铜催化N′-芳基苯磺酰肼的N′-芳基化反应

以N′-芳基苯磺酰肼作为芳基化试剂,在铜催化下,实现N′-芳基苯磺酰肼的自身N-芳基化反应。该反应以5 mol%的醋酸铜为催化剂,三乙胺为碱,甲醇为溶剂,常温下N′-芳基苯磺酰肼反应4~8 h,产率最高可达88%。产物结构经^1H NMR,^13C NMR和HR-MS(ESI)表征。     

铜促进的8-酰氨基喹啉类化合物N-芳基化反应

研究了铜促进的8-酰氨基喹啉类化合物的N-芳基化反应.在40 mol%Cu(OAc)_2,2.0 equiv.NaHCO_3作用下,1,4-二氧六环为溶剂,100℃下,8-酰氨基喹啉与三芳基铋发生N-芳基化反应,以中等至较高产率得到目标产物.该反应具有良好的底物普适性,为N-芳基酰胺类化合物的合成提供了一种新的方法.     

铁催化烯基芳烃的氢芳基化、甲基芳基化和二芳基化制备非对称1,1-二芳基烷烃的反应（英文）

报道了一种新型的铁催化的烯基芳烃的氢芳基化、甲基芳基化和双芳基化的反应.富电子的苯甲醚以及1,3,5-三甲氧基苯在温和条件下和烯基芳烃反应得到非对称的1,1-二芳基烷烃.其中,在氢芳基化反应中,苯甲酰基过氧化物被用作氧化剂;在甲基芳基化和双芳基化反应中,叔丁基过氧酯是氧化剂.     

2-炔基苯胺与二芳基碘鎓盐的选择性芳基化/环化串联反应

有机高价碘试剂是一类环境友好、制备简单且性质温和的有机合成新试剂。近年来,有机高价碘试剂因表现出新颖、独特的反应性能而受到化学工作者广泛关注,成为有机合成重要研究领域之一。二芳基碘鎓盐是有机高价碘试剂的一个重要组成部分,是一类具有较高普适性的芳基化试剂,可用于羰基化合物、烯烃、炔烃和杂原子亲核化合物等的芳基化反应。目前,二芳基碘鎓盐作为芳基化试剂对具有单一芳基化位点化合物的芳基化已经有了非常广泛而深入的研究。对于具有两个甚至多个芳基化位点的化合物(如同时具有胺基和炔基),其芳基化选择性问题仍缺乏系统研究。特别是在多个芳基化位点共存时如何能够使芳基化发生在某一特定位点仍然是一大难题。这限制了二芳基碘鎓盐作为芳基化试剂更广泛的应用。因此,我们选用2-炔基苯胺(含有胺基和炔基两个芳基化位点)作为原料,通过溶剂的选择以及溶液酸碱性的调控来改变不同芳基化位点的反应活性,通过催化剂的调变来改变二芳基碘鎓盐芳基化反应的能力,从而找出最优条件实现底物分子的选择性芳基化反应,并利用剩余活性位点实现分子内的环化反应,从而实现芳基化-环化串联反应合成一系列N-芳基吲哚类化合物。在对模型底物进行条件筛选实验时发现,以2-乙基辛酸铜(Cu(OCOC8H17)2)作催化剂,二异丙基乙基胺(DIPEA)作碱,1,2-二氯乙烷(DCE)为溶剂,反应以最高93%的收率得到1,2-二苯基吲哚。使用该最优反应条件,一系列2-炔基苯胺都能与二芳基碘鎓盐很好地发生反应并且以良好到优秀的产率(71%–98%)得到目标产物N-芳基吲哚。此外,2-炔基苯胺与非对称的二芳基碘鎓盐也能发生反应,实验结果证明为位阻较小的芳基对胺基进行了N-芳基化反应。通过空白实验和对比实验,我们提出了可能的反应机理：二芳基碘鎓盐在铜催化剂作用下转化为亲电性的芳基活性中间体,该中间体与底物的胺基发生芳基化反应,然后芳基化产物在铜催化剂作用下环化生成N-芳基吲哚。该反应很好地解决了同时具有胺基和炔基两个芳基化位点的底物与二芳基碘鎓盐反应时C-芳基化和N-芳基化的竞争问题,选择合适反应条件使N-芳基化反应优先进行,为二芳基碘鎓盐的选择性芳基化反应提供了很好的实例,并为其它具有多个芳基化位点化合物的选择性芳基化反应提供了途径。     

