Asymmetric Conjugate Addition of Unmodified Cyclic Ketones to Nitroolefins Using Aminophosphonate as the Organocatalyst

本文设计合成了光学纯吡咯烷基磷酸酯,并成功地应用于酮类底物与b-硝基芳基乙烯衍生物的不对称催化Michael加成反应中。在20 mol %催化剂用量下,以10 mol %三氟乙酸作为添加物,无溶剂条件下,0 oC反应7-24小时,Michael加成产物的收率最高达96%,非对映选择性最高可达97:3,ee值最高可达90%。     

Organocatalytic Enantio‐ and Diastereoselective Conjugate Addition to Nitroolefins: When β‐Ketoamides Surpass β‐Ketoesters

Our findings on the bifunctional squaramide‐catalyzed enantioselective conjugate addition of β‐ketoamides to nitroolefins are disclosed. It appears that simple acyclic methylene β‐ketoamides, unlike the extensively studied β‐ketoesters, afford the products in excellent diastereoselectivities, and maintain high yields and enantioselectivities. Moreover, competition and kinetic studies were conducted to rationalize the observed reactivity and selectivity. The high level of diastereocontrol, along with the amenability of the amide group to postfunctionalization, dramatically increase the synthetic usefulness of the transformation.     

Michael Addition Initiated Carbocyclization Sequences with Nitroolefins for the Stereoselective Synthesis of Functionalized Heterocyclic and Carbocyclic Systems

The synthesis of various heterocycles and carbocycles (tetrahydrofurans, pyrrolidines, cyclopentanes) has been achieved by using new and efficient ionic addition/cyclization sequences. Nitroolefins play an important role in the Michael addition induced ring‐closing reactions (MIRC) reported in the present article, with various substituted alcohols, amines, Grignard reactants, or malonate derivatives acting as the nucleophile partner. The optimized cascade reactions were high yielding in most cases and highly stereoselective, creating up to three stereogenic centers starting from achiral substrates.     

Enantio‐ and Regioselective Conjugate Addition of Organometallic Reagents to Linear Polyconjugated Nitroolefins

The copper‐catalysed conjugate addition of trialkylaluminium and dialkylzinc reagents to polyconjugated nitroolefins (nitrodiene and nitroenyne derivatives) is reported. A reversed Josiphos ligand L7 allows for the selective 1,4‐ or 1,6‐addition with high enantioselectivities.     

Mechanism of Remote Conjugate Addition of Lithium Organocuprates to Polyconjugated Carbonyl Compounds

Regioselective reaction of a lithium organocuprate (R₂CuLi) and a polyconjugated carbonyl compound affords a remote‐conjugate‐addition product. This reaction proceeds particularly cleanly when the conjugation is terminated by a C? C triple bond. The reaction pathways and the origin of the regioselectivity of this class of transformations are explored with the aid of density functional calculations. The outline of the reaction pathway is as follows. An initially formed β‐cuprio(III) enolate intermediate undergoes smooth copper migration along the conjugated system. This process takes place faster than reductive elimination of intermediary σ/π‐allylcopper(III) species, since the latter reaction disrupts the conjugation in the substrate and hence is not preferred. The copper migration to the acetylenic terminal affords a σ/π‐allenylcopper(III) intermediate, which undergoes facile and selective C? C bond forming reductive elimination at the terminal carbon atom. The present mechanistic framework shows good agreement with some pertinent experimental data, including ¹³C NMR chemical shifts and kinetic isotope effects.     

Catalysis by Lithium Perchlorate Enables Double-Conjugate Addition of Electron-Deficient Maleimides to 2-Aminopyridines and 2-Aminothiazoles

Lithium perchlorate has been found to catalyze the conjugate addition of maleimides with 2-aminopyridines and 2-aminothiazoles. The reaction proceeds under mild conditions leading to the corresponding double adducts in good yields. A plausible mechanism of this reaction has been proposed.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® to view the free supplemental file.     

手性磷酸催化芳香胺与硝基烯烃的不对称加成反应

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％.     

Enantioselective and Regioselective Organocatalytic Conjugate Addition of Malonates to Nitroenynes

The first catalytic asymmetric conjugate addition of 1,3‐dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid‐based thiourea organocatalysts has been developed. The 1,4‐addition adducts were obtained solely, in moderate to good yields (up to 93 %) with good enantioselectivities (up to 99 % ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral β‐alkynyl acid derivatives and synthetically useful chiral nitroalkynes. Notably, the protocol worked well with both aryl‐ and alkyl‐substituted alkynyl substrates.     

