三价铑催化亚甲胺内盐与丙烯酰胺氧化合成三取代吡唑

将三价铑离子配合物用于催化甲亚胺内盐与取代的丙烯酰胺之间的氧化偶联反应,实现了三取代的吡唑化合物的合成.在这个过程中,取代的丙烯酰胺的烯烃发生了C-H键活化.此类反应和用丙烯酸酯时的反应具有不同的选择性.     

铜催化苯硼酸与苯并呋咱-1-氧化物的胺化反应

C-N键普遍存在于药物和有机功能分子中,传统构建C-N键的方法包括Goldberg反应、Buchwald-Hartwig偶联、Chan-Lam偶联和C-H键活化胺化.虽然这些方法都可以高效构建C-N键,但它们需要使用官能化的芳基底物、官能化的胺化试剂或在氧化条件下进行.理想的胺化反应应在氧化还原中性条件下进行,更为理想的则是在引入氨基的同时引入另外一个官能团.实现这个目标最直接的策略就是使用氮杂环,通过N-E(E=N或O)键的断裂,N原子和E原子可同时被引入.最近我们课题组利用氨茴内酐和氮杂苯并降冰片烯的C-H键活化反应成功实现了这种双官能团化.尽管该法很有吸引力,但是要通过氮杂环的断裂实现双官能团化,需要发生非张力环的开环,这在热力学上是非常不利的.苯并呋咱-1-氧化物可以开环得到邻二硝基苯中间体.基于对胺化反应的兴趣,我们推测苯并呋咱1-氧化物可以作为一个胺化试剂实现苯硼酸的胺化.尽管亚硝基苯对芳基硼酸进行简单的胺化已经被报道,但需要化学计量的铜盐,或是引入还原剂.因此本文报道铜催化的苯硼酸的胺化反应,该反应以苯并呋咱1-氧化物为胺化试剂,在温和及氧化还原中性条件下成功实现了双官能团化.本文共完成了31个不同官能团取代的硝基苯胺骨架结构的合成,反应均以中等到良好的收率得到目标产物,最高收率可达99%.为了增加反应的实用性,我们还进行了放大实验,实验表明,当苯并呋咱-1-氧化物的量由0.2 mmol放大至4 mmol时,反应仍能以较高的收率得到目标产物.此外,目标产物通过进一步的衍生化反应还可方便地转化为其他杂环类化合物.例如,在PPh3作用下,通过还原环化作用可生成吩嗪.在钯催化下可发生分子内碳氢键氧化反应得到咔唑类化合物.通过还原及重氮化反应还可方便地转化为苯并三唑.总之,我们以苯并呋咱-1-氧化物为胺化试剂,在铜催化下成功实现了苯硼酸的胺化反应,合成了一系列双官能团化产物.该催化体系反应条件温和,底物适用范围广,对各种官能团具有很好的兼容性.     

Cu2O/1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide catalyzed C-N cross-coupling reaction in aqueous media

An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of imidazole, indole, pyrrole, alkyl alcohol amines, and alkyl amines with aryl iodides and bromides. The reaction proceeds in water-ethanol media at 120 °C for 12 h with Cu₂O as the catalyst, 1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide (L2) as the ligand, NaOH as the base to generate a wide range of N-arylated products in moderate to excellent yields. Aqueous medium, ease of operation, and broad substrate scope give the process a benign environmental profile.     

Synthesis of PI3K inhibitor GDC-0077 via a stereocontrolled N-arylation of α-amino acids

An efficient synthesis of PI3K inhibitor GDC-0077, featuring two consecutive Cu-catalyzed CN coupling reactions, is reported. The described synthetic route involves a chemoselective Ullmann-type coupling of a chiral difluoromethyl-substituted oxazolidinone, a Cu-catalyzed N-arylation of l-alanine with high stereochemical integrity, and a high-yielding final amide bond formation step to produce GDC-0077 in >99.5 area % HPLC purity.     

Base-free anaerobic Cu(II) catalysed aryl-nitrogen bond formations

The coupling of arylboronic acids with imidazole in the presence of binuclear bis-μ-hydroxy copper(II) complexes is reported. The reactions can be performed in air as well as under nitrogen atmosphere. Reactions are carried out at ambient temperature without the need for base. The presence of water is essential for the reaction to proceed. Ligand effects on the yield and selectivity are reported.     

蚕丝蛋白辅助铜催化碳氮偶联反应

采用碘化亚铜/蚕丝蛋白催化体系催化芳基卤代物与咪唑之间发生偶联反应, 高收率得到了多种N-芳基化产物. 本文方法不仅可实现产物的克级规模制备, 还可用于2-苯基吲哚和三氮唑的合成. 此外, 提出了该催化体系下的反应机理.     

水相铜/十二烷基取代酰肼-吡啶-N-氧化物催化咪唑的N-芳基化

设计合成了5种新型烷基取代酰肼-吡啶-N-氧化物,并将其作为水相铜催化含氮杂环与芳香碘代物偶联反应的配体.实验结果表明,十二烷基取代酰肼-吡啶-N-氧化物的催化效果最佳.对影响反应的其它条件,如铜源、碱、反应时间和温度等条件进行了优化,建立了最佳反应条件:CuO(10%,摩尔分数),NaOH(1 mmol),TBAB(5%,摩尔分数),L5(20%,摩尔分数),于120℃反应12 h,无需惰性气体保护.在此条件下,芳香碘代物与咪唑偶联反应的产率为60%~92%.该方法的特点是以水作为反应溶剂,长链烷基取代酰肼-吡啶-N-氧化物同时起到了铜催化剂配体和相转移催化剂的作用.     

One-Pot Synthesis of α-Methyl Vinyl Sulfones From Ethyl Phenyl Sulfones

Various α-methyl vinyl sulfones were synthesized by Homer-Emmons olefination of aldehydes and sulfonyl phosphonate generated from 1,1-dilithiosulfone.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Pd-catalyzed C-N coupling of primary (het)arylamines with 5-substituted 3-chloro-4H-1,2,6-thiadiazin-4-ones

The Buchwald-Hartwig Pd-catalyzed C-N coupling reaction of 5-substituted 3-chloro-4H-1,2,6-thiadiazin-4-ones with primary (het)arylamines is described, affording twenty new 3,5-disubstituted 4H-1,2,6-thiadiazin-4-ones in 56–99% yield. The protocol enables the mild preparation of difficult to access 3,5-dianilino-1,2,6-4H-thiadiazin-4-ones. The reaction scope and limitations are discussed.