2,3-联烯醇及其衍生物的反应

2,3-联烯醇是一类含1,2-二烯官能团和羟基的化合物, 具有很高的反应活性, 它及其衍生物是一类重要的联烯化合物. 概述了2,3-联烯醇及其衍生物的反应, 包括2,3-联烯醇在过渡金属催化下的自身异构环化反应、钯催化的偶联反应、钌催化的环羰基化反应、不同条件下不同方式的扩环反应、亲电试剂参与的反应、分子内环加成反应、自由基反应等和2,3-联烯醇衍生物在零价钯催化下基于亚甲基-π-烯丙基钯中间体生成联烯或1,3-共轭二烯的区域选择性反应, S_N2'类型的加成-消除反应, 二价钯催化下的分子内环化反应以及重排反应等.     

1,2-联烯亚砜和1,2-联烯砜的反应

1,2-联烯亚砜和1,2-联烯砜是重要的含硫联烯化合物.综述了1,2-联烯亚砜和1,2-联烯砜的亲核加成、亲电加成、Diels-Alder反应、1,3-偶极加成、[2+2]环加成等反应以及在天然产物中的应用.     

邻醌与噁唑的光化[4+4]环加成反应

虽然[2+2]和[4+4]环加成反应都是光化学允许的,但[4+4]环加成远不及[2+2]反应普遍.已知的[4+4]环加成主要为蒽、萘、吡啶-2-酮和吡喃-2-酮衍生物的光化二聚以及它们与某些1,3-二烯的环加成.羰基化合物与烯烃一般发生[2+2]环加成(Peterno-B點hi反应).邻醌和α-二羰基化合物与富电子烯烃则已知可进行[2+2]或[4+2]的光化环加成反应,分别得到α-羰基氧杂环丁烷和1,4-二氧杂环己烯.但未知有光化[4+4]环加成反应.     

[2,3′-联-1H-吲哚]-3(2H)-酮类化合物的单重态氧反应

[2,3’-联-1H-吲哚]-3(2H)-酮衍生物(1a～1c)在甲醇中的单重态氧反应给出溶剂捕捉产物4,后者在分离过程中脱去甲醇分子生成5。考察了标题化合物分子中二氢吲哚酮结构单元以及吲哚结构单元在单重态氧反应中的作用。并探讨了反应机理。     

DDQ介导的新型3-吲哚烷酮及吡喃酮并[2,3-b]吲哚类化合物的合成

以1-(1H-吲哚-3-基)戊烷-3-醇及其衍生物为底物,以三氟甲磺酸铜为催化剂,甲醇为溶剂,DDQ（2,3-二氯-5,6-二氰基对苯醌）为氧化剂,共合成9个新型的3-吲哚烷酮衍生物及5个结构新颖的吡喃酮并[2,3-b]吲哚衍生物,其结构经¹H NMR,¹³C NMR和HR-MS(ESI)表征。对反应机理进行了推测并通过同位素实验进行了验证,反应为碳正离子参与并经分子间和分子内的亲核加成形成碳-氧键的过程。      

镍催化氮杂环丁酮和丁二烯环加成反应机制的理论研究

采用密度泛函理论(DFT)方法对镍催化1-Boc-3-氮杂环丁酮和2,3-二甲基-1,3-丁二烯的环加成反应进行了理论研究. 计算结果表明, 该反应采用氧化加成机制而非实验推测的β-碳消除机制. 氧化加成机制主要由3个基元反应步骤组成, 分别为氮杂环丁酮底物中C—C(=O)键的氧化加成、 二烯顺式插入Ni—C(=O)键、 以及还原消除生成八元氮杂环产物, 其中烯烃插入是整个反应的决速步骤, 反应能垒为86.74 kJ/mol. 通过探讨烯烃分别插入到Ni—C(=O) 键和Ni—C(sp³) 键的2种反应途径分析了烯烃插入步骤的区域选择性, 得到了与实验数据基本一致的结果.     

