Nucleophilic substitution at phosphorus: stereochemistry and mechanisms

This review is devoted to the stereochemistry of nucleophilic substitution reactions at phosphorus. The study of the reactions of phosphoryl group transfer is important for biological and molecular chemistry. The stereochemistry and mechanisms of S_N1(P) monomolecular and S_N2(P) bimolecular nucleophilic substitution reactions of organophosphorus compounds are discussed. It has been shown that hydrolysis of many natural phosphates proceeds according to the monomolecular S_N1(P) mechanism via the formation of metaphosphate intermediate (PO₃^?). S_N2(P) nucleophilic substitution at chiral trivalent or pentavalent phosphorus compounds proceeds via the formation of penta-coordinated transition state or pentacoordinate intermediate.     

Oxidation-Reduction Condensation a New Method for Peptide Synthesis

Organic trivalent phosphorous compounds such as trialkyl phosphites and trialkyl or triarylphosphines are well known to be powerful deoxygenation reagents and have been used in various reduction reactions. But, it is rather a new aspect to make use of their property of deoxygenation for the gsneration of active acyl groups. Since the discovery of the rezcticn of mercuric acetate with trivalent phosphorous coqounds to yield acetic anhydride, our attention has been fccused on the generation of acyl groups and several novel reactions have been found which are applicable to the preparation of acid anhydride and peptide linkages. In considering these reactions described herein, it is necessary to choose appropriate oxidation reagents together with reducing reagents (trivalent phosphcrous compounds) because these dehydration reactions essentially proceed via an oxiaation reduction process as depicted in the following scheme.     

聚合物支载噁唑类化合物在不对称反应中的应用

聚合物支载噁唑类化合物主要包括聚合物支载噁唑烷酮、噁唑啉和硼杂噁唑啉等,其在不对称反应中主要用作手性助剂、手性催化剂及催化剂配体.由于其便于分离提纯、可以回收重复使用且立体选择性没有明显降低等优点在不对称反应中得到了广泛的应用.综述了近年来聚合物支载的噁唑类化合物在不对称反应中的应用     

聚合物支载噁唑类化合物在不对称反应中的应用

聚合物支载噁唑类化合物主要包括聚合物支载噁唑烷酮﹑噁唑啉和硼杂噁唑啉等, 其在不对称反应中主要用作手性助剂﹑手性催化剂及催化剂配体. 由于其便于分离提纯﹑可以回收重复使用且立体选择性没有明显降低等优点在不对称反应中得到了广泛的应用. 综述了近年来聚合物支载的噁唑类化合物在不对称反应中的应用.     

Stereolabile chiral compounds: analysis by dynamic chromatography and stopped-flow methods

Enantiomerization and diastereomerization reactions of chiral compounds play a major role in all aspects of chemistry spanning a wide bridge from drug development to supramolecular chemistry. Traditionally, these reactions are studied by variable-temperature NMR spectroscopy and chiroptical methods such as polarimetry. However, powerful complimentary methods based on chromatography and electrophoresis have been developed and applied to a variety of stereolabile chiral compounds. This tutorial review explains the principles, applications, and limitations of dynamic chromatography and chromatographic and electrophoretic stopped-flow analysis for the investigation of isomerization reactions of chiral compounds.     

Recent Advances in Asymmetric Catalysis Using p-Block Elements

The development of new methods for enantioselective reactions that generate stereogenic centres within molecules are a cornerstone of organic synthesis. Typically, metal catalysts bearing chiral ligands as well as chiral organocatalysts have been employed for the enantioselective synthesis of organic compounds. In this review, we highlight the recent advances in main group catalysis for enantioselective reactions using the p-block elements (boron, aluminium, phosphorus, bismuth) as a complementary and sustainable approach to generate chiral molecules. Several of these catalysts benefit in terms of high abundance, low toxicity, high selectivity, and excellent reactivity. This minireview summarises the utilisation of chiral p-block element catalysts for asymmetric reactions to generate value-added compounds.     

Transition metal-catalyzed asymmetric reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs

This review describes the development of a new class of chiral phosphorus ligands: amino acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation with cyclic beta-keto esters as prochiral nucleophiles was initially examined using P-chirogenic diaminophosphine oxide 1a, resulting in highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 13, which functions as the actual ligand. Pd-catalyzed asymmetric allylic substitutions of both acyclic and cyclic substrates were also examined using various nucleophiles such as malonate derivatives, nitromethane, aliphatic amines, and aromatic amines, providing a variety of chiral compounds with good to excellent enantioselectivity. In addition, Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were examined using structurally optimized P-chirogenic diaminophosphine oxides, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed catalytic asymmetric process was successfully applied to the catalytic enantioselective synthesis of biologically active compounds, (R)-preclamol, (R)-baclofen hydrochloride, and (-)-paroxetine.     

