The catalysis of the electrochemical reduction of alkyl bromides by nickel complexes: The formation of carboncarbon bonds

The square planar, macrocyclic nickel complex, N, N′-ethylenebis(salicylideneiminato)nickel(II), is shown to be an effective catalyst for the electrochemical reduction of substituted alkyl bromides; this indirect cathodic reduction can lead to a good yield of dimeric products. The reduction of alkyl bromides in the presence of an activated olefin is shown to lead to mixtures of products compatible with radical addition to the double bond. The mechanism of the reaction of nickel(I) complexes with alkyl bromides is discussed in the light of these results.     

烯基取代的甲酸态四氢叶酸辅酶模型的合成及其碳单元转移反应

以邻苯二胺和乙酸为原料,经3步反应合成了8种烃基乙烯基取代的苯并咪唑盐,其结构用元素分析,¹HNMR,IR,MS和UV-Vis进行了表征,并以其作为取代的甲酸态四氢叶酸辅酶模型,同亲核试剂(格氏试剂)反应得到烃基乙烯基取代的一碳单元完全转移的产物α,β-不饱和酮,为α,β-不饱和酮的合成提供了一种简便的仿生合成新方法.     

CuI/Oxalamide Catalyzed Couplings of (Hetero)aryl Chlorides and Phenols for Diaryl Ether Formation

Couplings between (hetero)aryl chlorides and phenols can be effectively promoted by CuI in combination with an N‐aryl‐N′‐alkyl‐substituted oxalamide ligand to proceed smoothly at 120 °C. For this process, N‐aryl‐N′‐alkyl‐substituted oxalamides are more effective ligands than bis(N‐aryl)‐substituted oxalamides. A wide range of electron‐rich and electron‐poor aryl and heteroaryl chlorides gave the corresponding coupling products in good yields. Satisfactory conversions were achieved with electron‐rich phenols as well as a limited range of electron‐poor phenols. Catalyst and ligand loadings as low as 1.5 mol % are sufficient for the scaled‐up variants of some of these reactions.     

Irreversible endo‐Selective Diels–Alder Reactions of Substituted Alkoxyfurans: A General Synthesis of endo‐Cantharimides

The [4+2] cycloaddition of 3‐alkoxyfurans with N‐substituted maleimides provides the first general route for preparing endo‐cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2‐substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead‐like properties for medicinal chemistry programs. Furthermore, the electron‐rich furans are shown to react with a variety of alternative dienophiles to generate 7‐oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3‐alkoxy group on a furan Diels–Alder reaction.     

3+2] versus [4+2] cycloadditions of quinone monoimide with azadienes: a Lewis acid-free access to 5-amino-2,3-dihydrobenzofuranes

The reaction between p-quinone monoimide 1a and various azadienes 2 is described in the absence of a Lewis acid promoter. When alpha,beta-unsaturated hydrazones are substituted by proton or alkyl groups, 2,3-dihydrobenzofuranes 4, a motif that is present in numerous biologically active products, are obtained in moderate to excellent yields. The regio- and stereoselectivity of this reaction has been proved by a complete NMR study, including 1H-15N correlations.     

Novel Tetraindoles and Unexpected Cycloalkane Indoles from the Reaction of Indoles and Aliphatic Dialdehydes

The reaction of indoles with dialdehydes was studied for the first time. Mild reaction conditions using glacial acetic acid led to two novel kinds of reaction products: one designated as alkyl chain‐connected tetraindoles and the other one as bis(indolyl)‐substituted cycloalkane indoles. The suggested reaction pathways are discussed. The indole substituents of the cycloalkane indoles were either trans or cis orientated depending from the alkyl chain length.     