嘧啶酮衍生物的微波合成

在微波辅助下,Baylis-Hillman加成物与4-氨基-6-氯嘧啶或2-氨基-噻唑反应,快速合成了两类嘧啶酮衍生物——3-取代-7-氯-4H-嘧啶[1,2-b]哒嗪-4-酮和6-取代-5H-噻唑[3,2-a]嘧啶-5-酮,收率81%～98%,其结构经1H NMR,13C NMR,IR和MS确证。     

铜催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应合成手性膦酰化2,3-二氢呋喃

手性2,3-二氢呋喃衍生物是一类重要的杂环化合物,广泛存在于天然产物和生物活性分子中.它们也经常被用于手性四氢呋喃化合物的不对称合成.因此,人们发展了很多合成手性2,3-二氢呋喃化合物的方法,如有机小分子催化的多米诺迈克尔-烷基化反应、“中断的”Feist-Bénary反应或改进的 Feist-Bénary反应.此外,过渡金属催化的手性2,3-二氢呋喃的不对称合成在近些年引起了人们的极大关注. Ozawa等通过 Pd-催化2,3-二氢呋喃的动力拆分方法获得了手性2-芳基-2,3-二氢呋喃. Evans发展了一种 Sc-催化联烯硅和乙醛酸乙酯的[3+2]环加成反应合成手性2,3-二氢呋喃的方法.最近, Fu和 Tang等发展了 Cu催化烯酮和重氮化合物的[4+1]环加成反应合成手性2,3-二氢呋喃的方法.在 Nishibayashi和 van Maarseveen的开创性工作之后, Cu催化的不对称炔丙基转化反应取得了很大的进展.最近,我们发展了一类新的三齿手性 P,N,N-配体,在 Cu催化不对称炔丙基取代、脱羧炔丙基取代、[3+2]、[3+3]和[4+2]环加成反应中表现出优秀的对映和非对映选择性.其中,我们发现采用 Cu催化炔丙醇酯和β-酮酯的[3+2]环加成反应,能高对映选择性地获得手性2,3-二氢呋喃.我们设想,采用β-羰基膦酸酯代替β-酮酯,通过这种 Cu催化[3+2]环加成反应,将可以合成一类具有重要生物活性的手性膦酰化2,3-二氢呋喃化合物.基于这种设想,本文使用手性 P,N,N-配体,通过 Cu催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应,以很好的收率和最高92% ee的对映选择性获得了一系列光学活性的膦酰化2,3-二氢呋喃化合物.我们以炔丙醇酯1a与β-羰基膦酸酯2a为标准底物,优化了反应条件,考察了配体、Cu盐、碱和反应温度等对反应收率和对映选择性的影响.我们确定了最佳的反应条件：以4b为配体,以 Cu(OTf)2为铜盐,以t-BuOK为碱,以 MeOH为溶剂,–20oC反应24 h.在此条件下,我们对β-羰基磷酸酯2的适用范围进行了考察.结果表明,各种苯基取代的β-羰膦磷酸酯均能得到很好的收率和对映选择性.苯环上取代基的空间效应对反应的对映选择性影响不大,但对反应收率影响较大,与相应3-取代或4-取代底物相比较,2-取代的底物获得的收率较低.苯环对位取代基的电子效应对反应的影响不大,给电子基或吸电子基的底物,均得到了较好的收率和对映选择性.杂环取代的底物同样适用于该反应,以90%的收率和89% ee的对映选择性获得了相应的[3+2]环加成产物.对于烷基底物,虽然反应的产率略低,但是得到了高达92% ee的产物.此外,我们对炔丙醇酯底物的适用范围也进行了考察.结果表明,该体系对于各种取代的炔丙醇酯底物均可以获得较高的收率和良好的对映选择性.总之,本文发展了一种铜催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应的方法,成功合成了手性膦酰化2,3-二氢呋喃化合物.通过使用一个结构刚性的酮亚胺三齿 P,N,N-配体,以很好的收率和最高92% ee的对映选择性获得了一系列光学活性的膦酰化2,3-二氢呋喃化合物.     