2-炔基苯胺与二芳基碘鎓盐的选择性芳基化/环化串联反应（英文）

有机高价碘试剂是一类环境友好、制备简单且性质温和的有机合成新试剂.近年来,有机高价碘试剂因表现出新颖、独特的反应性能而受到化学工作者广泛关注,成为有机合成重要研究领域之一.二芳基碘鎓盐是有机高价碘试剂的一个重要组成部分,是一类具有较高普适性的芳基化试剂,可用于羰基化合物、烯烃、炔烃和杂原子亲核化合物等的芳基化反应.目前,二芳基碘鎓盐作为芳基化试剂对具有单一芳基化位点化合物的芳基化已经有了非常广泛而深入的研究.对于具有两个甚至多个芳基化位点的化合物(如同时具有胺基和炔基),其芳基化选择性问题仍缺乏系统研究.特别是在多个芳基化位点共存时如何能够使芳基化发生在某一特定位点仍然是一大难题.这限制了二芳基碘鎓盐作为芳基化试剂更广泛的应用.因此,我们选用2-炔基苯胺(含有胺基和炔基两个芳基化位点)作为原料,通过溶剂的选择以及溶液酸碱性的调控来改变不同芳基化位点的反应活性,通过催化剂的调变来改变二芳基碘鎓盐芳基化反应的能力,从而找出最优条件实现底物分子的选择性芳基化反应,并利用剩余活性位点实现分子内的环化反应,从而实现芳基化-环化串联反应合成一系列N-芳基吲哚类化合物.在对模型底物进行条件筛选实验时发现,以2-乙基辛酸铜(Cu(OCOC8H17)2)作催化剂,二异丙基乙基胺(DIPEA)作碱,1,2-二氯乙烷(DCE)为溶剂,反应以最高93%的收率得到1,2-二苯基吲哚.使用该最优反应条件,一系列2-炔基苯胺都能与二芳基碘鎓盐很好地发生反应并且以良好到优秀的产率(71%–98%)得到目标产物N-芳基吲哚.此外,2-炔基苯胺与非对称的二芳基碘鎓盐也能发生反应,实验结果证明为位阻较小的芳基对胺基进行了N-芳基化反应.通过空白实验和对比实验,我们提出了可能的反应机理:二芳基碘鎓盐在铜催化剂作用下转化为亲电性的芳基活性中间体,该中间体与底物的胺基发生芳基化反应,然后芳基化产物在铜催化剂作用下环化生成N-芳基吲哚.该反应很好地解决了同时具有胺基和炔基两个芳基化位点的底物与二芳基碘鎓盐反应时C-芳基化和N-芳基化的竞争问题,选择合适反应条件使N-芳基化反应优先进行,为二芳基碘鎓盐的选择性芳基化反应提供了很好的实例,并为其它具有多个芳基化位点化合物的选择性芳基化反应提供了途径.     

1-苯基-2-丙酮的合成新方法

以苯胺为原料,经重氮化反应和改进的Meerwein芳基化反应合成了1-苯基-2-丙酮(2)。优化的Meer-wein芳基化反应条件为:醋酸异丙烯酯为溶剂,氧化亚铜为催化剂,n(氟硼酸重氮盐)∶n(氧化亚铜)=10∶1,反应温度35℃~40℃,反应时间6 h。在优化反应条件下,2的收率达91%。     

MK-287类PAF拮抗剂的合成

以(±)-4,10-二氧杂三环[5,2,1,0^2,6]-癸-8-烯-3-醇和PhTi(OPr-i)₃为原料,经过芳基化、氧化、芳基化、环化、热分解和加氢反应,高立体选择性地合成了反式-2,5-二芳基四氢呋喃.     