Manganese‐Catalyzed Dehydrogenative Alkylation or α‐Olefination of Alkyl‐Substituted N‐Heteroarenes with Alcohols

Catalysis with earth‐abundant transition metals is an option to help save our rare noble‐metal resources and is especially interesting when novel reactivity or selectivity patterns are observed. We report here on a novel reaction, namely the dehydrogenative alkylation or α‐olefination of alkyl‐substituted N‐heteroarenes with alcohols. Manganese complexes developed in our laboratory catalyze the reaction with high efficiency whereas iron and cobalt complexes stabilized by the same ligands are essentially inactive. Hydrogen is liberated during the reaction, and bromine and iodine functional groups as well as olefins are tolerated. A variety of alkyl‐substituted N‐heteroarenes can be functionalized, and benzylic and aliphatic alcohols undergo the reaction.     

Highly modulated bisindoles: ligands for copper‐catalyzed Sonogashira reaction

Bisindoles (BIMs) were modulated as powerful N,N′ donor ligands for the copper‐catalyzed Sonogashira reaction. Ligand screening experiments on 11 BIM compounds found that 3,3′‐(4‐chlorophenyl)methylenebis(1‐methyl‐1H‐indole) (10%) efficiently accelerated CuCl (5%)‐catalyzed cross‐coupling of aryl iodides with terminal alkynes. A wide range of substituted aryl iodides and/or alkyl‐ and aryl‐substituted terminal alkynes were examined, leading to the corresponding coupling products with yields up to 99%. An efficient and scalable protocol for the synthesis of BIM ligands on a gram scale, with extremely low catalyst loading of o‐ClC₆H₄NH₃⁺Cl^?, was also developed with a reaction time of 20 min with yields up to 93%. This novel N,N′ ligand was air‐stable, easily available and highly modulated with low copper loading. Copyright © 2016 John Wiley & Sons, Ltd.     

Chemical investigations of citraconimide

The chemical reactivity of citraconimide (3-methylmaleimide, 2 ) has been investigated with special emphasis being placed on the use of mild and selective reaction conditions. Particular attention has been focused on the theiotropic reactivity of citraconimide. The results indicate that the reaction of various mercaptans with citraconimide is highly regioselective resulting predominately in the geminally substituted products with the percentage of vicinally substituted products increasing as a function of the steric bulk of the alkyl mercaptan. Additional studies on the double bond of citraconimide have furnished 4-halogeno- and the 3,4-dihydro derivatives of citraconimide. Several N-substituted citraconimide derivatives have also been prepared.     

A rapid and efficient method for the reduction of quinoxalines

Mono and di‐substituted alkyl and aryl quinoxalines are rapidly reduced in high yield to their respective 1,2,3,4‐tetrahydro‐derivatives by borane in THF solution. In the case of the 2,3‐di‐substituted compounds, reduction is stereoselective yielding exclusively the cis‐isomers. Sodium borohydride in acetic acid also reduces alkyl and aryl quinoxalines, but proceeds with lower yields and often produces side products. Sodium borohydride in ethanol reduces quinoxaline and 2‐methylquinoxaline in high yield; however, the reaction is very slow, whereas 2,3‐dialkyl and 2‐aryl quinoxalines are not efficiently reduced by sodium borohydride in ethanol.     

Alkylation of diene allylic tertiary amines with grignard reagents. In situ activation with alkyl chloroformates.

Diene allylic tertiary amines were substituted with Grignard reagents in the presence of lithium tetrachlorocuprate and alkyl chloroformates. According to the experimental condition employed, this reaction afforded exclusively δ-1 V-alkylation products.     

Radical addition to 1,4-benzoquinones: addition at O- versus C-atom

Addition of alkyl radicals generated from B-alkylcatecholboranes onto 1,4-benzoquinones leads to substituted hydroquinones in good overall yields. Formation of aryl ethers via a unique radical addition to the oxygen atom of the enone system is the main reaction when bulky secondary and tertiary alkyl radicals are used. Less hindered secondary and primary radicals give the expected 1,4-conjugate addition products. [reaction: see text]     

Isocyanide‐Based Multicomponent Reaction: One‐Pot Synthesis of New Derivatives of Iminofuranone

The one‐pot multicomponent reaction of alkyl isocyanide, alkylidene‐substituted Meldrum's acid, and arylcarboxylic acids affords new derivatives of iminofuranone in fair yields. The structure of the products was deduced from their spectroscopic data. Two equivalents of the respective isocyanides participate in this reaction.     