Imide-amide rearrangement of oxazaphosphorimidates: studies towards the application to the synthesis of chiral Lewis bases

The Lewis acid catalysed imide-amide rearrangement of oxazaphosphorimides to diazaphoshoramides is reported for the first time. In spite of the similarity to the previously reported Lewis acid catalysed imide-amide rearrangement of dioxaphosphorimides to oxazaphosphoramides we show that this rearrangement proceeds by a different mechanism, not involving the formation of an oligomeric intermediate. The oxazaphosphorimides are prepared in situ by the Staudinger reaction of the appropriate trivalent phosphorus compound with an azide and after the addition of BF₃·OEt₂, undergo rearrangement to the corresponding diazaphosphoramides. We have found that the rearrangement occurs with retention of configuration at the phosphorus atom and inversion of configuration at the rearranged carbon atom. When starting from chiral 1,2-aminoalcohol, substituted at the carbon atom that undergoes rearrangement, a mixture of diastereomers is obtained, but the diastereomeric ratio, initially obtained in the formation of the trivalent phosphorus compounds is maintained during the whole transformation. This implies that if the rearrangement is to be used for the preparation of chiral phosphoramides with defined stereochemistry at the phosphorus atom, a high diastereoselectivity during the preparation of the trivalent phosphorus precursors should be obtained.     

手性炔丙醇的不对称催化合成研究进展

手性炔丙醇是一种重要中间体化合物,作为合成多种光学活性化合物的重要合成前体受到学者们广泛关注。目前通过酮的不对称催化反应合成手性炔丙醇的研究开发具有极大发展前景,因此本文围绕酮类化合物的不对称催化反应来进行综述,结合相关反应最新研究进展,全面总结并分类了不对称催化还原、催化不对称加成等反应类型,介绍了合成不同结构手性炔丙醇的新思路,并对酮的不对称催化反应在未来能成为工业化重要生产途径作出展望。     

Phosphine-mediated enantioselective synthesis of carbocycles and heterocycles

Nucleophilic chiral phosphine catalysis has been prosperous in asymmetric synthesis over the past two decades. Various tunable chiral phosphines display excellent activity and selectivity in asymmetric transformations including acycloaddition reactions and cycloaddition reactions. Enantiomerically enriched cyclic compounds are ubiquitous in natural products and drug molecules. These phosphinecatalyzed reactions provide effective and extensive strategies for the synthesis of a series of complex cyclic compounds as well as the synthesis of chiral compounds which could be easily transformed to carbocycles and heterocycles. This minireview summarizes recent developments in this area and highlights meaningful breakthroughs.     

Chiral pool based synthesis of pyrrolidinium ionic liquids

Chiral ionic liquids show promising applications in various different fields. A series of pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was prepared in good yields using an efficient, economic and simple pathway. The chirality was introduced using (l)-lactate and (l)-menthol derivatives. The resultant chiral compounds were characterized by both spectroscopy and polarimetry. We envision that these new chiral compounds can serve as effective reaction media and chiral catalysts for asymmetric reactions, which are presently being investigated in our lab.     

三价碘试剂促进的氧化反应研究进展

三价碘试剂的反应性能类似于过渡金属如汞、钛和铅,并且具有环境友好、价值低廉、反应条件温和、反应后处理简单和商业可利用的特点,因此在有机合成中得到广泛应用,特别是作为一种高效的选择性氧化试剂,受到广大有机化学工作者的亲睐。本文就三价碘试剂促进的氧化反应,从醇的氧化、羰基化合物的氧化官能团化到氧化硒化和铋化等14类反应进行了简单的综述。     

Catalytic Asymmetric Hetero-Diels-Alder Reactions of Carbonyl Compounds and Imines

Asymmetric catalysis is a challenge for chemists: How can we design catalysts to achieve the goal of forming optically active compounds? This review provides the reader with an overview of the development of catalytic asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines. Since its discovery, the Diels-Alder reaction has undergone intensive development and is of fundamental importance for synthetic, physical, and theoretical chemists. The Diels-Alder reaction has been through different stages of development, and at the beginning of the 21st century catalytic Diels-Alder reactions are one of the main areas of focus. The preparation of numerous compounds of importance for our society is based on cycloaddition reactions to carbonyl compounds and imines. There are several parallels between the reactions of carbonyl compounds and those of imines, which, however, begin to vanish on entering the field of catalytic reactions. Why? From a mechanistic point of view some similarities can be drawn, but the synthetic development of catalytic enantioselective hetero-Diels-Alder reactions of imines are several years behind those of the carbonyl compounds. For hetero-Diels-Alder reactions of carbonyl compounds there a number of different chiral catalysts, and great progress has been achieved in developing enantioselective reactions for unactivated and activated carbonyl compounds. In contrast the development of catalytic enantioselective hetero-Diels-Alder reactions of imines is in its infancy and only few catalytic reactions have been published. This review will focus on the most important developments, and discuss the synthetic and mechanistic aspects of enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral Lewis acids. For the hetero-Diels-Alder reactions of imines, the diastereoselective reactions of optically substrates catalyzed by Lewis acids will be presented first, followed by the catalytic enantioselective reactions.     