L-丙氨酰Betti碱催化环己酮对硝基烯不对称Michael加成反应

合成了3个手性Betti碱的L-丙氨酰衍生物, 并用它们来催化环己酮与硝基烯的Michael加成反应. 发现1a是其中最有效的催化剂, ee值最高大于99%, dr值最高大于99∶1. 考察了催化剂结构与用量、添加剂用量、底物结构等因素对反应的化学产率和光学收率的影响.     

铌酸锂、钽酸锂晶体的结构特征

从铌酸锂和钽酸锂晶体的结晶学数据出发,分析其结构特征和组成化学键的结合情况.对于这两个晶体的结晶学格位占有情况和阳离子的位移进行了理论上的分析.作者首次明确地给出了铌酸锂和钽酸锂晶体中与晶体组成有关的阳离子位移趋势.     

硫脲催化硝基烯与硫叶立德的不对称Michael加成反应

基于密度泛函理论研究了氯代苯基硫脲催化的硝基苯乙烯与硫叶立德的Michael加成反应,确定了控制反应立体选择性的C―C键形成步骤的过渡态结构,计算了过渡态的相对能量和反应势垒,弄清了硫脲催化的微观反应机理,探讨了硫脲催化性能的微观本质.结果表明,反应有利于反式Michael加成产物的形成,硫脲在反应中作为质子给体,首先与质子受体硝基苯乙烯形成双氢键配合物,通过授受体间的电荷转移活化硝基苯乙烯的β-C原子增强其亲电性,有利于硫叶立德的亲核进攻.     

结构简单的4-羟基脯氨酰胺高效催化醛和硝基烯不对称迈克尔加成反应

开发了两种结构简单的反式-4-羟基-L-脯氨酰胺有机小分子催化剂,用于高效催化不对称迈克尔加成反应。在醛和硝基烯的不对称迈克尔加成反应中,以（S）-1,1’-联-2-萘酚为协同催化剂,对两种脯氨酰胺衍生物的催化活性进行研究,发现催化剂摩尔分数仅为0.5%～1%时,产物的收率最高可达96%,非对映和对映选择性值最高可达99/1和99%。该方法为开发低成本、高效率的不对称迈克尔加成反应有机催化剂体系提供了简单易行的选择。     

Sc(OTf)3: A Highly Efficient and Renewable Catalyst for Michael Addition of Indoles to Nitroolefins in Water

A catalytic amount of scandium trifluoromethanesulfonate [Sc(OTf)₃] (2.5 mol%) was used to catalyze the Michael addition of indoles to nitroolefins in water to afford the corresponding 3-alkylated indoles in good to excellent yields. The short reaction times, excellent yields, and renewability of the catalyst are noteworthy.     

Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide

The tripeptide H‐d Pro‐Pro‐Asn‐NH₂ is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide‐like compounds. ¹H NMR spectroscopic, crystallographic, and computational investigations provided insight into the conformational properties of H‐d Pro‐Pro‐Asn‐NH₂ and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective C?C bond formation.     

Copper‐Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl‐N‐methylimidazole Michael Acceptors: a Powerful Synthetic Platform

An efficient copper‐catalyzed enantioselective conjugate addition of dimethylzinc to α,β‐ and α,β,γ,δ‐unsaturated 2‐acyl‐N‐methylimidazoles has been achieved using a chiral bidentate hydroxyalkyl‐NHC ligand. The reactions proceeded with both excellent regio‐ and enantioselectivity (14 examples, 87–95 % ee) to afford the desired 1,4‐adducts, which were easily transformed to the corresponding aldehydes, esters, and ketones. Subsequently, this powerful methodology was therefore successfully applied in the synthesis of natural products. Furthermore, an iterative process was also disclosed leading to highly desirable 1,3‐desoxypropionate skeletons (up to 94 % d.e.).     

Asymmetric Conjugate Addition of Ketones to Maleimides Organocatalyzed by a Chiral Primary Amine-Salicylamide

Enantioenriched substituted succinimides are interesting compounds, and their asymmetric organocatalytic synthesis by the conjugated addition of ketones to maleimides has been scarcely explored. This study shows the enantioselective conjugate addition of ketones to maleimides organocatalyzed by a simple primary amine-salicylamide derived from a chiral trans-cyclohexane-1,2-diamine, which provides the desired succinimides in good to excellent yields (up to 98%) and with moderate to excellent enantioselectivities (up to 99%).