亚胺及其类似物的催化不对称炔基化反应新进展

手性炔丙胺是天然产物和药物活性分子不对称全合成中常用的关键中间体,亚胺及其类似物的不对称炔基化反应可以为该砌块提供高效高对映选择性的合成路径;此外通过合理的底物和反应设计,亚胺的不对称炔基化反应还能作为一系列串联反应的起点,来合成多种结构新颖的含氮杂环化合物.因此,亚胺及其类似物的高效高对映选择性炔基化反应得到合成化学...     

Systematic construction of a monotetrahydrofuran-ring library in annonaceous acetogenins by asymmetric alkynylation and stereodivergent tetrahydrofuran-ring formation

All eight diastereoisomers of the monotetrahydrofuran-ring cores of annonaceous acetogenins have been synthesized through utilization of asymmetric alkynylation and stereodivergent one-pot tetrahydrofuran-ring formation. In all cases, the asymmetric alkynylation proceeded with very high diastereoselectivity to give eight kinds of optically pure tetrahydrofuran core from a common alpha-oxyaldehyde. We also describe a comparison of the (1)H NMR, (13)C NMR, and CD spectral data of the eight isomers and give full details of the tetrahydrofuran-ring construction including a model study of asymmetric alkynylation.     

Enantioselective alkynylation of aromatic aldehydes catalyzed by new chiral amino alcohol-based ligands

A series of binaphthyl-derived amino alcohols were synthesized and used as catalytic ligands in the asymmetric alkynylation of aromatic aldehydes in the presence of a dialkylzinc reagent. The alkynylation of a variety of aromatic aldehydes gave the corresponding chiral propargylic alcohols in 61–93% e.e.     

Enantioselective synthesis of a GPR40 agonist AMG 837 via catalytic asymmetric conjugate addition of terminal alkyne to α,β-unsaturated thioamide

A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by a soft Lewis acid/hard Br?nsted base cooperative catalyst, allowing efficient construction of the requisite stereogenic center. The thioamide functional group is key to both activation in asymmetric alkynylation and facile transformation into carboxylic acid.     

Systematic synthesis of Bis-THF ring cores in annonaceous acetogenins

Systematic synthesis of bis-THF ring cores, synthetic intermediates of adjacent bis-THF annonaceous acetogenins, has been achieved by asymmetric alkynylation and subsequent stereodivergent THF ring formation. The asymmetric alkynylation of alpha-tetrahydrofuranic aldehyde with (S)-3-butyne-1,2-diol derivatives gave good yields of erythro- and threo-adducts with very high diastereoselectivity. These adducts were converted into four types of bis-THF cores via two kinds of one-pot THF ring formation. [reaction: see text]     

Total synthesis of murisolins and evaluation of tumor-growth inhibitory activity

Convergent total syntheses of murisolin (1), natural 16,19-cis-murisolin 2, and unnatural 16,19-cis-murisolin 3 were accomplished by asymmetric alkynylation of alpha-tetrahydrofuranic aldehyde with a diyne and Sonogashira coupling with a gamma-lactone segment as the key steps. Stereoisomers of alpha-tetrahydrofuranic aldehyde were synthesized with high optical purity and the asymmetric alkynylation of these with 1,6-heptadiyne proceeded in good yield and with high diastereoselectivity. The cell-growth inhibition profile and COMPARE analysis of the synthetic compounds 1-3 were also investigated.     

Stereodivergent and reiterative synthesis of bistetrahydrofuran ring cores of annonaceous acetogenins

Eight diastereoisomers of the bistetrahydrofuran ring cores of annonaceous acetogenins have been synthesized by asymmetric alkynylation of alpha-tetrahydrofuranic aldehydes and stereodivergent one-pot tetrahydrofuran (THF) ring formation. In all cases, the asymmetric alkynylation proceeded with very high diastereoselectivity to give eight kinds of optically pure THF cores. We also describe a comparison of the (1)H and (13)C NMR spectral data of the eight isomers and give full details of the THF ring construction.     

Highly stereoselective and stereodivergent synthesis of four types of THF cores in acetogenins using a C4-chiral building block

[reaction: see text] Four stereoisomers of the THF cores, synthetic intermediates of acetogenins, have been synthesized with high diastereoselectivity by asymmetric alkynylation and subsequent stereodivergent THF ring formation. The asymmetric alkynylation of alpha-oxyaldehyde with (S)-3-butyne-1,2-diol derivatives (C4-unit) gave good yields of syn and anti adducts with >97:3 dr and 94:6 dr, respectively. These adducts were converted into the four types of THF compounds via one-pot THF formation or via intramolecular Williamson synthesis.     