电化学条件下富电子芳烃的C—H官能团化实现烯烃的1,2-二芳基化

传统的烯烃二芳基化主要手段是,先通过过渡金属催化的芳基亲电试剂与烯烃发生交叉偶联,然后再与芳基亲核试剂发生反应[1].但是这种反应策略存在原子经济性低及反应步骤多的缺点.因此急需发展一种高效、高原子经济性的合成方法来实现烯烃的二芳基化.2015年,Bunel/Lei课题组[2]报道了FeCl3/2,3-二氯-5,6-二氰基对苯醌(DDQ)催化条件下苯乙烯的1,2-二芳基化;2017年,Bao课题组[3]报道了Fe(OTf)3/DDQ催化条件下苯乙烯的1,2-二芳基化。     

大位阻、富电子MOP型烷基膦配体在钯催化的1,3-二羰基化合物 α-芳基化反应中的应用

富电子、大位阻MOP型烷基膦配体2-二叔丁基膦-2’-异丙氧基-1,1’-联萘(L1)在钯催化的1,3-二羰基化合物的α-芳基化反应中显示了较好的催化活性. 在这类催化反应中, 碱的选择具有重要的影响: 以K3PO4为碱, Pd(OAc)2/L1催化体系在丙二酸二乙酯的α-芳基化中, 富电子溴代芳烃显示较好的活性; Pd(OAc)2/L1催化的乙酰乙酸乙酯α-芳基化时, 以 K2CO3为碱, 催化体系显示较好的活性, 这个催化体系可控制反应得到α-芳基乙酰乙酸乙酯, 而不是脱乙酰基的产物. 较为惰性的氯代芳烃在Pd(OAc)2/L1的催化下, 也能够跟1,3-二羰基化合物发生α-芳基化反应.     

通过(E)-7-甲基-2,6-辛二烯酸的立体选择性Mizoroki-Heck芳基化反应合成(E)-3-芳基-7-甲基-2,6-辛二烯酸（英文）

对Pd(OAc)_2和P(o-MeC_6H_4)_3催化的(E)-7-甲基-2,6-辛二烯酸与碘代芳烃的立体选择性Mizoroki-Heck芳基化反应进行了优化,在减少催化剂的用量以及过量的三乙胺同时作碱和溶剂的条件下,产物的收率得到了显著的改善.在回流温度下通过Mizoroki-Heck芳基化反应,以37%～68%的分离收率合成了20个(E)-3-芳基-7-甲基-2,6-辛二烯酸,它们的结构经过IR, ~1H NMR, ~(13)C NMR, HR-ESI-MS和X射线衍射的表征.     

Microwave-assisted Pd(OH)2-catalyzed direct C−H arylation of free-(NH2) adenines with aryl halides

A direct C−H arylation of free-(NH₂) adenines using Pd(OH)₂/C (Pearlman’s catalyst) and stoichiometric amount of copper iodide under ligandless microwave activation is described. This new protocol proved to be highly effective to synthesize a variety of 8-aryladenine derivatives 3 without prior protection of the amino substituent. The arylation reaction takes place rapidly within few minutes and allows the coupling to proceed regioselectively at the 8-position with a wide range of aryl halides including aryl iodides, bromides and the less reactive aryl chlorides.     

Aryliodine (III) Diacetates as Substrates for Pd-Ag Catalyzed Arylation of Alkenes

An unprecedented application of aryliodine(III) diacetates as substrates in Pd-Ag catalyzed arylation of alkenes is described. The mechanistic studies revealed that the binary Pd-Ag catalysis leads to the decomposition of aryliodine(III) diacetates to oxygen and aryl iodides followed by arylation of alkenes forming Heck-type products. Under optimized conditions both electron-rich and electron-deficient alkenes undergo arylation in high yields. Advantageously, the reaction proceeds smoothly in water as a solvent and neither organic ligands nor inert atmosphere are required.     

