Cu/chiral phosphoric acid-catalyzed radical-initiated asymmetric aminosilylation of alkene with hydrosilane

The catalytic radical-initiated asymmetric 1,2-aminosilylation of alkene with a hydrosilane under Cu(I)/CPA cooperative catalysis has been developed.This method features the use of hydrosilane as the reductive radical precursor,enabling efficient access to skeletally diverse silicon-containing azaheterocycles including pyrrolidine,indoline and isoindoline bearing anα-tertiary stereocenter with high enantioselectivity.The key to the success includes the use of Cu(I)/CPA cooperative catalyst system and theβ-silicon effect of the silyl group to stabilize the in situ generated carbocation intermediate.

Synthesis of Chiral Amino Cyclic Phosphoric Acids

Chiral amino cyclic phosphoric acids, 5-amino-2-hydroxy-4-(4-nitrophenyl)-1,3,2-dioxaphosphorinane 2-oxide and 2-hydroxy-4-(4-methylsulfonylphenyl)-5-phthalimido-1,3,2-dioxaphos phorinane 2-oxide are synthesized in good over yields (64.2%and 72.8%respectively) from 2-amino-1-aryl-1,3-propanediols. The different reaction conditions are necessary in hydrolysis reactions of amino cyclic phosphonyl chlorides.

Atroposelective Synthesis of 2-Arylindoles via Chiral Phosphoric Acid-Catalyzed Direct Amination of Indoles

Indole-based atropisomers are a very important class of axially chiral compounds.However,the atroposelective synthesis of axially chiral 2-arylindole remains largely unexplored.In this study,we report the successful synthesis of atropisomeric 2-arylindoles using direct amination of indoles with p-quinonediimines in the presence of chiral phosphoric acid as a catalyst.Quinonediimine acts as an aminating reagent through formal polarity inversion of imine.The malonate group on the 2-aryl of 2-indoles was found to be essen-tial for high enantioselectivity of the products.This could be due to the additional interaction between the ester group and the cata-lyst,as well as the intramolecular hydrogen bonding.Our findings provide a new strategy for the asymmetric construction of 2-arylindole atropisomers.

Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C_(6)F_(5))_(3)/chiral phosphoric acid

Catalytic enantioselective alkenylation is an efficient method to construct chiral alkene molecules,but the asymmetric alkenylation of simple alkenes catalyzed by metal-free catalysts remains an elusive challenge.Herein,we reported an asymmetric alkenylation of benzoxazinones with diarylethylenes by utilizing a B(C_(6)F_(5))_(3)/chiral phosphoric acid catalyst.A broad of benzoxazinones and diarylethylenes with electron-withdrawing and electron-donating groups were tolerated(up to 95%yield and 97.5:2.5 e.r.)in the methodology under mild reaction conditions.Moreover,the synthetic utility was confirmed by the scaled-up reaction and transformations of the products.The mechanism was preliminarily explored by control reactions,nonlinear effect experiment and DFT calculations.

Quinoxaline-specific enantioselective sulfa-michael reaction catalyzed by chiral phosphoric acid

Highly enantioselective sulfa-Michael additions(SMA)between 2-alkenyl quinoxalines and aromatic thiols are accomplished using a low loading of chiral phosphoric acid catalyst(1 mol%).It was confirmed by an investigation of a lot of azaarenes that the two C-N units of quinoxalines are indispensable for controlling the reaction enantioselectivities.A series of non-terminal 2-alkenes substituted with aryls or alkyls,even other electro-withdrawing groups such as ketones,esters,or amides,selectively reacted and afforded the desired SMA products(48 examples)in good regioselectivities with high yields(up to 99%)and good ee values(up to 97%).

酒石酸衍生的双羟基手性磷酸催化不对称Mannich-type反应

设计合成了数种由天然酒石酸衍生的双羟基手性磷酸,并考察了其对不对称Mannich-type反应的催化性能.结果发现:设计合成的双羟基手性磷酸可以高效催化该反应,并显示中等至良好的对映选择性(高达91%ee).