Asymmetric syntheses of a GPR40 receptor agonist via diastereoselective and enantioselective conjugate alkynylation

Two asymmetric methods to synthesize a potent GPR40 receptor agonist are reported. Both synthetic routes utilize readily available, inexpensive starting materials and reagents. The first route relies on a highly diastereoselective conjugate alkynylation of an ephedrine-derived oxazepanedione acceptor. The second route features the enantioselective alkynylation of a Meldrum’s acid-derived acceptor mediated by a chiral zinc cinchonidine reagent.     

InBr3-catalyzed direct alkynylation of nitrones with terminal alkynes: an efficient synthesis of N-hydroxy-propargyl amines

An InBr₃-catalyzed direct and efficient alkynylation of nitrones with terminal alkynes was developed. The process enables practical synthesis of a wide range of synthetically useful N-hydroxy-propargyl amine derivatives in good yields under mild conditions. The application of this method to optically active propargylic N-hydroxyamines syntheses was also described. With chiral nitrones, good diastereoselectivities were obtained. Moreover, the first chiral indium(III) complex-catalyzed asymmetric alkynylation of nitrone was achieved with moderate enantioselectivity.     

Catalytic enantioselective synthesis of adociacetylene B

A catalytic enantioselective total synthesis of adociacetylene B (2) in five steps is reported. The efficiency of this synthesis was enabled by an asymmetric zinc alkynylation catalyzed by the proline-derived ligand (1).     

Asymmetric catalytic synthesis of the proposed structure of trocheliophorolide B

A concise catalytic asymmetric synthesis of the proposed structure of trocheliophorolide B is reported. The synthetic sequence notably features an asymmetric acetaldehyde alkynylation, a Ru-catalyzed alder-ene reaction, and a Zn-ProPhenol ynone aldol condensation. Comparison with the reported data suggests a misassignment of the natural product structure.     

Asymmetric synthesis of (+)-chloriolide

An asymmetric synthesis of 12-membered ring macrolide, chloriolide has been accomplished by adopting a linear strategy. Lipase-catalyzed enzymatic kinetic resolution (EKR), asymmetric alkynylation using Trost pro-phenol catalyst followed by Yamaguchi macrolactonization has been successfully employed to achieve the target molecule.     

Catalytic enantioselective alkynylation of prochiral sp3 C-H bonds adjacent to a nitrogen atom

[reaction: see text] The construction of chiral carbon centers via the first catalytic asymmetric alkynylation of prochiral CH2 groups was developed by using a copper-catalyzed double activation of sp3 and sp C-H bonds. Optically active 1-alkynylated tetrahydroisoquinolines were obtained by this method.     

Synthesis of C3-symmetric tris(beta-hydroxy amide) ligands and their Ti(IV) complex-catalyzed enantioselective alkynylation of aldehydes

[reaction: see text]. A series of new chiral C3-symmetric tris(beta-hydroxy amide) ligands have been synthesized via the reaction of 1,3,5-benzenetricarboxylic chloride and optically pure amino alcohols (up to 96% yield). The asymmetric catalytic alkynylation of aldehydes with these new C3-symmetric chiral tris(beta-hydroxy amide) ligands and Ti (O(i)'Pr)4 was investigated. Ligand 4c synthesized from (1R,2S)-(-)-2-amino-1,2-diphenylethanol is effective for the enantioselective alkynylation of various aldehydes, and high enantioselectivity was obtained with aromatic aldehydes and alpha,beta-unsaturated aldehyde (up to 92% ee).     

Asymmetric alkynylation of aldehydes with propiolates without high reagent loading and any additives

The asymmetric alkynylation of aliphatic and aromatic aldehydes with propiolates was mediated by dialkylzinc and a novel prolinol catalyst without high reagent loading and any additives, such as Ti(Oi-Pr)(4), to give the corresponding γ-hydroxy-α,β-acetylenic esters with high enantiomeric excess of up to 95%.     

Bisoxazolidine-catalyzed enantioselective alkynylation of aldehydes

A C2-symmetric bisoxazolidine derived from aminoindanol has been successfully applied in the asymmetric alkynylation of aldehydes. The ligand is readily available, has a wide substrate scope, and catalyzes the formation of chiral propargylic alcohols with excellent yields and enantioselectivties.     

双功能金属锌(Salen)配合物催化的醛的不对称炔基加成反应

本文研究了双功能金属锌(Salen)配合物催化的醛的不对称炔基加成反应。在相应的反应中,当手性salen配体的C3和C3’位有路易斯碱性的1-哌啶甲基取代时,其和金属锌形成的配合物较一般的锌(Salen)配合物具有更好的催化活性和立体选择性。     

Catalytic asymmetric syntheses of (−)-oudemanisin A and its diastereomer

The first asymmetric catalytic synthesis of (?)-oudemanisin A 1a and its diastereomer 1b has been achieved. The key steps of our strategy involved the asymmetric alkynylation of an unsaturated aliphatic aldehyde catalyzed by Trost’s ProPhenol ligand, chemoselective oxidation of the olefinic diol, base-induced ring opening of the lactone, and acylation–alkylation of the ester.