Rh(I)-catalyzed arylation of heterocycles via C-H bond activation: expanded scope through mechanistic insight

A practical, functional group tolerant method for the Rh-catalyzed direct arylation of a variety of pharmaceutically important azoles with aryl bromides is described. Many of the successful azole and aryl bromide coupling partners are not compatible with methods for the direct arylation of heterocycles using Pd(0) or Cu(I) catalysts. The readily prepared, low molecular weight ligand, Z-1-tert-butyl-2,3,6,7-tetrahydrophosphepine, which coordinates to Rh in a bidentate P-olefin fashion to provide a highly active yet thermally stable arylation catalyst, is essential to the success of this method. By using the tetrafluoroborate salt of the corresponding phosphonium, the reactions can be assembled outside of a glovebox without purification of reagents or solvent. The reactions are also conducted in THF or dioxane, which greatly simplifies product isolation relative to most other methods for direct arylation of azoles employing high-boiling amide solvents. The reactions are performed with heating in a microwave reactor to obtain excellent product yields in 2 h.     

Palladium-catalyzed direct arylation of heteroaromatic compounds: improved conditions utilizing controlled microwave heating

A versatile and rapid microwave-assisted procedure for the palladium-catalyzed direct arylation of heterocycles by aryl bromides and heteroaryl bromides is described. This novel protocol features short coupling times (10-60 min) and low catalyst loadings (1 mol %) and allows the successful arylation of previously unreactive heterocyclic substrates.     

Regioselective palladium-catalyzed phenylation of ethyl 4-oxazolecarboxylate

The efficient and regioselective palladium-catalyzed C-2 arylation of ethyl 4-oxazolecarboxylate 1 with phenyliodide is described. The different parameters (solvent, base, ligand and catalyst) for the optimal conditions of this arylation process have been screened.     

Diastereoselective addition of arylzinc reagents to sugar aldehydes

The diastereoselective arylation of sugar-derived aldehydes is described. The arylating reagents are generated in situ by a boron-to-zinc exchange reaction of arylboronic acids with Et(2)Zn to generate arylethylzinc reagents. The exquisite reactivity of the arylzinc reagents allowed for an efficient and mild arylation, delivering the corresponding products in diastereoisomeric ratios of up to >20:1. The utility of the methodology is highlighted with an efficient formal synthesis of (+)-7-epi-goniofufurone, a member of the styryllactone family of natural products.     

Direct arylation of imidazo[2,1‐b]thiazoles and thiazoles with aryl iodides via CuCl2/PPh3‐catalyzed C–H bond functionalization

With PPh₃ acting as a ligand, a convenient method for CuCl₂‐catalyzed arylation of imidazo[1,2‐b]thiazoles and thiazoles with aryl iodides under mild reaction conditions is described. Preliminary mechanistic studies of this arylation involving a formal Cu(I) to Cu(0) and Cu(II) route by convergent disproportionation of the copper mediator are also reported. Copyright © 2015 John Wiley & Sons, Ltd.     

Palladium-catalyzed rearrangement/arylation of 2-allyloxypyridine leading to the synthesis of N-substituted 2-pyridones

[reaction: see text] The Pd-catalyzed one-pot rearrangement/arylation of 2-allyloxypyridine is described. The catalyst/base combination of Pd[P(t-Bu)(3)](2)/Ag(2)CO(3) was found to be optimal for this one-pot rearrangement/arylation. The initial rearrangement of 2-allyloxypyridine was found to be catalyzed by both Pd(0) and Pd(II) complexes with different mechanisms.     

Copper-mediated C-H bond arylation of arenes with arylboronic acids

A new copper-mediated cross-coupling of arenes and arylboronic acids is described. Under the influence of Cu(OCOCF 3) 2, the C-H bond arylation of electron-rich arenes with arylboronic acids takes place to afford a range of biaryls in good yields. The reaction is selective for cross-coupling; no homocoupling product arising from arenes or arylboronic acids is detected. Multiple C-H bond arylation is possible with indoles and pyrroles furnishing interesting extended pi-systems.