铜络合物催化的格氏试剂不对称1,4-共轭加成反应研究进展

铜络合物催化的有机金属试剂与α,β-不饱和羰基化合物的1,4-共轭加成反应, 是形成新的C—C键的重要方法之一. 介绍了铜络合物催化的格氏试剂与α,β-不饱和羰基化合物的立体选择性1,4-共轭加成反应的研究进展.     

铜催化格氏试剂不对称共轭加成研究进展

铜催化格氏试剂不对称1,4-、1,6-及1,2-共轭加成是构建手性碳的重要方法,其加成产物是许多天然产物以及手性药物合成的关键中间体.对铜催化的格氏试剂不对称1,4-、1,6-及1,2-共轭加成反应进行了较全面的综述,其中涉及的受体种类包括α,β-不饱和酮、不饱和酯、不饱和内酯、不饱和硫酯、不饱和醛和不饱和砜.此外,对不对称1,4-共轭加成反应的机理研究也进行了较详细的介绍.     

光学活性脯氨酸催化的不对称有机合成反应

总结了D-或L-脯氨酸作为光学活性有机分子催化剂催化的涉及C＝O, N＝N, C＝N或N＝O键不对称Aldol型反应和α,β-不饱和烯酮及硝基烯烃的不对称共轭加成反应.     

3,6-二氯哒嗪-金鸡纳生物碱衍生物催化不对称“中断的”Feist-Bénary反应的研究

将3,6-二氯哒嗪-金鸡纳生物碱衍生物用于催化β-二羰基化合物与溴乙酰甲酸乙酯/β-取代的溴乙酰甲酸乙酯的不对称“中断的”Feist-Bénary反应, 得到了较高的化学产率(72%～97%)和最高达93% ee的立体选择性.     

手性烯烃-金属配合物的合成及在不对称催化方面的应用

烯烃的双键可以与金属钌、铑、钯、铂、镍等发生配位形成配合物。目前,已有大量的手性双烯烃-金属配合物、手性有机膦烯烃-金属配合物、手性有机胺烯烃-金属配合物被合成出来。烯烃-金属配合物被广泛用于催化不对称1,4-加成反应中,并取得了较好的产率和ee值。另外,烯烃-金属配合物也被用于催化不对称[4+2]环加成反应及其他关环反应。     

不对称催化Pictet-Spengler反应研究进展

手性四氢-β-咔啉骨架广泛存在于天然产物和药物分子中, 是其活性的关键结构. 不对称Pictet-Spengler反应是高效构建四氢-β-咔啉化合物的直接途径. 根据有机催化剂种类, 我们从手性磷酸、 手性方酰胺和其他催化剂3个方面, 综述了近5年来有机催化不对称Pictet-Spengler反应的研究进展.     

轴向手性膦氮配体及其在不对称催化合成中的应用

本文较为详细地综述了轴向手性膦氮配体合成及其在不对称烯丙基取代反应、不对称1,4－共轭加成反应及不对称硼氢化反应中的应用。     

L-脯氨酸对离子液体介质中的不对称Michael反应催化性能研究

研究了L-脯氨酸对离子液体介质中醛(酮)与β-硝基烯烃的不对称Michael加成反应的催化性能, 利用X射线单晶衍射对Michael产物结构进行了表征. 结果表明, 反应在遵循胺催化机理的同时, 烯胺是从Re面对β-硝基烯烃进行加成, 产物的优势结构为(1R,2S)的syn型. 脯氨酸在离子液体1-正己基-3-甲基咪唑氯盐中显示良好的催化性能, 室温反应3～5 h, 得到89%以上收率的Michael产物, 其ee值最高70%. 脯氨酸与离子液体形成的催化体系具有良好的重复使用性能, 可至少稳定地重复使用6次.     

Lewis酸催化下2-(2,3,5-三-O-苯甲酰基-D-呋喃核糖)-1,4-氢醌的合成

在不同Lewis酸催化下, 使用1,4-二苯酚和1-O-乙酰基-2,3,5-三-O-β-D-呋喃核糖进行反应, 以较高产率合成了α和β型芳香呋喃糖苷, 并利用¹H-¹H NOESY谱对2-(2,3,5-三-O-苯甲酰基-D-呋喃核糖)-1,4-氢醌(5)的立体构型进行了表征. 应用无水AlCl₃, ZnCl₂和BF₃•Et₂O等Lewis酸催化剂仅得到β型氧糖苷3, 应用TiCl₄得到β型氧糖苷3以及α和β型碳糖苷的混合物5, 而应用SnCl₄则得到α和β型碳糖苷5.     

铜催化有机锌试剂对烯酮的不对称共轭加成反应研究新进展

形成C-C键的反应是有机合成领域研究热点[1~3].α,β-不饱和体系的加成反应是形成C-C键的重要方法[4].而1,4-共轭加成反应[5~7]最引人们注意(如图式1所示),不对称的1,4-共轭加图式1铜催化有机锌试剂对烯酮的不对称共轭加成反应Schem e 1 Copper catalyzed asymm etric con juga     

First asymmetric synthesis of 3-alkoxycarbonyl-2-amino-4-aryl-4H-naphtho[1,2-b]pyrans

The first asymmetric synthesis of 3-alkoxycarbonyl-2-amino-4-aryl-4H-naphtho[1,2-b]pyrans, by Michael addition of 1-naphthol to chirally modified arylidenecyanoacetates 6 and 7 , is described. Good yields and low diastereomeric excesses have been obtained in the 1,4-conjugate additions. The absolute stereochemistry at C-4 in major isomers of pyrans 8 and 9 has been assigned as 5 by X-ray analysis of major pyran 8 .     

