酰胺直接转化:策略与近期进展

以酰胺直接转化的C-C键形成方法为主线,简要回顾近年取得的主要突破.内容涵盖基于三氟甲磺酸酐活化、化学选择性试剂的还原官能化策略,以及两类催化转化.这些重要进展表明温和条件下的酰胺转化可达到优异的化学选择性、官能团容忍性和较好的底物普适性,转化产物还包括多种官能化的胺、酮和烯胺酯（酮）化合物等,并已在天然产物和生理活性化合物的合成中得到应用与检验.     

钯配合物与手性方酰胺协同催化的乙烯基碳酸乙烯酯与醛的不对称脱羧环加成反应

利用金属钯与非手性膦配体原位生成的钯配合物和手性方酰胺为协同催化体系实现了乙烯基碳酸乙烯酯（VECs）与甲醛的不对称脱羧环加成反应,以良好的产率和对映选择性得到了手性叔醇类化合物.发现了有机小分子催化剂-手性方酰胺可实现该反应的不对称诱导,为通过两性离子烯丙基钯中间体的环加成反应的研究提供了新的思路.     

环加成反应、环合反应、电环化反应与环化反应的区别*

环加成反应、环合反应、电环化反应与环化反应都是合成有机环状化合物的成环反应,它们描述的反应类型完全不同。但是,它们却经常被误用或者混用。阐述了这4类反应的区别,希望能够从教学上明确这4类反应,从源头为将来的有机化学工作者建立起准确的概念。     

1-(SR)-对甲苯亚磺酰基-3-戊烯-2-酮与环戊二烯的不对称催化环加成反应

前文曾报道了α-苯磺酰基-α,β-不饱和酮作为双烯体和亲双烯体所进行的不对称催化HeteroDiels-Alder反应^[1]和Diels-Alder反应^[2].为深入研究其反应机理,提出反应过渡态模型和鉴定环加成物构型.     

硅烯与甲醛环加成反应的理论研究

本文用RHF/6-31G^*解析梯度方法研究了单重态硅烯与甲醛环加成反应的机理,用二级微扰方法对各构型的能量进行了相关能校正,并用统计热力学方法和过渡态理论计算了该反应在不同温度下的热力学函数的变化和动力学性质。结果表明,此反应历程由两步组成:1)硅烯与甲醛生成一中间配合物,是一无势垒的放热反应,2)中间配合物异构化为产物,此步势垒经零点能校正后只有51.4kJ·mol^-^1(MP2/6-31G^*//6-31G^*);从热力学和动力学的综合角度考虑,该反应在300～400K温度下进行为宜,如此,反应既有较大的自发趋势和平衡常数,又具有较快的反应速率。     

六氟锑酸催化环乙亚胺与炔烃的[3+2+2]环加成反应合成Azepines

正Angew.Chem.Int.Ed.2014,53,4196~4199环加成反应是构建环状化合物最为重要的方法之一,具有良好的选择性和高效的原子经济性等特性,因而在有机合成中占有十分重要地位.纵观已报道的环加成反应,主要工作依旧聚焦在两分子间的环加成反应.虽然通过三组分等多组分的环加成反应可以构建较大环的环状化合物,但面临挑战,例如反应选择性控制,包括化学选择性(生成五元环或六元环等的竞争)和区域选择性等方面.为解决这一难题,湖南大学化学化工学院李金恒研究小组通过控     

二(苯磺酰)一氟甲烷试剂对醛的加成反应:锂—氧原子络合和氟原子取代对碳—碳键形成的关键作用

随着氟元素在医药和农药中不断被广泛应用,新型高效的氟化试剂和氟化反应已成为近年来国际化学界研究热点.自2006年日本Shibata小组和我国胡金波小组几乎同时独立报道二(苯磺酰)一氟甲烷(FBSM)试剂以来,该试剂已成为广为使用的亲核一氟甲基化试剂(见综述:Chem.Commun.2009,7465～7478).然     

4，4-二氯六氟-1-丁烯及其重排产物与亲核试剂加成反应活性的比较研究

本文简要报道了4，4-二氯六氟-1-丁烯及其重排产物与亲核试剂加成反应活性的比较研究。     

用原位变温19F NMR研究三氟甲磺酸根在苯乙烯不对称环丙烷化反应中的作用

The role of trifluoromethanesulfonate ion (OTf -) in asymmetric cyclopropanation of styrene catalyzed by ruthenium complex of chiral N, P ligand is investigated by in situ variable temperature 19 F NMR. The temperature of NMR experiment varies from 243 K to 283 K. After ethyl diazoacetate and styrene are added into the catalytic system, the process that the OTf - leaves from the central metal is observed from the change of the 19 F NMR spectra. Owing to the weakly coordinating behavior, trifluoromethanesulfonate ion can be easily removed from the central metal and replaced by substrates to form the reactive intermediate during the reaction. So that the catalytic reactivity can be improved greatly when the silver trifluoromethanesulfonate is added to the catalytic system.     

