导向有机合成的金属有机化学研究初探

总结了麻生明自1997年回国后在国家自然科学基金委、科技部、中国科学院、上海市科委的共同资助下开展的一些研究工作：(1)联烯化学;(2)偶联反应的区域选择性研究-1-芳基-1-炔烃的单锂化反应;(3)多中心反应-1,1-二溴-1-烯烃的氧化加成反应,α-脱卤钯化反应和分子内双环钯碳化反应。     

藉镍催化的1,1-二溴-1-烯烃与卤代芳烃的类Sonogashira反应合成二取代炔烃

很容易从醛和四溴化碳及三苯膦反应制备的1,1-二溴-1-烯烃在有机合成中是一个非常重要的原料.它广泛地应用于在钯催化下与有机硼酸、有机锡化合物、炔烃、有机锌试剂和Grignard试剂的交叉偶联反应[1-4].除此之外,1,1-二溴-1-烯烃与三丁基锡化氢的氢解反应,1,1-二溴-1-烯烃被氢负离子的还原,1,1-二溴-1-烯烃与金属钐和二碘化钐进行的还原脱溴反应,1,1-二溴-1-烯烃与胺的反应业已报道[5,6].Shen近来研究了钯催化下1,1-二溴-1-烯烃在不同膦配体的存在下于DMF溶液中的自身偶联反应和与末端炔烃的交叉偶联反应[7].     

1,1-二溴-1-烯烃在有机合成中的研究进展

1,1-二溴-1-烯烃作为一类重要的有机合成原料和中间体,已被应用于C—C、C—N、C—O、C—P和C—S键的构建.二溴烯烃分子中包含一对活泼的C—Br键,使其在制备溴代烯烃、溴代炔烃、端炔和通过经典的偶联反应制备多取代的烯烃、内炔和稠环化合物等的反应中应用广泛.综述了1,1-二溴-1-烯烃在有机合成中的研究进展.     

含四硫富瓦烯大环化合物的合成与研究进展

简要介绍了含有四硫富瓦烯(TTF)单元的大环化合物的分类, 概括了各类含四硫富瓦烯大环化合物的合成方法, 主要包括含有1,3-二硫杂环戊烯-2-硫酮单元的大环化合物在亚磷酸三烷基酯参与下的偶合反应, 以及带有氰乙基硫等取代基的预先合成的官能化TTF与二卤代低聚醚的反应. 综述了含四硫富瓦烯大环化合物的电化学性能及其在分子识别方面应用研究的最新进展, 提出了含四硫富瓦烯大环化合物的发展趋势.     

不饱和烃杂钯化反应在有机合成中的应用

不饱和烃杂钯化反应是合成高活性反应中间体烷基钯(II)和烯丙基钯(II)重要的途径. 这些钯的络合物, 在合适的条件下能被各种亲核试剂例如烯丙基卤、一氧化碳、不饱和烃、有机硼、有机锡等捕获. 经过一系列插入及消除反应, 能够有效地构建多种生理活性药物、有机功能分子以及重要合成骨架. 近年来, 引起了有机合成工作者的兴趣. 在这里, 对杂钯化最新进展进行综述.     

(E)-烯二炔化合物的高选择性合成

3-烯-1,5-二炔是许多烯二炔类抗癌抗生素和发光材料的重要片断. 发展了一种高选择性合成E-烯二炔化合物的两步法: (1) CuBr₂为卤化剂, 温和高效合成双卤代烯烃; (2)通过双卤代烯烃和末端炔烃的Sonogashira偶联反应构建烯二炔化合物.     

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.     

钯催化卤代芳烃的胺化反应的研究进展

钯催化卤代芳烃的胺化是合成芳胺化合物的重要方法,综述了近年来钯催化卤代芳烃与胺等不同含氮化合物的胺化反应研究进展,重点讨论了钯催化剂配体的结构、反应物比例、溶剂及温度等因素对反应的影响.     

α,α'-双亚甲基锆杂环戊烷的构建及其在1,5-己二烯合成中的应用

锆杂环化合物因其多种反应活性而备受关注.2分子1,1-二取代联烯在低价锆物种"Cp2Zr(II)"作用下可发生分子间还原偶联形成α,α'-双亚甲基锆杂环戊烷,反应的区域及立体化学受到取代基空间效应影响显著.α,α'-双亚甲基锆杂环戊烷中含有两个sp2碳-金属键,与多种亲电试剂体系反应分别生成多种类型有机分子,可为2,5-二卤代-1,5-己二烯、具有1,5-二烯骨架的1,6-二羰基化合物等多功能有机分子提供新合成方法学.     

