Sudhir K. Sharma

Cascade intermolecular Michael addition-intramolecular azide/internal alkyne 1,3-dipolar cycloaddition reaction in one pot.

A rapid one-pot protocol for the synthesis of indole-based polyheterocycles via a sequential Lewis acid catalyzed intermolecular Michael addition and an intramolecular azide/internal alkyne 1,3-dipolar cycloaddition reaction has been described. The generality of the method has been demonstrated by treating a series of aromatic/aliphatic 2-alkynyl indoles with substituted (E)-1-azido-2-(2-nitrovinyl)benzenes to furnish annulated tetracyclic indolo[2,3-c][1,2,3]triazolo[1,5-a][1]benzazepines in good yields.

Synthesis of Iodo-Indoloazepinones in an Iodine-Mediated Three-Component Domino Reaction via a Regioselective 7-endo-dig Iodo-Cyclization Pathway±CDRI Communication No. 8094

An efficient and rapid synthetic strategy for the naturally occurring indoloazepinone scaffold via a three-component reaction of indole-2-carboxamides, 1,3-disubstituted propargyl alcohols, and I(2) is described. The strategy involves a C-H functionalization-alkyne activation-intramolecular hydroamidation-deprotonation domino sequence. The salient feature of this sequence is regioselective electrophilic 7-endo-dig iodo-cyclization during the intramolecular hydroamidation to afford a seven-membered azepinone ring annulated to the indole.

Unprecedented Cu-Catalyzed Coupling of Internal 1,3-Diynes with Azides: One-Pot Tandem Cyclizations Involving 1,3-Dipolar Cycloaddition and Carbocyclization Furnishing Naphthotriazoles†

A one-pot protocol for the synthesis of triazole-annulated polyheterocycles via metal-catalyzed coupling of internal 1,4-disubstituted 1,3-diynes and organic azides has been described. The mechanistic rationale for the reaction suggests tandem cyclizations involving copper-catalyzed cycloaddition and 6-endo carbocyclization reactions. The cascade cyclization leads to an increase in molecular complexity to furnish naphtho[1,2-d]triazoles in satisfactory yields. The generality of the method has been demonstrated by using a series of aromatic/aliphatic azides and symmetrical internal 1,3-diynes.

Pictet-Spengler Reaction Revisited: Engineering of Tetherd Biheterocycles into Annulated Polyheterocycles

This micro review focuses on the application of the modified Pictet-Spengler reaction to the synthesis of diverse polyheterocy- cles with structural resemblance to natural products. The modified Pictet-Spengler reaction takes use of tethered biheterocycles compris- ing nucleophilic partner and a source for electrophilic partner followed by their condensation with aldehydes/ketones to furnish annulated polyheterocycles. Using this strategy engineering of numerous tethered biheterocycles into annulated polyheterocycles has been success- fully carried out using both 6-endo as well as 7-endo cyclizations.

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

Summary A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields.

Temperature-Gradient-Directed NMR Monitoring of a [3 + 3]-Cyclocondensation Reaction Between Alkynone and Ethyl 2-Amino-1H-indole-3-carboxylate Toward the Synthesis of Pyrimido[1,2-a]indole Catalyzed by Cs2CO3

Abstract We describe a NMR strategy to resolve temperature-gradient-monitored real-time chemical reaction involving a [3 + 3]-cyclocondensation reaction between alkynone and ethyl 2-amino-1H-indole-3-carboxylate toward the synthesis of pyrimido[1,2-a]indole catalyzed by Cs2CO3. The in situ NMR study clearly indicates that the reactant undergoes [3 + 3]-cyclocondensation reaction through a concerted mechanism, resulting in the product formation. The detailed NMR spectroscopic data led to the optimization of the reaction conditions and quantitative analysis of the product accurately and efficiently. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT