可见光诱导烯烃环化合成二氟烷基化异喹啉二酮

发展了一种可见光诱导的活泼烯烃串联自由基环化合成含氟异喹啉二酮的反应。 在可见光诱导下,多种N-烷基-N-甲基丙烯酰基苯甲酰胺与二氟溴乙酸乙酯发生自由基串联环化反应,以66%~75%的产率合成了一系列具有潜在生理活性的二氟烷基化异喹啉二酮。 此研究为合成具有潜在药用价值的氟取代异喹啉二酮提供了一条高效、条件温和的途径。     

可见光诱导的烯炔和多氟烷基卤环化合成含氟异喹啉酮

发展了一种可见光诱导的1,7-烯炔与全氟烷基卤串联原子转移自由基加成(ATRA)/环化合成含氟2,4-二氢异喹啉-2(1H)-酮的反应。以多氟烷基碘或溴为自由基前体,面式-三( 2-苯基吡啶)合铱(摩尔分数1%)为光敏剂,在5 W蓝光发光二极管(LED)照射下,多种苯桥联1,7-烯炔顺利发生串联(ATRA)/环化反应,以中等到优秀(62%~84%)的产率合成了一系列多氟化异喹啉酮衍生物。 此合成方法反应条件温和、清洁、高效且底物适用范围广,为具有潜在药用价值的多氟化2,4-二氢异喹啉-2(1H)-酮的合成提供新的途径。     

无金属催化烯烃自由基环化合成多氟取代吲哚酮

一种无金属催化的活泼烯烃与全氟碘代丁烷自由基环化合成含氟吲哚酮的反应被发展。 在廉价易得的的偶氮二异丁腈(AIBN)介导下, 多种N-芳基丙烯酰胺类化合物与全氟碘代丁烷发生自由基串联环化反应,以53%~85%的产率合成了一系列的潜在生理活性的多氟取代吲哚酮。 此工作为潜在药用价值的多氟取代吲哚酮合成提供了一条高效、廉价、绿色的新途径。     

铜催化苯甲酰胺有氧环化合成7-叔烷基异喹啉二酮

发展了一种高效、简单的铜/空气催化体系催化的苯甲酰胺串联自由基环化合成7-叔烷基异喹啉二酮的反应。 在廉价CuI存在下,空气环境中,N-烷基-N-甲基丙烯酰基苯甲酰胺与AIBN发生串联自由基加成/环化/碳碳偶联反应,以52%~73%的产率合成了一系列的7-取代异喹啉二酮。 此研究为合成具有潜在药用价值的含氰取代异喹啉二酮提供了一条快速、简单、温和的构建途径。     

多氟烷基取代的环丙烷衍生物的合成

以连二亚硫酸钠为引发剂, 烯丙基丙二酸二乙酯与多氟烷基碘代烷在温和反应条件下反应, 方便地得到一系列多氟烷基取代的环丙烷衍生物, 产率45%～55%. 在相同条件下, 烯丙基乙酰乙酸乙酯与多氟烷基碘代烷反应得到相应的加成物, 加成物随后用碱处理也得到环合的产物.     

铜催化苯甲酰胺与烷基偶氮试剂环化合成含α-取代季碳中心异喹啉二酮

发展了一种苯甲酰胺自由基自由基环化制备α-官能化叔烷基取代的异喹啉二酮的新反应。此环化反应以偶氮试剂为α-取代叔烷基自由基源物质,利用碘化亚铜/空气体系催化N-烷基-N-甲基丙烯酰基苯甲酰胺发生环化,经过串联自由基加成/环化/碳-碳键形成过程,一步构建了三重碳-碳键,以41%~71%的产率合成了一系列异喹啉二酮及其衍生物。特别值得提出得是,此研究发展了一种新型α-官能叔烷基自由基源物质,发现了一种同时引入两个α-官能叔烷基片段的串联新反应。反应底物适应范围广,反应高效,催化体系廉价实用,为具有潜在药用价值的含α-取代季碳中心的异喹啉二酮及衍生物的合成提供了一条廉价、简单、快捷的新途径。     

氟烷基取代的双酚A类衍生物的合成

利用相转移催化剂十六烷基三甲基溴化铵(CTMAB)催化的连二亚硫酸钠引发的苯酚衍生物与含氟碘代烷的氟烷基化反应, 合成了含氟烷基取代的酚类化合物. 研究了双酚A与含氟碘代烷的氟烷基化反应, 得到了一类重要的含氟单体, 即含氟烷基取代的双酚A衍生物. 通过改变含氟碘代烷与双酚A的摩尔比, 可以得到单取代、二取代和四取代的含氟烷基双酚A衍生物.     

可见光促进的自由基型三重键插入反应在多取代芳(杂)环合成中的应用

综述了本课题组近年来在利用可见光促进的自由基型三重键插入反应合成多取代芳香化合物方面的研究进展.使用异腈插入反应构建了邻位取代吡啶、1-位取代异喹啉和6-位取代的菲啶衍生物;使用炔烃插入反应合成了多取代的萘酚和呋喃及异喹啉酮衍生物;还利用异腈/炔烃的多米诺插入反应构建了喹啉衍生物和异腈/氰基的多米诺插入反应构建了喹喔啉衍生物.这些反应都是在可见光促进的光氧化还原条件下进行,反应条件温和,产率较高.     

铜催化苯甲酰亚胺高烯丙酯的分子内胺化全氟烷基化反应

报道了铜催化苯甲酰亚胺高烯丙酯底物的分子内胺化全氟烷基化反应. 该反应以全氟碘代烷为全氟烷基化试剂, 醋酸铜为催化剂, 邻菲啰啉为配体, 在醋酸银存在下以中等的收率实现苯甲酰亚胺高烯丙酯底物末端双键的胺化全氟烷基化, 最终生成1,3-噁嗪类分子. 多种官能团取代的苯甲酰亚胺高烯丙酯和具有不同碳链长度的全氟碘代烷烃都能适用于该反应, 为多氟烷基取代的1,3-噁嗪类化合物的合成提供了一种简洁的方法. 多氟烷基取代的1,3-噁嗪类化合物还可在温和条件下高效转化为γ氨基醇衍生物. 初步的机理研究证明该反应经历了全氟烷基自由基对碳碳双键的亲电加成, 之后苯甲酰亚胺基团作为分子内亲核性胺源经历分子内亲核取代途径生成1,3-噁嗪骨架.     

可见光诱导的共轭磺酰胺串联脱砜/环化反应

发展了一种可见光诱导的共轭磺酰胺串联脱砜/环化,合成全氟烷基化吲哚酮或α-芳基酰胺的方法。此反应以多氟烷基碘或溴为氟源,在发光二极管蓝光灯照射下,利用面式-三(2-苯基吡啶)合铱催化N-烷基-N-甲基丙烯酰基苯磺酰胺经过串联自由基加成/β-芳基迁移/脱砜环化过程,一步构筑两重碳-碳键,以41%~78%的产率合成了一系列含氟吲哚酮或α-芳基酰胺。此方法底物适用范围广,反应条件温和(室温),催化体系绿色,为具有潜在生理活性的含氟吲哚酮及α-芳基酰胺的合成提供了一条高效、快捷的新途径。     

Cascade radical cyclization/cross-coupling of halobenzamides by synergistic Cu/Fe catalysis: An access to 7-tert-alkylated isoquinolinediones

A Cu/Fe-cocatalyzed cyclization of halobenzamides with azo reagents involving regioselective radical/radical cross-coupling toward functionalized isoquinolinediones was developed. Applying azo reagents as the coupling partner, in the presence of cheap, facile and ligand-free catalytic combination of CuI/Fe(NH₄)₂(SO₄)₂·6H₂O/air, the halobenzamide radicals generated by a prior radical addition/cyclization process underwent radical/radical cross-coupling via the cleavage of C-X (X?=?F, Cl, Br, I, OMe, OBn) bond with excellent site selectivity, leading to a series of isoquinolinediones furnished dual distal α-functional quaternary moieties. In addition, the theoretical calculation on the C-X bond cleavage and the positional selectivity using unrestricted density functional theory (DFT) was also conducted.     

Metal-free visible-light-promoted thiocyanation/cyclization cascade for the synthesis of thiocyanato-containing isoquinolinediones

A visible-light induced metal-free thiocyanate radical addition/intramolecular cyclization cascade reaction for the synthesis of thiocyanato-containing isoquinolinediones from N-alkyl-N-methacryloylbenzamides is described. The organic dye 9-mesityl-10-methylacridinium perchlorate (Acr⁺-Mes ClO₄⁻) is used as a photocatalyst, and cheap and readily available ammonium thiocyanate is used to provide thiocyanate radical by single-electron transfer pathway. The reaction completes the synthesis of CS and CC bonds in one pot with abundant molecular oxygen as the sole sacrificial reagent. The method is easy to implement, and 25 new compounds have been prepared in moderate to good yields under mild conditions. This is the first time that a thiocyanate group has been introduced into isoquinoline-1,3(2H,4H)-diones to construct highly functional drug-like molecules.     

Alkyl radical cyclization to vinylogous carbonates for the stereoselective synthesis of unsymmetrical dioxa-cage compounds: effect of conformation on the rate of cyclization versus reduction

An efficient strategy for the stereoselective construction of unsymmetrical dioxa-cage compounds containing ether linkages employing a 6-exo-trig alkyl radical cyclization to vinylogous carbonates is developed. The radical precursors are prepared from the diols obtained from the Diels-Alder adducts via iodoetherification followed by addition of the alcohol to the ethyl propiolate. The geometrical constrains play important role in deciding the outcome of the reaction as cyclization versus simple reduction. Formation of the mono-oxa-cage compounds via a 5-exo-trig intramolecular alkyl radical cyclization to olefin is also described. The dioxa-cages could also be assembled employing a tandem oxymercuration reduction-radical cyclization to vinylogous carbonates protocol with equal efficiency and with reduced number of steps.     

Visible-light-induced dearomative spirocyclization of N-benzylacrylamides toward perfluorinated azaspirocyclic cyclohexadienones

A feasible approach to 2-azaspirocyclic cyclohexadienones via visible-light-induced perfluoroalkylation cyclization of N-benzylacrylamides was reported. Using R_f-X (X = I or Br) as the R_f radical source, the reaction underwent a cascade radical addition/dearomative cyclization process by Ir photocatalyst, leading to various 2-azaspiro[4.5]deca-6,9-diene-3,8-diones bearing perfluorinated groups including CF₃, n-C₃F₇, n-C₄F₉, n-C₆F₁₃, n-C₈F₁₇, n-C₁₀F₂₁, CH₂CF₂ and CF₂CO₂Et.     

An unusual transformation of perfluorinated 1- and 3-phenylpropenes to polyfluorochloroindanes by the action of AlCl3

The reaction of perfluorinated 1- and 3-phenylpropenes with AlCl₃ gives polyfluorochloroindanes as the result of an intramolecular cyclization, apparently, by an electrophilic pathway.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2854–2857, December, 1989.     

Synthesis of nitrogen-containing heterocycles using exo- and endo-selective radical cyclizations onto enamides

The effect of positional change of the carbonyl group of enamides on Bu₃SnH-mediated alkyl radical cyclization leading to five-, six-, seven-, and eight-membered nitrogen-containing heterocycles was examined. A 5-exo cyclization is generally preferred over a 6-endo ring closure in systems having an alkyl radical center on the enamide-acyl side chain, whereas enamides having an alkyl radical center opposite to the acyl side chain predominantly gave 6-endo cyclization products. These results suggest that the exo or endo selectivity of radical cyclization onto the alkenic bond of enamides can be controlled by positional change of the carbonyl group. For an understanding of these selectivities, heat of formation for each transition state was calculated. 6-endo-Selective radical cyclization was applied to the radical cascade, enabling a concise synthesis of a cylindricine skeleton. A 7- or 8-endo alkyl radical cyclization, however, predominated over a corresponding 6- or 7-exo ring closure regardless of the positional change of the carbonyl group of enamides.