仲酰胺经酰胺活化直接合成酮的普适性方法

本文报道仲酰胺经去胺基烷基化反应直接合成酮的通用性方法. 这一新的C-C 键形成方法是基于Tf₂O 对仲酰胺的活化及有机铈试剂对活化所形成活性中间体的加成而实现的. 该方法可用于各种酮的合成, 包括烷基-烷基酮、烷基-芳基酮、芳基-芳基酮、α,β-不饱和酮以及β-氯-α,β-不饱和酮等, 收率65%～90%. 研究表明, 除了有机铈试剂外, 碱性较弱的炔基硼试剂、温和亲核性的烯丙基三甲基硅烷以及低亲核性的苯乙烯均可与仲酰胺的活化中间体进行加成反应, 水解后生成相应的酮. 因此, 该方法具有较好的普适性和重要的合成应用价值. 基于实验结果和验证实验, 提出经由腈鎓中间体的可能反应机理. 本法使仲酰胺成为形式上的酰化试剂, 不但可与有机金属试剂反应, 还可与烯丙基三甲基硅烷和苯乙烯进行还原酰化反应.     

Iridium‐Catalyzed Reductive Alkylations of Secondary Amides

Reported herein is the first direct, metal‐catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups.     

Chemoselective α,β‐Dehydrogenation of Saturated Amides

We report a method for the selective α,β‐dehydrogenation of amides in the presence of other carbonyl moieties under mild conditions. Our strategy relies on electrophilic activation coupled to in situ selective selenium‐mediated dehydrogenation. The α,β‐unsaturated products were obtained in moderate to excellent yields, and their synthetic versatility was demonstrated by a range of transformations. Mechanistic experiments suggest formation of an electrophilic Se^IV species.     

Excess Enthalpies of Binary Mixtures of Formamide with Secondary Amides

The excess molar enthalpies H^E of binary mixtures of formamide with N-methylformamide, N-ethylformamide, N-methylacetamide, N-ethylacetamide and N-methylpropion-amide have been measured as functions of the mole fraction at 308.15 K, using an isoperibol rotating calorimeter. The experimental values of H^E are negative for all mixtures over the whole composition range. Intermolecular interactions in these mixtures are discussed through comparison of the results with those for corresponding binary mixtures of water. This revised version was published online in August 2006 with corrections to the Cover Date.     

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

By exploring a new mode of nickel‐catalyzed cross‐coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α‐trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C? H bond is also presented.     

Study on Unexpected Cycloaddition Reactions of Imines with THF

Thesynthesisofnitrogen-containingheterocylesthroughcycloadditionreactionofimineshasstimulatedmuchpreparativeandmechanisticwork'".Whenweattemptedtosynthesizeapolycycliccompound3byadditionreactionofimineland5-norbornene-2,3-dicarboxylicacid2,however,unexpectedtricycliccompounds4and6wereobtainedinsteadofthedesignedproduct3(Schemcl).Heretetrahydrofuran(THF)servedasthesourceofdihydrofiJranwhichunderwentcycloadditionwithlgiving4and6.Ananalogousreactionwasnotedpreviouslyinthislaboratory'(Scheme2).…     

Copper‐Catalyzed Reductive N‐Alkylation of Amides with N‐Tosylhydrazones Derived from Ketones

A CuI‐catalyzed reductive coupling of ketone‐derived N‐tosylhydrazones with amides is presented. Under the optimized conditions, an array of N‐tosylhydrazones derived from aryl–alkyl and diaryl ketones could couple effectively with a wide variety of (hetero)aryl as well as aliphatic amides to afford the N‐alkylated amides in high yields. The method represents the very few examples for reliably accessing secondary and tertiary amides through a reductive N‐alkylation protocol.