手性磷酸催化非环状N,N′-缩酮的不对称合成

手性N,N′-缩酮是药物分子和生物活性化合物最重要的核心结构之一,也是有机合成中重要的催化剂或配体。因此,不对称合成N,N′-缩酮具有重要意义。通过手性磷酸、溶剂、催化剂负载量和投料比的筛选,确定了最佳的反应条件:在手性磷酸的催化下,以1,4-二氧六环作为溶剂,5-氨基异噁唑与β,γ-炔基-α-酮亚胺酯在室温下发生区域选择性的氮杂-曼尼希反应,实现异噁唑的不对称N—H烷基化,以中等至良好的收率(46%~83% yield)和较好的对映选择性(82%~92%ee)合成非环状的N,N′-缩酮。所有产物结构由^(1)H NMR,^(13)C NMR和HR-MS(ESI)确证,绝对构型通过X-射线晶体结构分析确定。

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Axially Chiral Compounds

The well-defined conformational properties of axially chiral compounds bring extraordinary values to an assortment of bioactive molecules,advanced materials,organocatalysts as well as chiral ligands in asymmetric transformations.The demonstrated usefulness and untapped potential of axially chiral structural motifs stimulate increasing efforts to develop novel and efficient approaches for their preparation.In this regard,the chiral phosphoric acids broadly used in asymmetric Brønsted acid catalysis have shown high relevance for atroposelective synthesis as well.Our strong interest in reaction chemistry of atropisomers has established a rewarding research programme in our group.The course of studies will be recounted in this account,with discussion focused on the use of chiral phosphoric acids to catalyze construction of several key axially chiral structures such as BINAM,BINOL,NOBIN,arylquinones,SPINOL,arylpyrrole analogues and axially chiral alkenes.

Recent advances in asymmetric reactions catalyzed by chiral phosphoric acids

This review summarizes the very recent advances in asymmetric reactions catalyzed by chiral phosphoric acids（CPAs）, a family of versatile catalysts that catalyze a broad range of reactions to afford diverse chiral molecules. In the past years, different kinds of chiral phosphoric acids have been designed and developed into a privileged class of catalysts in asymmetric synthesis. A number of remarkable achievements have been made by many groups around the world. Due to length limitation, this review only summarizes those works published from January 2016 to November 2017. Meanwhile, catalytic systems which combine metal catalysts and chiral phosphoric acids will not be discussed in this review.

Chiral Spirocyclic Phosphoric Acids and Their Growing Applications

Chiral spirocyclic phosphoric acids(SPAs)are introduced in 2010 and have been versatile catalysts capable of promoting a wide range of asymmetric organocatalytic reactions,such as multi-component reactions,Friedel–Crafts reactions,Pictet–Spengler reactions,Fischer indolizations,cycloaddition reactions,desymmetrization reactions,dearomatization reactions,conjugate addition reactions and rearrangement reactions,etc.Moreover,a diverse range of applications in metal-organic cooperative catalysis,organic photoredox catalysis,total synthesis,materials science and molecular recognition are beautifully illustrated.This account summarizes the past decade's advances in this field and highlights the selected but not comprehensive significant achievements.

Enantioselective three-component Ugi reaction catalyzed by chiral phosphoric acid

A catalytic enantioselective three-component Ugi reaction was developed.SPINOL-derived phosphoric acid with bulky 2,4,6-tricyclohexylphenyl groups at the 6,6′positions was found to be the best catalyst to affordα-amino amide derivatives in good to excellent yields(62%to 99%)and enantiocontrol(81%to>99%enantiomeric excess).This asymmetric reaction was applicable well to an array of aliphatic aldehydes.The gram-scale synthesis,modification of dapsone,and enantioselective synthesis of(R)-Lacosamide underline the general utility of this methodology.Influence of dihedral angles and substituents of the chiral phosphoric acids on the enantioselectivity was also discussed in this article.

An unprecedented synthesis of axially chiral biaryls by rearrangement and aromatization of carbocations with central-to-axial conversion of chirality

The central-to-axial chirality conversion represents a fascinating class of chemical processes consisting of the destruction of stereogenic centers and the simultaneous installation of axial chiral elements,which provides efficient methods for the preparation of axially chiral compounds.However,developing catalytic asymmetric approaches for constructing these central chirality precursors and the efficient central-to-axial chirality conversion remains a challenge due to the requirement of aromatization or elimination process.In this work,we have developed an unprecedented enantioselective intramolecular FriedelCrafts alkylation with unactivated-ketone carbonyls from which a chiral tertiary alcohol was generated with high efficiency and excellent enantioselectivity.In addition,the central-to-axial chirality conversion strategy has been successfully applied to the synthesis of enantioenriched biaryls via a less-explored carbocation-initiated rearrangement and aromatization under the promotion of Lewis acid.This methodology provided a straightforward and sustainable access to a broad range of biaryl-2-carboxylic acid and in excellent yields(up to 92%)and excellent central-to-axial chirality conversion(up to 99%conversion percentage).This work could be a great model for developing new methods for synthesizing axially chiral biaryls and a general protocol for the rearrangement and aromatization of carbocations for further functionalization.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols under different reaction conditions.Using this strategy,two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities(up to 99%yield,95:5 er,>95:5 dr).Moreover,theoretical calculations were performed on the key transition states leading to different stereoisomers,which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions.More importantly,these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity,which demonstrated their potential applications.This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles,but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality.

Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline

Schiff base metal complexes are of great importance in pharmaceutical science owing to their unique chemical properties, which enable them to exhibit diverse biological activities such as anti-bacterial,anti-oxidant, anti-inflammatory, and anti-tumor properties. Furthermore, Schiff base metal complexes can serve as reagents and catalysts in chemical reactions. This review aims to provide an overview of our recently published studies on Cu(Ⅱ) and Pd(Ⅱ) complexes derived from proline Schiff base ligands. We also discuss the potential applications of these metal complexes in the fields of antibacterial and chiral resolution.

手性磷酸催化的有机催化不对称反应

手性磷酸是近年来发展起来的一类新型高效、高对映选择性的Br(?)nsted酸类有机催化剂,已成功应用于催化不对称Mannich反应、还原胺化反应、Pictet-Spengler反应、aza-Diels-Alder反应和aza-Ene反应等许多重要的有机合成反应.手性磷酸催化剂分子内同时含有Lewis碱性位点和Br(?)nsted酸性位点,可同时活化亲电与亲核底物.作为一种新型双功能有机催化剂,手性磷酸具有较高的催化活性和对映选择性,催化剂最低用量可达0.05 mol%.对各类手性磷酸催化剂在有机催化不对称合成反应中的应用研究进展,以及不对称诱导反应的机理、手性磷酸的分子结构及反应条件对其催化活性和不对称诱导活性的影响进行了评述.

手性磷酸催化芳香胺与硝基烯烃的不对称加成反应(英文)

以轴手性联萘酚为原料,合成了一系列手性磷酸催化剂,并首次将其应用于催化芳香胺和硝基烯烃的不对称氮杂迈克尔加成反应中,产物β-硝基胺的产率和对映选择性分别达65%～95%和16%～70%.

BINOL衍生的手性磷酸催化的不对称反应研究进展

综述了近年来BINOL衍生的手性磷酸作为一类强酸性Brφnsted酸催化剂,在不对称氢转移反应、Friedel-Crafts,Mannich,Aza Diels-Alder,Aza-ene-type,Pictet-Spengler等反应中的研究进展。参考文献37篇。

(R)-BINOL制备的手性磷酸在不对称Mannich反应中的应用

手性磷酸是本世纪初发展起来的一种新型有机小分子催化剂,其拥有一个Brnsted酸酸性位点和一个Lewis碱碱性位点,由于其酸性位点适宜的酸性,可向一些反应分子提供质子或与其形成氢键的弱相互作用,而碱性位点的磷氧双键可以提供孤对电子,因此手性磷酸具有双功能催化剂的优点,促使其在有机不对称反应中显示出独特的催化活性以及较高的对映选择性,特别在催化亚胺的反应中,更显示出特别高的催化效能。针对手性磷酸在不对称Mannich反应中的应用进展及其不对称催化作用机理进行综述,并对该类应用未来的发展方向做了一定的预测与展望。

BINOL衍生手性磷酸在傅克反应中的应用进展

由联二萘酚(BINOL)衍生的手性磷酸是近年来出现的催化性能优异的Brφnsted酸催化剂,其在不对称傅克反应中的应用是当前的研究热点之一。本文综述了BINOL衍生的手性磷酸作用下,富电子芳烃与底物亚胺及烯胺间不对称傅克反应的研究进展。

手性BINOL磷酸催化剂在不对称转化中的应用

3,3'-位基团取代手性BINOL磷酸在不对称催化反应中具有较强的催化活性。其原因在于:(1)手性BINOL磷酸具有较强的(P=O)Lewis碱和较强的(P-OH)Lewis酸,可以有效通过与催化底物之间形成氢键,激活反应体系;(2)在手性BINOL磷酸的3,3'-位上引入阻位基团,建立有效的手性环境,可以成功地诱导不对称转化。本文例举了通过氢键相互作用,手性BINOL磷酸催化剂成功地诱导不对称催化反应。