钯催化剂催化交叉偶联反应形成P-C键和复杂含磷化合物的研究进展

综述了利用金属钯催化交叉偶联反应形成P-C键以合成各种复杂的含磷化合物特别是手性膦配体的研究进展;介绍了参加偶联反应的不同价态的P化合物亲核试剂,以及卤代烯烃、卤代芳烃、三氟甲磺酸烯基脂、三氟甲磺酸芳基脂、乙烯基硼酸脂等亲电试剂;探讨了相应的偶联反应的反应条件、反应机理及其在材料、医药、农药等领域的应用.     

Studies on the oxidative addition reaction of 1,1-dibromo-1-alkenes, alpha-dehalopalladation, and the intramolecular bis(carbopalladation) reaction of alkenes. An efficient entry to fused bicycles

Twenty-three examples of 1,1-dihalo-1-alkenes were synthesized by the conventional alkylation methods. The oxidative addition reactions of 1,1-dibromo-2,2-diphenylethene or 1, 1-dibromo-2-phenylpropene with a stoichiometric amount of Pd(PPh(3))(4) afforded 1,2-diphenylacetylene and 1-phenylpropyne, respectively, indicating that alpha-dehalopalladation reaction occurred to afford vinylic carbene intermediates. However, alpha-dehalopalladation reaction was not observed in all 1, 1-dihalo-1-alkenes containing an extra C=C bond suitable for cyclic carbopalladation under the current reaction conditions probably due to the fast cyclic carbopalladation reaction of 40A-type of palladium intermediates; A series of bicycles, i.e., fused 5,6-, 6, 6-, 6,7-, and 7,7-bicyclic compounds, were prepared efficiently via this bicyclic carbopalladation protocol. Under condition A, within 0. 5 h, 10 afforded the monocyclic product 37 in 79%. With prolonged reaction time, 37 was converted to bicycle 36. Even with isolated 37, the corresponding reaction under condition A afforded 36 in 92% NMR yield, indicating a stepwise oxidative addition-cyclic carbopalladation-beta-elimination mechanism for this bicyclization reaction.     

A new selective approach to 1,1-bis(silyl)-2-arylethenes and 1,1-bis(silyl)-1,3-butadienes via sequential silylative coupling-Heck coupling reactions

A novel selective route to 1,1-bis(silyl)-1-alkenes has been developed. Sequential one-pot silylative coupling exo-cyclization of 1,2-bis(dimethylvinylsiloxy)ethane followed by the reaction with Grignard reagents leads to the desired 1,1-bis(silyl)ethenes, which are then efficiently coupled in the presence of silver nitrate and palladium acetate with aryl or alkenyl idodides to give the corresponding 1,1-bis(silyl)-2-arylethenes or 1,1,4-trisubstituted 1,3-butadienes with high yield.     

1-trifluoromethylvinylsilane as a CF2=C(-)-CH2+ synthon: synthesis of functionalized 1,1-difluoro-1-alkenes via isolable 2,2-difluorovinylsilanes

Various 1,1-difluoro-1-alkenes such as monosubstituted 1,1-difluoro-1-alkenes, 2-bromo-1,1-difluoro-1-alkenes, and 3,3-difluoroallylic alcohols are synthesized in two simple steps from 1-trifluoromethylvinylsilane: (i) its SN2' reaction with nucleophiles to construct 2,2-difluorovinylsilanes and (ii) the subsequent substitution of electrophiles for the vinylic silyl group. The combination of these two processes allows a one-pot synthesis of the functionalized 1,1-difluoro-1-alkenes starting from 1-trifluoromethylvinylsilane, which functions as a CF2=C(-)-CH2+ synthon.     

A novel synthesis of functionalized 1,1-difluoro-1-alkenes via isolable 2,2-difluorovinylsilanes

Various 1,1-difluoro-1-alkenes such as monosubstituted 1,1-difluoro-1-alkenes, 2-bromo-1,1-difluoro-1-alkenes, and 1,1-difluoro-3-hydroxy-1-alkenes are prepared in two simple steps from 1-trifluoromethylvinylsilane: (i) its S_N2′ reaction with nucleophiles to construct 2,2-difluorovinylsilanes and (ii) the subsequent substitution of electrophiles for the vinylic silyl group.     

