling proceeds via 1,3-reductive elimination of phenolate-Cu~Ⅲ-amino intermediate in five-membered ring transition states.The origin of enantioselectivity has also been elucidated based on density functional theory calculations.

Kinetic Resolution of Racemic 4-Substituted Chroman-2-ones Through Asymmetric Lactone Hydrogenation

Esters are abundant in natural and synthetic products and their conversion into primary alcohols holds great importance in fine chemical synthesis.However,achieving asymmetric hydrogenation(AH)of racemic esters with remote stereocenters via kinetic resolution(KR)remains a formidable challenge due to the difficulties associated with discerning spatially distant stereocenters.To address this issue,we have designed a hydroxy-assisted strategy that introduces a hydroxy group into racemicβ-aryl esters to facilitate hydrogenation and enhance chiral discrimination through a lactone form.By employing chiral Ir-SpiroPAP catalysts,we achieved exceptional AH of racemic 4-substituted chroman-2-ones,lactone form of ortho-hydroxylatedβ-aryl esters,via KR,resulting in impressive selectivity factor(s)values of up to 600.This approach exhibited significant efficacy for racemic chroman-2-ones containingβ-aryl,alkenyl,alkynyl,and alkyl groups,enabling the synthesis of chiralγ-aryl primary alcohols and the recovery of chiralβ-aryl esters or chroman-2-ones,typically difficult to access using existing methods.The scalability and broad synthetic applications of this method were exemplified by successfully synthesizing chiral drugs(R)-fesoterodine and enrasentan,alongside various chiral intermediates essential for producing chiral drugs and natural products.These promising results highlight the potential of this approach as a powerful tool for synthesizing valuable chiral compounds.

Iridium-Catalyzed Asymmetric Hydrogenation of Dialkyl Imines

Asymmetric hydrogenation of dialkyl imines to chiral amines is difficult because the two alkyls of imines are so similar in spatial and electronic structure that chiral catalysts are difficult to distinguish between them.In this study,we described an asymmetric hydrogenation of dialkyl imines by a chiral iridium catalyst containing spiro phosphine-amine-phosphine ligand.By precisely adjusting the chiral pocket of catalyst,a highly efficient catalyst was developed.Using this catalyst,a variety of dialkyl imines were hydrogenated to chiral amines with high yield and enantioselectivity.

Iron-Catalyzed Alkenylzincation of Internal Alkynes

The alkenylzincation of internal alkynes is an effective method for the synthesis of multi-substituted conjugated dienes;however,the current catalytic systems for this reaction are limited in terms of substrate scope and selectivity control,which restricts its practical applications.Herein,we report the first iron-catalyzed alkenylzincation of internal alkynes,which features mild conditions,simple operation,broad substrate scope (including aryl/alkyl,diaryl,and dialkyl acetylenes),excellent functional group tolerance (tolerating highly active functional groups such as ester,methylthio,amide,sulfonyl,cyano,etc.),and high activity (with a turnover number of up to 11500,the highest record for carbometallation reactions).Notably,the catalytic system described in this article also realized the highly selective vinylzincation of unfunctionalized internal alkynes as well as the alkenylzincation of unsymmetrical diarylacetylenes and dialkyl acetylenes,which have not been achieved with other catalytic systems reported in the literatures.The current study provides a highly selective access to synthetically important multi-substituted conjugated dienes.

Recent Progress of Asymmetric Catalysis from a Chinese Perspective

The precise construction of chiral molecules is a core research area in chemical science and technology.Among the plethora of reported synthetic methods,asymmetric catalysis has emerged as one of the most efficient and direct ways to obtain optically pure chiral compounds.This article mainly reviews the recent progress of asymmetric catalysis made by Chinese chemists from the following aspects:the development of new chiral ligands,transition metal-catalyzed asymmetric reactions,asymmetric organocatalytic reactions,and new strategies for asymmetric catalysis.This review does not intend to be comprehensive;only representative examples are selected to highlight the important progress made in this field.Finally,a brief outlook is given on the development of novel chiral ligands/catalysts,new enantioselective reactions,and their applications in chiral drugs and agricultural chemicals.