An enantioselective catalytic approach to syn deoxypropionate units combining asymmetric Cu-catalyzed 1,6- and 1,4-conjugate addition

A novel iterative approach to the synthesis of the naturally ubiquitous syn deoxypropionate motif is reported. The route comprises a new Horner–Wadsworth–Emmons reagent to prepare α,β,γ,δ-bisunsaturated thioesters. Next, two Me-substituents are introduced in high yield, regio- and enantioselectivity using sequential asymmetric Cu-catalyzed 1,6-conjugate addition, base-catalyzed olefin isomerization and Cu-catalyzed enantioselective 1,4-conjugate addition. After reduction to the aldehyde these transformations can be repeated to install three or more Me groups with a syn 1,3-relationship.     

Advances on asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media

Asymmetric Michael addition reactions or 1,4-conjugate addition reactions are considered to be the fundamental C–C bond-forming reaction for the construction of chiral β-nitro, β-carbonyl and several other important structural motifs in organic synthesis. After the development of many chiral metal complexes as catalysts, a tremendous growth in the design and applications of variety of new chiral organocatalysts for asymmetric 1,4-conjugate addition reactions has been witnessed over the last two decades. Initially, asymmetric organocatalysis has been performed in organic solvents, but gradually performing the same catalysis in aqueous and semi-aqueous media became a necessity due to environmental aspects as well as to achieve better reactivity and selectivity. The structural and functional diversity of the chiral organocatalysts derived from natural and synthetic sources utilized differently the water either as the sole solvent, co-solvent or additive for optimising their best performances. In the present review, we discuss a detailed and comprehensive report on the advancement in the field of asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media.     

Enantioselective synthesis of chiral γ-aryl α-keto ester by copper-catalyzed 1,4-conjugate addition using D2-symmetric biphenyl phosphoramidite ligand

Cu-catalyzed enantioselective 1,4-conjugate addition of β,γ-unsaturated α-keto ester compound was carried out to afford chiral γ-substituted γ-aryl α-keto ester, which could be conveniently converted to the potential skeleton of new Pril drugs. Up to 81% ee and 99% yield were afforded for the 1,4-conjugate addition using D₂-symmetric biphenyl phosphoramidite ligand.     

Furanoside phosphite–phosphoroamidite and diphosphoroamidite ligands for Cu-catalyzed asymmetric 1,4-addition reactions

A sugar-based phosphite–phosphoroamidite and diphosphoroamidite ligand library L1–L5a–g was tested in the asymmetric Cu-catalyzed 1,4-conjugate addition reactions of β-substituted and β,β′-disubstituted enones. Our results indicated that the selectivity was strongly dependent on the ligand parameters and on the substrate structure. Moderate-to-good enantioselectivities (ees up to 84%) were obtained in the 1,4-addition of several types of β-substituted cyclic and linear substrates. Of particular note is the high enantioselectivity (ees up to 90%) obtained for the more challenging β,β′-disubstituted 3-methyl-cyclohexenone.     

A Stereooontrolled Approach to Tri and Tetrasubstttuted Cyclohexanones

A series of reactions utilizing acetals 2–5 with organo cuprates was studied to determine the stereoselectivity of the 1,4-conjugate addition. A90:10 stereoselectivity was observed from the reaction of lithium or bromomagnesium divinyl cuprate with acetal 5 which generated a facile entry to the tetrasubstituted cyclohexanone via a consecutive 1,4-conjugate addition - 1,3-alkylation sequence.     

Synthesis of 5,6,7-trimethylbenz[c]acridine

A new potential carcinogenic aromatic heterocyclic compound, 5,6,7-trimethylbenz[c]acridine ( 1 ), has been synthesized from the known 5,5-dimethyl-6-keto-5,6-dihydrobenz[c]acridine ( 4 ) using a series of reactions which includes an interesting new type of 1,4-conjugate addition cmploying lithium dimethylcopper.     

Enantioselective copper-catalyzed conjugate addition using chiral diaminocarbene ligands

Chiral diaminocarbene ligands, generated by in-situ deprotonation of the corresponding chiral imidazolinium salts, are shown to be efficient ligands in the asymmetric copper-catalyzed 1,4-conjugate addition of diethylzinc to enones, allowing enantiomeric excesses of up to 51% to be achieved.     

Asymmetric synthesis of pent-3-yl (R)-6-methyl-cyclohex-1-ene carboxylate

An expeditious asymmetric synthesis of pent-3-yl (R)-6-methyl-cyclohex-1-enecarboxylate has been achieved in four steps in 42% overall yield employing as the key step a domino reaction initiated by a highly diastereoselective lithium amide 1,4-conjugate addition to a nona-2,7-diendioic diester followed by a 6-exo-trig cyclisation of the thus formed enolate. Cope elimination protocol of the cyclic adduct affords, depending on the lithium amide used, the corresponding nitro-compound or the expected cyclohexene derivative. The methyl group attached to the cyclohexane ring is achieved by selective ester hydrolysis and subsequent Barton decarboxylation.