咔唑及其衍生物合成方法研究进展

咔唑及其衍生物是一类重要的含氮芳杂环化合物,具有许多独特的理化性质及生物活性,分析、归纳、总结了近5年来发表的文献,选取具有代表性的实例,并按照中间体的不同将合成方法分为四类,分别讨论了咔唑及其衍生物合成方法的进展情况,对咔唑及其衍生物成环的新方法给予重点关注.     

基于多米诺反应合成吲哚衍生物

近年来,多米诺反应作为合成吲哚衍生物的有效方法已得到有机合成化学家的广泛关注.该反应过程中,不需改变反应条件和添加试剂,中间体也无需分离和提纯,实现了原子经济和环境友好的目标.通过过渡金属催化的多米诺反应合成吲哚衍生物,已经得到了深入研究并成为一种构筑该类杂环的有利工具.重点综述了近年来运用金属催化多米诺反应合成吲哚及其衍生物方面的研究进展,以催化剂的类型进行分类,介绍相关反应的特点和优势.     

3-取代吲哚衍生物的合成

目前吲哚化学的研究是杂环化学中最活跃的领域之一,特别是3-取代吲哚衍生物,已用于许多天然产物和相应具有生物活性化合物重要骨架的构筑,其合成方法的研究格外令人注目。近年来,由吲哚一步合成3-取代吲哚衍生物的报道剧增。本文按合成过程中所用催化剂的种类,综述近几年来由吲哚为原料一步合成二吲哚甲烷、β-吲哚酮、β-吲哚醇、β-吲哚硝基化合物和α-吲哚甲胺等为代表3-取代吲哚衍生物的研究进展。     

5-取代吲哚类化合物的合成

5－取代吲哚类化合物是一种重要的医药中间体。从古典的Fischer方法开始，有关合成5－取代吲哚类化合物的方法不断出现。本文对各种合成方法进行了介绍和评价。参考文献30篇。     

合成3,3''''-二吲哚基苯基甲烷的新方法

以无水乙醚为溶剂,室温下无水三氯化铝催化N-(2-氯乙基)苯甲醛亚胺与吲哚反应,合成了3,3'-二吲哚基苯基甲烷和6,12-二苯基吲哚[2,3-b]咔唑,其结构经1H NMR,IR和MS表征.     

N-乙基咔唑甲酰化衍生物的合成

以咔唑为原料,经烷基化和甲酰化反应合成了3-甲酰基-N-乙基咔唑和3,6-二甲酰基-N-乙基咔唑,其结构经1H NMR, IR和MS表征.重点研究了反应条件对甲酰化反应的影响.研究结果表明,甲酰化反应的较适宜条件为: 1 10 mmol, n(DMF) : n(1)=10 : 1, 1,2-二氯乙烷(25 mL)为溶剂,回流反应8 h～48 h.通过选择适当的反应条件,可以提高产率以及控制单乙酰化和双乙酰化产物的选择性.     

合成3,3′-二吲哚基苯基甲烷的新方法

以无水乙醚为溶剂,室温下无水三氯化铝催化N-(2-氯乙基)苯甲醛亚胺与吲哚反应,合成了3,3′-二吲哚基苯基甲烷和6,12-二苯基吲哚[2,3-b]咔唑,其结构经1HNMR,IR和MS表征。     

咔唑双乙酰化衍生物的合成及其电子光谱

以咔唑为原料,通过SN1亲核取代和Friedel-Crafts亲电取代反应合成了咔唑双乙酰化衍生物——3,6-二乙酰基-N-乙基咔唑和3,6-二乙酰基-N-丁基咔唑,其结构经1H NMR,IR,MS和元素分析表征,并讨论了它们的电子吸收光谱。     

烯烃叠氮化和芳基化合成吲哚啉酮衍生物

以廉价、易得的N-烷基-N-芳基甲基丙烯酰胺衍生物为起始原料,叠氮化钠为叠氮源,碘苯二乙酸为氧化剂,1,2-二氯乙烷为溶剂,合成了吲哚啉酮衍生物。该反应经历了无过渡金属催化烯烃的芳基化和叠氮化。目标化合物结构经¹H NMR,¹³C NMR和MS(ESI)表征。     

新型吲哚衍生物的合成及其光学性质

以吲哚为原料,经Vilsmeier-Haack, Ullmannhe和Witting-Hornor反应合成了两个新型的含吲哚环共轭化合物--1,4-二(3-苯乙烯基吲哚基)苯（4a）和1,4-二(3-萘乙烯基吲哚基)苯（4b）,其结构经¹H NMR, ¹³C NMR, IR和ESI-MS表征。光学性能研究结果表明,4a和4b的λ_max分别位于330 nm和348 nm;在330 nm波长激发下,λ_em分别位于410 nm和425 nm。     

Carbazoles from the [4C+2C] Reaction of 2,3‐Allenols with Indoles

A mild and efficient method using readily available 1‐aryl‐2,3‐allenols and unprotected‐N indoles, Au⁺‐catalyzed cyclization, and aromatization to afford the final [4C+2C] products, carbazoles 4, with an excellent selectivity, is reported. The reaction demonstrates excellent regioselectivity and allows the N?H unit to undergo reactivity unprotected. A mechanism involving a spiropolycyclic intermediate has been proposed and synthetic application is also demonstrated.     