Br?nsted酸催化N1-对甲基苯磺酰基三唑与烯烃加成合成高N2选择性的烷基-1,2,3-三唑

N-取代基-1,2,3-三唑广泛应用于生物科学、材料化学和药物化学领域,近几年来引起了人们很大兴趣. N1-取代基-1,2,3-三唑既可由加热催化,也可通过金属诱导的(铜(Ⅰ)催化的1,4-双取代和钌(Ⅱ)催化的1,5-双取代)1,3偶极子环加成反应制备得到,然而有关N2-取代基-1,2,3-三唑的合成仍未获得太大进展.目前,高N2选择性的N2-芳基和N2-烯丙基-1,2,3-三唑的合成方法是利用大位阻的膦配体配位钯催化偶联反应.2008年,史晓东课题组报道了烷基卤化物与大体积的 C-4和 C-5双取代基的NH-1,2,3-三唑通过亲核反应合成N2-烷基-1,2,3-三唑,但其应用受到底物限制.我们设想N1-烷基-1,2,3-三唑可否由N1-取代1,2,3-三唑合成,由于N1-取代基-1,2,3-三唑制备的研究较多,其合成方法将可很方便地构造N2-烷基-1,2,3-三唑化合物.鉴于此,本文对单取代三唑、未取代三唑与包括乙烯基酯在内的多种烯烃的反应进行了研究.首先,我们用不同取代基的N1-1,2,3-三唑与烯烃在不同的酸催化条件下进行反应,考察了酸效应对反应收率的影响,发现 TsOH做 Br?nsted酸为催化剂时,反应产率最高;而 AuCl3做 Lewis酸为催化剂时反应几乎没有加成产物生成.然后,以 TsOH为催化剂,改变三唑与烯烃的加入比例,发现加入比例为1：6时反应产率最高.当N1取代基是 Ts-时,反应产率最高.催化剂 TsOH的加入量由1当量升至2当量时,反应产率没有明显变化.由此表明,N1-1,2,3-三唑与烯烃的最佳反应条件为：催化剂为 TsOH(1当量),N1-1,2,3-三唑的取代基为 Ts,N1-1,2,3-三唑与烯烃的加入比例为1：6.在确定了最佳反应条件后,考察了三唑类底物的适用性.结果发现, N2/N1产物的比例均很高,说明该反应具有很高的N2选择性.上述研究表明, TsOH酸催化N1-对甲苯磺酰基-1,2,3-三唑与烯烃的加成反应是一种有效合成N2-烷基-1,2,3-三唑的新方法,并通过单晶确定了最终的产物结构.单取代三唑和未取代三唑与包括乙烯基酯在内的多种烯烃反应合成N2-烷基-1,2,3-三唑都有很好的反应效果.本文提供了一种简单有效的合成N2-烷基-1,2,3-三唑的新方法.     

A Simple Synthesis of Polyfunctionalized 4‐Aminopyrazolidin‐3‐ones as ‘Aza‐deoxa’ Analogs of D‐Cycloserine

A simple five‐step synthesis of fully substituted (4RS,5RS)‐4‐aminopyrazolidin‐3‐ones as analogs of D ‐cycloserine was developed. It comprises a two‐step preparation of 5‐substituted (4RS,5RS)‐4‐(benzyloxycarbonylamino)pyrazolidin‐3‐ones, reductive alkylation at N(1), alkylation of the amidic N(2) with alkyl halides, and simultaneous hydrogenolytic deprotection/reductive alkylation of the primary NH₂ group. The synthesis enables an easy stepwise functionalization of the pyrazolidin‐3‐one core with only two types of common reagents, aldehydes (or ketones) and alkyl halides. The structures of products were elucidated by NMR spectroscopy and X‐ray diffraction.     

