Regioselective Synthesis Of Indoles Research Articles

Regiodivergent Control in the Gold(I) Catalyzed Synthesis of 7‐Pyrazolylindoles from 1‐Propargyl‐1H‐benzotriazoles and Ynamides through α‐Imino Gold(I) Carbene Complexes

AbstractA smooth, gold catalyzed, atom‐economical and regioselective synthesis of indoles is reported here. The reaction occurs from a nucleophilic attack of in situ synthesized triazapentalenes to gold activated ynamides and involves the participation of α‐imino gold carbene complexes. The use of sulfonyl ynamides drives the reaction to the formation of 2‐amidosubstituted indoles. However, the employment of 2‐oxazolidinolylynamides allows the formation of both isomers, such as, 2‐amido‐ and 3‐amidosubstituted indoles. In this case, the regioselection could be controlled by a correct choice of the catalyst ligand and the electron‐donating capability of the aryl substituent of the ynamide. A correct control in both parameters permits a totally regioselective synthesis of one or the other regioisomer. Isolation of key intermediates and X‐ray analysis allowed for a plausible explanation for this behavior.magnified image

Recent Advances in the Regioselective Synthesis of Indoles via C–H Activation/Functionalization

Indole is an important heterocyclic motif that occurs ubiquitously in bioactive natural products and pharmaceuticals. Immense efforts have been devoted to the synthesis of indoles starting from the Fisher indole synthesis to the recently developed C–H activation/functionalization-based methods. Herein, we have reviewed the progress made on the regioselective synthesis of functionalized indoles, including 2-substituted, 3-substituted and 2,3-disusbstituted indoles, since the year 2010.1 Introduction2 Metal-Catalyzed Synthesis of 2-Substituted Indoles3 Metal-Catalyzed Synthesis of 3-Substituted Indoles4 Metal-Free Synthesis of 3-Substituted Indoles5 Metal-Catalyzed 2,3-Disubstituted Indole Synthesis5.1 Metal-Catalyzed Intramolecular 2,3-Disubstituted Indole Synthesis5.2 Metal-Catalyzed Intermolecular 2,3-Disubstituted Indole Synthesis6 Metal-Free 2,3-Disubstituted Indole Synthesis6.1 N-Protected 2,3-Disubstituted Indole Synthesis6.2 N-Unprotected 2,3-Disubstituted Indole Synthesis7 Applications8 Summary and Outlook

Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides

AbstractMetal carbenes can undergo a myriad of synthetic transformations. Sulfur ylides are potential safe precursors of metal carbenes. Herein, we report cascade reactions that involve carbenoids derived from sulfoxonium ylides for the efficient and regioselective synthesis of indoles and pyrroles. The tandem action of iridium and Brønsted acid catalysts enables rapid assembly of the heterocycles from unmodified anilines or readily accessible enamines under microwave irradiation. The key mechanistic steps are the catalytic transformation of the sulfoxonium ylide into an iridium–carbene complex, followed by N−H or C−H functionalization of an aniline or enamine, respectively, and a final acid‐catalyzed cyclization. The present method was successfully applied to the synthesis of the densely functionalized pyrrole subunit of atorvastatin.

Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides.

Metal carbenes can undergo a myriad of synthetic transformations. Sulfur ylides are potential safe precursors of metal carbenes. Herein, we report cascade reactions that involve carbenoids derived from sulfoxonium ylides for the efficient and regioselective synthesis of indoles and pyrroles. The tandem action of iridium and Brønsted acid catalysts enables rapid assembly of the heterocycles from unmodified anilines or readily accessible enamines under microwave irradiation. The key mechanistic steps are the catalytic transformation of the sulfoxonium ylide into an iridium-carbene complex, followed by N-H or C-H functionalization of an aniline or enamine, respectively, and a final acid-catalyzed cyclization. The present method was successfully applied to the synthesis of the densely functionalized pyrrole subunit of atorvastatin.

Frontispiece: Photoinduced Copper‐Catalyzed Regioselective Synthesis of Indoles: Three‐Component Coupling of Arylamines, Terminal Alkynes, and Quinones

Frontispiece: Photoinduced Copper‐Catalyzed Regioselective Synthesis of Indoles: Three‐Component Coupling of Arylamines, Terminal Alkynes, and Quinones

Photoinduced Copper-Catalyzed Regioselective Synthesis of Indoles: Three-Component Coupling of Arylamines, Terminal Alkynes, and Quinones.

The first successful example of a visible-light-induced copper-catalyzed process for C-H annulation of arylamines with terminal alkynes and benzoquinone is described. This three-component reaction allows use of a variety of commercial terminal alkynes as coupling partners for the one-step regioselective synthesis of functionalized indoles. Moreover, the current process represents a sustainable and atom-economical approach for the preparation of complex indoles from easily accessible starting materials under visible-light irradiation, without the need for expensive metals and harsh reaction conditions.

Photoinduced Copper‐Catalyzed Regioselective Synthesis of Indoles: Three‐Component Coupling of Arylamines, Terminal Alkynes, and Quinones

AbstractThe first successful example of a visible‐light‐induced copper‐catalyzed process for CH annulation of arylamines with terminal alkynes and benzoquinone is described. This three‐component reaction allows use of a variety of commercial terminal alkynes as coupling partners for the one‐step regioselective synthesis of functionalized indoles. Moreover, the current process represents a sustainable and atom‐economical approach for the preparation of complex indoles from easily accessible starting materials under visible‐light irradiation, without the need for expensive metals and harsh reaction conditions.

ChemInform Abstract: Regioselective Synthesis of Indoles via Rhodium‐Catalyzed C—H Activation Directed by an in‐situ Generated Redox‐Neutral Group.

AbstractThe highly regioselective synthesis of unprotected indoles involves the reaction of the hydrochloride substrates with diethyl ketone to form hydrazones.

Regioselective Synthesis of Indoles via Rhodium‐Catalyzed CH Activation Directed by an In‐Situ Generated Redox‐Neutral Group

AbstractA regioselective synthesis of indoles from arylhydrazine hydrochlorides with alkynes and diethyl ketone catalyzed by a rhodium complex is described. A possible mechanism involving an in‐situ generated oxidizing directing group NNCR1R2 assisted ortho‐CH activation and reductive elimination are proposed. The catalytic reaction is highly compatible with a wide range of functional arylhydrazines and alkynes. The reaction proceeds under mild reaction conditions and is atom‐step economical.magnified image

Titanium Reagents in Heterocyclic Synthesis

This review confronts the diversity and selectivity of titanium reagents that mediate heterocyclic synthesis. Applications of different titanium based reagents in various organic reactions leading to the formation of heterocyclic compounds are discussed. Among others, epoxide-opening arene annulations, intramolecular coupling of carbonyl groups intermolecular hydroamination, intramolecular aza-Heck, regioselective synthesis of indoles, anti-Markovnikov hydration of internal and terminal alkynes, and the synthesis of polyarylpyrroles under microwave conditions, are reviewed.

ChemInform Abstract: Regioselective Synthesis of Indoles via Reductive Annulation of Nitrosoaromatics with Alkynes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Regioselective synthesis of indoles via reductive annulation of nitrosoaromatics with alkynes.

[reaction: see text] Indoles are produced regioselectively and in moderate yields by two new processes: (a) from the [CpRu(CO)2]2-catalyzed reaction of nitrosoaromatics (ArNO) with alkynes under carbon monoxide and (b) in a two-step sequence involving the (uncatalyzed) reaction of ArNO with alkynes, followed by reduction of the intermediate adduct.