IrIII‐Catalyzed One‐Pot Cascade Synthesis of Pentacyclic‐Fused Carbazoles from Indoles and Diazoes

A highly efficient Ir^III‐catalyzed cascade cyclization of indoles and diazoes giving access to unique pentacyclic‐fused carbazoles has been developed. This novel strategy expanded the application scope of coupling partners to take diazo compounds as a C2 source, and two new cycles, three new C?C and one new C?N bonds were formed in one‐pot.     

Aqueous Titanium Trichloride Promoted Reductive Cyclization of o‐Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

Treatment of o‐nitrostyrenes with aqueous TiCl₃ solution at room temperature afforded indoles through a formal reductive C(sp²)–H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From β,β‐disubstituted o‐nitrostyrenes, 2,3‐disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine.     

Synthesis of Diterpene Indoles from Cyclopentenonepimaric Acid

Diterpene indoles were prepared by the Fischer reaction from cyclopentenonepimaric acid. The structures of the synthesized compounds were confirmed by IR and NMR spectroscopies.     

Functional Carbazole-Fullerene Complexes: A New Perspective of Carbazoles Acting as Nano-Octopus to Capture Globular Fullerenes

Fullerene host-guest constructs have attracted increasing attention owing to their molecular-level hybrid arrangements. However, the usage of simple carbazolic derivatives to bind with fullerenes is rare. In this research, three novel carbazolic derivatives, containing a tunable bridging linker and carbazole units for the capturing of fullerenes, are rationally designed. Unlike the general concave-convex interactions, fullerenes could interact with the planar carbazole subunits to form 2-dimensional hexagonal/quadrilateral cocrystals with alternating stacking patterns of 1 : 1 or 1 : 2 stoichiometry, as well as the controllable fullerene packing modes. At the meanwhile, good electron-transporting performances and significant photovoltaic effects were realized when a continuous C_60⋅⋅⋅C₆₀ interaction channel existed. The results indicate that the introduction of such carbazolic system into fullerene receptor would provide new insights into novel fullerene host-guest architectures for versatile applications.     

Catalytic Functionalization of Indoles in a New Dimension

140 Years ago Adolf von Baeyer proposed the structure of a heteroaromatic compound which revolutionized organic and medical chemistry: indole. After more than a century, indole itself and the complexity of naturally occurring indole derivatives continue to inspire and influence developments in synthetic chemistry. In particular, the ubiquitous presence of indole rings in pharmaceuticals, agrochemicals, and functional materials are testament to the ever increasing interest in the design of mild and efficient synthetic routes to functionalized indole derivatives. This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C? C bond‐forming processes) over the last four years.     

Regioselective Formation of Substituted Indoles: Formal Synthesis of Lysergic Acid

A Diels–Alder reaction-based strategy for the synthesis of indoles and related heterocycles is reported. An intramolecular cycloaddition of alkyne-tethered 3-aminopyrones gives 4-substituted indolines in good yield and with complete regioselectivity. Additional substitution is readily tolerated in the transformation, allowing synthesis of complex and non-canonical substitution patterns. Oxidative conditions give the corresponding indoles. The strategy also allows the synthesis of carbazoles. The method was showcased in a formal synthesis of lysergic acid.     

Chemoselective N‐Alkylation of Indoles in Aqueous Microdroplets

Many reactions show much faster kinetics in microdroplets than in the bulk phase. Most reported reactions in microdroplets mirror the products found in bulk reactions. However, the unique environment of microdroplets allows different chemistry to occur. In this work, we present the first chemoselective N‐alkylation of indoles in aqueous microdroplets via a three‐component Mannich‐type reaction without using any catalyst. In sharp contrast, bulk reactions using the same reagents with a catalyst yield exclusively C‐alkylation products. The N‐alkylation yield is moderate in microdroplets, up to 53 %. We extended the scope of the microdroplet reaction and obtained a series of new functionalized indole aminals, which are likely to have biological activities. This work clearly indicates that microdroplet reactions can show reactivity quite different from that of bulk‐phase reactions, which holds great potential for developing novel reactivities in microdroplets.     

Regio‐ and Chemoselective N‐1 Acylation of Indoles: Pd‐Catalyzed Domino Cyclization to Afford 1,2‐Fused Tricyclic Indole Scaffolds

A concise method for the synthesis of 1,2‐fused tricyclic indole scaffolds by domino cyclization involving a Pd‐catalyzed Sonogashira coupling, indole cyclization, regio‐ and chemoselective N‐1 acylation, and 1,4‐Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2‐a]indole and hexahydro[1,5]diazocino[1,2‐a]indole scaffolds.