Hypervalent Iodine(III)‐Mediated Benzannulation of Enamines with Alkynes: an Efficient Synthesis of Substituted Aminonaphthoic Acid Derivatives

An intermolecular two C? C bond formation procedure for the synthesis of carbocycles mediated by hypervalent iodine(III) reagents was developed. This metal free protocol provided a new approach for the synthesis of useful substituted 1‐amino‐2‐naphthoic acid derivatives via benzannulation reactions. Various N‐unsubstituted and N‐alkyl substituted aromatic enamines with terminal alkynes and non‐terminal alkynes can be converted into corresponding 1‐amino‐2‐naphthoic acid derivatives under mild reaction conditions. When meta‐substituted phenyl enamines were employed in the reaction, two cyclization paths were detected in the reaction and ortho‐cyclization products were the only or major products. Good functional group tolerance, readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.     

A green and highly efficient alkylation of thiols in water

An environmentally benign and efficient process for the preparation of thioethers was developed by simple and practical reactions of alkyl halides and thiols in water in the presence of K₂CO₃ or Et₃N in very high yields. The reaction of aryl, alkyl, aliphatic and hindered thiols with various alkyl halides gave the corresponding products with significant advantages such as high conversions, short reaction time, mild reaction conditions, and low cost, simple workup with good to quantitative yields.     

Imidovanadium(v) complexes as reaction partners for kinetically stabilized phosphaalkynes: synthesis of 1,2,4-azaphosphavanada(v)-cyclobutenes, 1,3,5-triphosphabenzenes, and 1H-1,2,4-azadiphospholes

Cycloaddition reactions of the kinetically stabilized phosphaalkynes 1 with the imidovanadium(v) trihalides 9 furnish the 1,2,4-azaphosphavanada(v)cyclobutenes 10. The stability of these novel metallacyclic compounds depends solely on the substitutents of the imido unit. Thus, the imidovanadium(v) species 9 with tertiary alkyl groups on the N atom form stable addition products with 1 while in the cases of compounds 9 with a lower degree of substitution at N (primary and secondary alkyl groups) the primarily formed adducts 10 undergo irreversible decomposition to afford the 1H-1,2,4-azadiphospholes 13. Reactions of an excess of the phosphaaalkyne 1 with the vanadium complexes 9 furnish the corresponding triphosphabenzenes 8 in good yields (36-68%). A catalytic reaction course has been demonstrated for the all-tert-butyl system 1a/9a in which the metallacyclic species 10a serves as the catalytically active species. Poisoning of the catalyst leads to a second reaction pathway, which results in formation of the azatetraphosphaquadricyclanes 16. By means of the stepwise use of different phosphaalkynes 1a,b this methodology provides the first access to the differently substituted triphosphabenzenes through cyclotrimerization.     

Reactions of azirines with sulfur nucleophiles. 4. Treatment of 2H-azirine with mercaptosubstituted acids. reactions of aziridinyl alkyl sulfides with carboxylic acids and acyl chloride derivatives

Treatment of 2H-azirines with mercaptosubstituted acids and their derivatives leads to -ketoamides and 2-aziridinyl alkyl sulfides, respectively. 2-Aziridinyl alkyl sulfides, in turn, react with carboxylic acids to give -ketoamides and substituted ethanethiol derivatives. Acylation of 2-aziridinyl alkyl sulfides with acyl halides generates a variety of products, depending on the reaction conditions; either products derived from cleavage and isomerization of the aziridinyl ring or (1-acylaziridinyl-2) alkyl sulfides are obtained.For communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 206–211, February, 1986.     

Copper-Catalyzed Enantioconvergent Radical C(sp3)−N Cross-Coupling: Access to α,α-Disubstituted Amino Acids

Transition-metal catalyzed enantioconvergent cross-coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α-disubstituted amino acids. However, the construction of chiral C−N bonds between tertiary-carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper-catalyzed enantioconvergent radical C−N cross-coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N-ligand with a long spreading side arm. An array of α,α-disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α-fully substituted amine building blocks.