1，2－联烯亚砚和1，2－联烯砜的反应

1，2－联烯亚砜和1，2－联烯砜是重要的含硫联烯化合物，综述了1，2－联烯 亚砜和1，2－联烯砜的亲核加成、亲电加成、Diels-Alder反应、1，3－偶极加成 、[2+2]环加成等反应以及在天然产物中的应用。     

新型螺[色烯并(2,3-c)吡唑-4,1’-异苯并呋喃]-3’-酮类化合物的合成及光学性能研究

在酸催化及脱水作用下,以2-(4-二丁基氨基-2-羟基苯甲酰基)苯甲酸或2-(4-二乙基氨基-2-羟基苯甲酰基)苯甲酸和吡唑啉酮为原料,通过Knoevenagel缩合和脱水反应,合成了一系列新型螺[色烯并(2,3-c)吡唑-4,1’-异苯并呋喃]-3’-酮类化合物.考察了反应物配比、催化剂、温度和时间等因素对反应的影响,初步探究了所合成化合物在不同pH、溶剂中的光学性能,其中1-(4-氯苯基)-7-(二乙基氨基)-3-甲基-1H,3’H-螺[色烯并[2,3-c]吡唑-4,1’-异苯并呋喃]-3’-酮(1e)和1-(4-氯苯基)-7-(二丁基氨基)-3-甲基-1H,3’H-螺[色烯并[2,3-c]吡唑-4,1’-异苯并呋喃]-3’-酮(1j)有潜力作为强酸强碱的pH指示剂.     

Studies on K2CO3-catalyzed 1,4-addition of 1,2-allenic ketones with diethyl malonate: controlled selective synthesis of beta,gamma-unsaturated enones and alpha-pyrones

The K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized beta,gamma-unsaturated enones 3 or 4 was studied. With 3-unsubstituted 1-substituted-1,2-allenyl ketones, the highly selective formation of beta,gamma-unsaturated enones 4 was observed; with 1,2-allenyl ketones bearing one or two 3-substituents in the allenyl group, only beta,gamma-unsaturated enones 3 with an unmigrated carbon-carbon double bond were produced; with 3-monosubstituted-1,2-allenyl ketones Z-beta,gamma-unsaturated enones 3 were formed with excellent stereoselectivity (E:Z > 96:4); with propadienyl ketones, mixtures of beta,gamma-unsaturated enones 3 and 4 were formed. alpha-Pyrone derivatives were synthesized via the K(2)CO(3)-catalyzed or -promoted reaction of 1,2-allenic ketones with diethyl malonate via a sequential Michael addition-carbon-carbon double bond migration-lactonization process.     

Pd0-catalyzed coupling cyclization reaction of Aryl or 1-alkenyl halides with 1,2-allenyl ketones: scope and mechanism. An efficient assembly of 2,3,4-, 2,3,5-tri- and 2,3,4,5-tetrasubstituted furans

Described herein is the Pd(0)-catalyzed coupling cyclization reaction of 1,2-allenyl ketones with organic halides leading efficiently and conveniently to not only 2,3,4- and 2,3,5-trisubstituted furans but also 2,3,4,5-tetrasubstituted furans. Furthermore, this method showed high substituent-loading capability and tolerance of various substituents. The reactions of 1,2-allenyl ketones 1 e, 1 p, 1 q, and deuterated [D]1 c were performed for a mechanistic study, which demonstrated that instead of an enolization pathway, the reaction may proceed via the intermediacy of dienolate palladium and intramolecular nucleophilic attack on the pi-allyl palladium intermediate by the carbonyl oxygen.     

Palladium-catalyzed cyclization reaction of allylic bromides with 1,2-dienyl ketones. An efficient synthesis of 3-allylic polysubstituted furans

3-Allylic polysubstituted furans were synthesized via a palladium-catalyzed cyclization reaction of allylic bromides with differently substituted 1,2-allenyl ketones. This process may occur via the reaction of a furanyl palladium intermediate with allylic bromide.     

