Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes

Divinyl ketones bearing alpha-ester or alpha-amide groups undergo Nazarov cyclizations to give cylopentenones using copper-bisoxazoline Lewis acid complexes with moderate to good ees. [reaction: see text]     

Enantioselective total synthesis of eicosanoid and its congener, using organocatalytic cyclopropanation, and catalytic asymmetric transfer hydrogenation reactions as key steps

An enantioselective unified strategy for the syntheses of the oxylipin class of natural products was accomplished. Our strategy relies on three catalytic steps: (a) organocatalytic cyclopropanation, (b) the catalytic asymmetric transfer hydrogenation (CATHy) reaction, and (c) the Nozaki-Hiyama-Kishi reaction.     

Development of atom-economical catalytic asymmetric reactions under proton transfer conditions: construction of tetrasubstituted stereogenic centers and their application to therapeutics

The development of atom-economical catalytic asymmetric reactions based on two distinct sets of catalyst, a rare earth metal/amide-based ligand catalyst and a soft Lewis acid/hard Br?nsted base catalyst, is reviewed. These catalytic systems exhibit high catalytic activity and stereoselectivity by harnessing a cooperative catalysis through hydrogen bond/metal coordination and soft-soft interactions/hard-hard interactions, respectively. The effectiveness of these cooperative catalysts is clearly delineated by the high stereoselectivity in reactions with highly coordinative substrates, and the specific activation of otherwise low-reactive pronucleophiles under proton transfer conditions. The rare earth metal/amide-based ligand catalyst was successfully applied to catalytic asymmetric aminations, nitroaldol (Henry) reactions, Mannich-type reactions, and conjugate addition reactions, generating stereogenic tetrasubstituted centers. Catalytic asymmetric amination and anti-selective catalytic asymmetric nitroaldol reactions were successfully applied to the efficient enantioselective synthesis of therapeutic candidates, such as AS-3201 and the β(3)-adrenoreceptor agonist, showcasing the practical utility of the present protocols. The soft Lewis acid/hard Br?nsted base cooperative catalyst was specifically developed for the chemoselective activation of soft Lewis basic allylic cyanides and thioamides, which are otherwise low-reactive pronucleophiles. The cooperative action of the catalyst allowed for efficient catalytic generation of active carbon nucleophiles in situ, which were integrated into subsequent enantioselective additions to carbonyl-type electrophiles.     

Direct catalytic asymmetric anti-selective Mannich-type reactions

The simple chiral pyrrolidine catalyzed asymmetric anti-selective Mannich-type reaction is presented; the reaction gives the corresponding amino acid derivatives with 10:1- >19:1 dr and 97-99% ee.     

Direct catalytic asymmetric aldol reactions of aldehydes

The development of a direct catalytic enantioselective aldol reaction of aldehydes with activated carbonyl compounds catalyzed by chiral amines is presented and the potential demonstrated by the synthesis of optically active beta-hydroxycarboxylic acid derivatives.     

Recent advances towards catalytic asymmetric Conia-ene-type reactions

Conia-ene reactions,as a type of ene reactions,have not become a remarkable focus until the beginning of21~(st) century,when Lewis acids served as powerful catalysts and found an increasingly broad utilization in this field.Consequently,the catalytic Conia-ene reactions have gained great significance in synthetic chemistry due to their high efficiency and atom economy on the construction of valuable cyclic molecules.During the past two decades,the rapid development of transition-metal catalysis and organocatalysis has imposed a profound impact on the exploration of asymmetric Conia-ene reactions.As a result,several strategies have been developed and applied successfully.Organized on the basis of the catalytic system,this review comprehensively presents a summary of recent progress achieved in this emerging domain,aimed at highlighting the reactions' features,practicalities,and the mechanistic rationale is presented where possible.     

Enantioselective synthesis of cyclic enol ethers and all-carbon quaternary stereogenic centers through catalytic asymmetric ring-closing metathesis

The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru catalysts (those that do not bear a phosphine ligand) promote ARCM in some cases, such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give rise to efficient ARCM and deliver the desired products in the optically enriched form. Thus, Mo-catalyzed enantioselective transformations allow access to various five- and six-membered cyclic enol ethers in up to 94% ee from readily available achiral starting materials. The first examples of catalytic ARCM that lead to the formation of all-carbon quaternary stereogenic centers are also disclosed. Mechanistic models that offer a plausible rationale for the identity of major enantiomers as well as the observed levels of enantioselectivity are provided. Representative examples demonstrate that the enol ether moiety and the unreacted alkene of the ARCM products can be discriminated with excellent site selectivity (>98%).     

Application of beta-hydroxysulfoximines in catalytic asymmetric phenyl transfer reactions for the synthesis of diarylmethanols

Enantiomerically enriched diarylmethanols have been prepared by catalyzed asymmetric phenyl transfer reactions onto aromatic aldehydes with use of readily available beta-hydroxysulfoximines as catalysts. As the aryl source, combinations of diethylzinc with either diphenylzinc or triphenylborane have been applied affording arylphenylmethanols with up to 93% ee in good yields. Various functionalized aldehydes and heterocyclic substrates are tolerated, yielding synthetically relevant products.     

Enantioselective synthesis of biologically important spiro[indoline-3,2′-quinazolines] via catalytic asymmetric isatin-involved tandem reactions

The enantioselective synthesis of biologically important spiro[indoline-3,2′-quinazoline] scaffolds with a quaternary stereogenic center with fair to excellent enantioselectivities (up to 95% ee) has been established via an isatin-involved asymmetric catalytic tandem condensation/amide addition with 2-aminobenzamides. In addition, we also report on the enantioselective synthesis of various substituted spiro[indoline-3,2′-quinazolines], which will cast light on the preparation of chiral spiro-architectures with concomitant creation of quaternary stereogenic centers.     

The catalytic asymmetric Mannich-type reactions in aqueous media

The catalytic, diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF(2), a chiral diamine ligand, and trifluoromethanesulfonic acid.     

Recent progress on direct catalytic asymmetric vinylogous reactions

Direct catalytic asymmetric vinylogous reaction serves as a powerful tool to introduce stereocenter(s) at the γ- or/and even more remote position(s) of the vinylogous products in an atom-economical and efficient way. A variety of direct catalytic asymmetric vinylogous reactions with broad substrate scope and mild reaction conditions has been developed. Both metal catalysis and organocatalysis contributed in this field and led to the vinylogous products in high stereoselectivity. These vinylogous reactions provided efficient pathways for the synthesis of highly functionalized optically pure compounds, especially these with potential biological activity and pharmacological activity. This digest paper mainly focuses on the most recent developments in this field, including both nucleophilic addition and nucleophilic substitution.