Diastereoselective and Enantioselective Nickel-Catalyzed Reductive Coupling of Imines and Unactivated Alkenes

Herein we report a method for highly diastereoselective and enantioselective nickel-catalyzed reductive coupling of imines and unactivated alkenes.A monodentate chiral spiro phosphoramidite ligand is the key to controlling the enantioselectivity.This efficient,straightforward method allows for the construction of chiral benzocyclic and indole-fused cyclic amines with two contiguous stereogenic centers in good yields from readily accessible starting materials.

Design and Synthesis of Spirochroman-2-on-4,1'-indan-7'-ol and Its Application for Synthesizing Chiral Monophosphinite Ligands

The design and synthesis of spirochroman-2-on-4,1'-indan-7'-ol(SCIOL)and its application for synthesizing chiral monophosphinite ligands are reported.The synthesis features a tandem double Friedel-Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCiOL was obtained via 6 steps with a total yield of 44.5%.Using an inclusion resolution with N-benzylcinchonidinium chloride,the optical SCiOL could be obtained in good yields on a gram scale.The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity(up to 94%ee)in the rhodium-catalyzed asymmetric hydrogenation of N-acetyl dehydroamino esters.These outcomes highlight the significant potential of SCiOLas a useful framework forthedevelopment of chiral spiro ligands.

Ligand-Enabled Ni-Catalyzed Enantioselective Hydroarylation of Styrenes and 1,3-Dienes with Arylboronic Acids

We report an enantioselective hydroarylation reaction of styrenes and 1,3-dienes with arylboronic acids catalyzed by nickel complexes bearing chiral spiro amino phosphine ligands.The reaction serves as an efficient,straightf orward,and mild method for the preparation of enantio enriched 1,1-diarylalkanes,which are important building blocks for the synthesis of many biologically active molecules.This redox neutral reaction uses only catalytic amounts of the reagents and is,therefore,atom economical and environmentally benign.

Electrochemical Synthesis of Sulfonyl Fluorides with Triethylamine Hydrofluoride

Hydrofluoride is an industry-preferred fluoride source,and finds extensively application to manufacture diverse fluoro chemicals.The Et3N-3HF complex is a liquid HF with improve safety.In this work,we report electrochemical synthesis of a series of sulfonyl fluoride with Et3N-3HF as fluoride source.The sulfinic salt is a smell-less,non-volatile,and air-stable sulfur source in this reaction.With the combination of Et3N-3HF and aryl/alkyl sulfinic salt,the sulfonyl fluorides are achieved without the use of external oxidant.In addition,we demonstrate further advantage in a tandem reaction involving Pd-catalyzed C—S cross-coupling and formation of S—F bond.A variety of functional groups including amino acids,heterocycles,halides are well tolerated.

Synthesis of Chiral α-Benzyl-β^(2)-hydroxy Carboxylic Acids through Iridium-Catalyzed Asymmetric Hydrogenation of α-Oxymethylcinnamic Acids

An asymmetric hydrogenation of α-oxymethylcinnamic acids was developed by using chiral spiro phosphineoxazoline/iridium complexes as catalysts to prepare β^(2)-hydroxycarboxylic acids with high reactivity(TON up to 2000)and excellent enantioselectivity(up to 99.5%ee).By using this highly efficient asymmetric hydrogenation as a key step,a concise total synthesis of natural product homoisoflavone(S)-(+)-4 was accomplished.

Nickel-Catalyzed Regio-and Enantioselective Hydroarylation of 1,3-Dienes with Indoles

The regio-and enantioselective functionalization of 1,3-dienes has become a powerful tool for the synthesis of allylic compounds,yet it remains a challenge for aliphatic dienes.Herein,we report a nickel-catalyzed asymmetric hydroarylation reaction of aliphatic and aromatic dienes with indoles to afford chiral indole derivatives.