手性salen(Mn)催化烯烃不对称环氧化反应的研究进展

烯烃的不对称环氧化物通过选择性开环或者官能团的转化,可以生成一系列有价值的手性化合物,被广泛用作医药、农药、香料等精细化学品的合成中间体.手性Mn(salen)金属配合物被证明是烯烃不对称环氧化最有效的催化剂之一.本文综述了近年来均相手性Mn(salen)催化剂、有机聚合物固载的手性Mn(salen)、无机载体固载手性...     

Pd-catalyzed asymmetric allylic substitution reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs

This paper describes the development of a new class of chiral phosphorus ligand: aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 1a, resulting in the highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 12, which functions as the actual ligand. Furthermore, asymmetric allylic amination was examined using Pd-DIAPHOX catalyst systems, providing a variety of chiral allylic amines.     

Fluorinated Imines in Tandem and Cycloaddition Reactions

The chemistry of fluorinated compounds has experienced extraordinary growth in recent decades due to the many and varied properties which many of the compounds that contain fluorinated groups possess. Among all of them, fluorinated chiral imines, in particular the Ellman's imines, are of great importance since they are some of the most interesting building blocks for the synthesis of a large number of enantioenriched carbocycles and heterocycles with extraordinary biological and synthetic properties. This personal account covers the most significant results obtained in our research group in the last two decades concerning asymmetric tandem reactions, paying special attention to the intramolecular aza-Michael reaction (IMAMR), diversity oriented synthesis (DOS), asymmetric tandem reactions involving a p-tolylsulfinyl group as chiral inducer and cycloaddition processes, in particular, the Pauson-Khand reaction, [2+2+2]-cycloadditions and metathesis reactions, starting mainly from enyne compounds and through the use of fluorinated chiral N-sulfinyl imines and their derivatives as starting materials.     

Synthesis and structure of 1-(1,3,2-dioxaphospholan-2-yl)- and 1-(4-methyl-1,3,2-dioxaphosphinan-2-yl)azepan-2-one copper diacetate complexes

Complexation of trivalent phosphorus amides with copper acetate leads to compounds possessing catalytic activity in oligomerization reactions [1].     

Reactions of alicyclic epoxy compounds with oxygen-centered nucleophiles

The review analyzes the reactions of alicyclic epoxy compounds with oxygen-containing nucleophiles (alcohols, water, and organic acids), describes biologically active products of these reactions, and discusses their mechanisms and results of their simulation by quantum-chemical methods. The regio-and stereoselectivity of nucleophilic reactions of epoxy compounds and the activation of epoxy ring by achiral and chiral catalysts are also considered.     

Organocatalytic Synthesis of Chiral Halogenated Compounds

This account summarizes our recent efforts in the enantioselective organocatalytic synthesis of chiral halogenated compounds. The enantioselective α-halogenation of aldehydes, decarboxylative chlorination of β-keto acids, and enantioselective C−C bond formation at the trifluoromethylated prochiral carbon to yield the corresponding organohalides with chlorinated, fluorinated, or trifluoromethylated chiral stereogenic centers are discussed. We applied common organocatalysts, such as Jørgensen-Hayashi catalyst and cinchona alkaloid-derivatived catalyst, and developed novel chiral amine catalysts for these reactions. This account also discusses stereospecific derivatizations of the resulting chiral halogenated compounds via nucleophilic substitution. Thus, we synthesized many novel chiral compounds that have not been reported, even as racemates.     

Chiral Cinchona Alkaloid‐Thiourea Catalyzed Mannich Reaction for Enantioselective Synthesis of β‐Amino Ketones Bearing Benzothiazol Moiety

Mannich reactions of imine with acetylacetone were effectively catalyzed by the modified chiral cinchona alkaloid‐derived thiourea. The reactions led to chiral β‐amino carbonyl compounds in high yields and good enantioselectivities. The study demonstrated for the first time that Mannich reactions of unmodified acetylacetone with heterocyclic imine derived from benzothiazole can be promoted by chiral bifunctional organocatalyst.