Highly selective synthesis of (E)-3-methyl-1-trialkylsilyl-3-en-1-ynes via trans-selective alkynylation catalyzed by Cl2Pd(DPEphos) and stereospecific methylation with methylzincs catalyzed by Pd(tBu3P)2

[reaction: see text] trans-Selective (>or=98%) monoalkynylation of 1,1-dibromo-1-alkenes and 1,1-dichloro-1-alkenes catalyzed by Cl(2)Pd(DPEphos) followed by stereospecific methylation with Me(2)Zn or MeZnX (X= Cl or Br) catalyzed by Pd((t)()Bu(3)P)(2) provides an efficient and stereoselective (>or=98%) route to 5, convertible to a wide variety of enynes and conjugated dienes. In the cases of 1,1-dibromo-1-alkenes, the Sonogashira alkynylation may also be satisfactory, but it is distinctly less satisfactory than the alkynylzinc reaction in cases where 1,1-dichloro-1-alkenes are used.     

One-pot synthesis of telluroketene acetals and haloketene acetals using sp2 geminated hetero organobismetallic intermediates

A novel one-pot synthesis of 1,1-dihalo-1-alkenes and 1,1-bis(butyltelluro)-1-alkenes was developed from hydrozirconation of alkynylzinc bromide with Cp₂Zr(H)Cl and subsequent capture of the Zn/Zr 1,1-heterodimetallo-1-alkene intermediates with halogen and tellurium electrophiles. These protocols, which include multiple reactions in a one-pot procedure, allow the preparation of the potentially useful haloketene acetals and telluroketene acetals from terminal alkynes, under mild conditions and in a good yield.     

3,3-二{2,2-二[4-(N,N-二取代氨基)苯基]乙烯基}-4,5,6,7-四氯-2-苯并[c]呋喃酮的合成

在对甲苯磺酸存在下，采用1,1-二[4-(N,N-二取代氨基)苯基]乙烯(3)和四氯苯酐在乙酸酐溶液中的缩合反应合成了3,3-二{2,2-二[4-(N,N-二取代氨基)苯基]乙烯基}-4,5,6,7-四氯-2-苯并[c]呋喃酮(4)，产率89～93%。3由4,4'-二(N,N-二取代氨基)二苯甲酮(1)与甲基碘化镁进行Grignard反应的产物经水解再脱水制得，产率85%～88.5%(以1为基准)。     

Synthesis of conjugated enediynes via palladium catalyzed cross-coupling reactions of potassium alkynyltrifluoroborates

An efficient synthesis of cross-conjugated enediynes has been developed utilizing the palladium catalyzed cross-coupling reactions of 1,1-dibromo-1-alkenes with potassium alkynyltrifluoroborates under mild conditions.     

New efficient approach to 2,2-diaryl-1,1-difluoro-1-alkenes and 1,1-difluoro-2-aryl-1,3-dienes via Suzuki coupling of alpha-halo-beta,beta-difluorostyrenes

[reaction: see text] Alpha-halo-beta,beta-difluorostyrenes [ArCX = CF2; X = Br, I; Ar = aryl, heteroaryl; synthesized by the Pd(0)-catalyzed coupling reaction of the corresponding alpha-halo-beta,beta-difluoroethenylzinc reagents (CF2=CXZnCl, X = Br, I) with aryl iodides] were functionalized at the halogen site with arylboronic acids under Pd(0)-catalyzed Suzuki-Miyaura coupling reaction conditions to obtain 2,2-diaryl-1,1-difluoro-1-alkenes (ArAr'C=CF2, Ar' = aryl, heteroaryl) in 51-91% isolated yield. The corresponding reaction with alkenylboronic acids produced 1,1-difluoro-2-aryl-1,3-dienes in 53-80% isolated yield. Alternatively, 2,2-disubstituted-1,1-difluoro-1-alkenes were synthesized in moderate yield by a zinc-insertion reaction at the halogen site of the alpha-halo-beta,beta-difluorostyrenes, followed by Pd(0)-catalyzed cross-coupling of the zinc reagent with aryl or alkenyl iodides.     

β,β-二氯丁烯酮甲基上的反应

通过4,4-二氯-3-丁烯-2-酮的氯甲基化,Mannich反应和醇醛缩合制备了1,1,5-三氯-p-戊烯-3-酮(2),1,1-二氯-9-二乙胺基-1-戊烯-3-酮盐酸盐(3)和1,1-二氯-1,4-己二烯-3-酮(4).氯甲基化产品(2)与三乙胺在醚反应生成1,1-二氯-1,4-戊二烯-3-酮(6),在醇中生成1,1-二氯-5-乙氧基-1-戊烯-3-酮(6).与容易在室温中聚合.(2)和氨在醇中反应可得到环化产品N-(4-酮基-5H,6H-2-吡啶基)-3H,4H,5H-吡啶-2,4-二酮.