Study of the reaction of 1,1-bis(trimethylsilyl)-2-phenylethylene with some acyl chlorides in the presence of AlCl3

1,1-Bis(trimethylsilyl)-2-phenylethylene (1), which has been synthesized from the Peterson reaction between (Me₃Si)₃CLi and benzaldehyde, reacts with various acyl chlorides (RCOCl, R = Me, Et, iso-Pr, n-Bu, iso-Bu, iso-C₅H₁₁, PhCH₂, PhCH₂CH₂) in the presence of AlCl₃ to give -silyl-,β-unsaturated enones 3a–3h with high E stereoselectivity along with trans-,β-unsaturated ketones 4a–4h. The enones 3 can be partially converted into the ketones 4 with an excess of AlCl₃. Reaction of 1 with RCOCl, (R = Ph, CH₃CH=CH) afforded only the ketones 4. Yields were dependent on time and the amounts of AlCl₃ used.     

Regioselective reductions of β,β-disubstituted enones catalyzed by nonracemically ligated copper hydride

CuH-catalyzed 1,2-additions to β,β-disubstituted α,β-unsaturated ketones have been further explored. Asymmetric reductions of enones lacking an α-substituent can be achieved with CuH complexed by DTBM-SEGPHOS in Et₂O at ?25 °C leading to the generation of highly valuable nonracemic allylic alcohols. The corresponding 1,4-reductions can also be achieved using the same reaction conditions by switching the ligand to a JOSIPHOS analog affording nonracemic β,β-disubstituted ketones. DFT calculations of the enone conformations and transition-state energies for model 1,2- and 1,4-additions were carried out to clarify the factors affecting the product ratios.     

Studies on t-BuOK-catalyzed Michael addition of 1,2-allenic ketones with 2-substituted diethyl malonates: highly selective synthesis of β,γ-unsaturated enones

In this paper, we have demonstrated a facile nucleophilic addition of 2-substituted diethyl malonate to various substituted 1,2-allenic ketones to afford β,γ-unsaturated enones using a catalytic amount of t-BuOK as the base. The reaction usually completes within 10 min in acetone at room temperature. The stereoselectivity of the reaction with γ-substituted allenic ketones is very high affording the β,γ-unsaturated E-enones.     

Highly selective hydrohalogenation reaction of substituted 2,3-allenoates

The hydrohalogenation reaction of 1-alkyl substituted 1,2-allenyl carboxylic acid esters (1) with MX (M= Na, or Li, X= Cl, Br, I) afforded a mixture of (5,7-unsaturated 3-halo-3-alkenoates (2) and α,β-unsaturated 3-halo-2-alkenoates (3) in HOAc, while using a mkture of HOAc-CF3CO2H (1:1) or CF3CO2H as the reaction medium the corresponding reaction cleanly produced β,γ-unsaturated 3-halo-3-alkenoates (2) as the sole products in high yields. The subsequent coupling reactions were studied.     

Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols

A Bi(OTf)₃-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino ketones, were obtained through tandem Meyer-Schuster rearrangement reaction of propargyl alcohols and intermolecular Michael addition of α, β-unsaturated ketones and sulfonamide. Then the in situ generated α-halo-β-amino ketones underwent the base-promoted intramolecular cyclization to give diverse acyl aziridines in a one-pot fashion. These transformations are reliable on a large scale. The high yields and convenient experimental operations make it a valuable method for the construction of α-halo-β-amino ketones and acyl aziridine derivatives.     

A convenient approach to β-heteroarylated (C-N bond) ketones from Cs2CO3 promoted reaction between propargyl alcohols and nitrogen-heterocycles

An efficient and direct approach to β-heteroarylated (C-N bond) ketones is demonstrated. Base promoted redox isomerization of propargyl alcohol to α,β-unsaturated ketone followed by conjugate addition to NH-heteroarenes affords a wide range of β-heteroarylated ketones in good to excellent yields. Aryl, heteroaryl, alkyl C(sp), and terminal alkynes containing unactivated propargyl alcohols effectively undergo redox-isomerization conjugate addition (RICA) with NH-heteroarenes. Reaction of 3-substituted pyrazoles or indazole with propargyl alcohols enables highly regioselective products. A diverse range of NH-bearing nucleophiles such as: pyrazoles, imidazole, triazoles, pyrrole, indoles and aniline participate in this reaction and deliver the corresponding β-heteroarylated ketones.