p-Toluenesulfonic acid-promoted organic transformations for the generation of molecular complexity.

Since the beginning of this century, p-toluenesulfonic acid (p-TSA) catalysed organic transformations have been an active area of research for developing efficient synthetic methodologies. Often, catalysis using p-TSA is associated with many advantages, such as operational simplicity, high selectivity, excellent yields, and ease of product isolation, which make organic synthesis convenient and versatile. Notably, p-TSA is a non-toxic, commercially available, inexpensive solid organic compound that is soluble in water, alcohols, and other polar organic solvents. p-TSA is a strong acid compared to many protic or mineral acids and its high acidity helps activate different organic functional groups. p-TSA-promoted conversions are fast, have a high atom and pot economy, and feature a multiple bond-forming index. Therefore, the utilization of p-TSA enables the synthesis of many important structural scaffolds without any hazardous metals, making it desirable in numerous applications of sustainable and green chemistry. Recently, this emerging area of research has become one of the pillars of synthetic organic chemistry to synthesise biologically relevant, complex carbocycles and heterocycles. This study provides a comprehensive summary of methods, applications, and mechanistic insights into p-TSA-catalysed organic transformations, covering the literature reports that have appeared since 2012.

Oxidative Addition to the N-C Bond Vs Formation of the Zwitterionic Intermediate in Platinum(II)-Catalyzed Intramolecular Annulation of Alkynes to Form Indoles: Mechanistic Studies and Reaction Scope.

In this study, Pt(II)-catalyzed intramolecular translocation annulation of ortho-alkynylamides to the formation of indoles is presented, where a proposed intermediacy of zwitterionic intermediate has been substantiated over the oxidative addition. We focused our attention on Pt(II)-catalyzed aminoacylation of alkynes both theoretically and experimentally using low boiling solvent where the formation of deacylation product was suppressed simultaneously. One-step intramolecular [1,3]-acyl migration from the zwitterionic intermediate is highly unlikely, which imparts a high energy barrier of +99.0 kcal mol-1. Another possible approach involving oxidative addition to the N-C bond, migratory insertion to alkyne, and subsequent reductive elimination is also explored through DFT studies to justify the reaction consequence. However, based on the computational studies, it is suggested that initial zwitterion formation is highly favored over oxidative addition. We suggest the formation of an acylium intermediate, which can further react with indol-3-ylplatinum species in an intramolecular manner, albeit within the same solvent cage to form 3-acyl indoles.

Water extract of red mud: an efficient and renewable medium for environmentally benign synthesis of 2-amino-4H-chromenes.

In this study, an efficient and convenient domino Michael addition/intramolecular cyclization protocol is presented for the synthesis of biologically relevant 2-amino-4H-chromenes in short reaction times using water extract of red mud (WERM) at room temperature. Red mud is generated abundantly as wastes in aluminum industries and this is the first report to utilize WERM as an effective and renewable medium in organic synthesis. As the precursor material is a waste, the present method is environmentally benign and economical. The final 2-amino-4H-chromenes were obtained in high yields by simple precipitation and subsequent washing by aqueous ethanol which eliminates the chromatographic separation. The present method is tolerated by electronically diverse functional groups and also applicable for large-scale synthesis. Moreover, WERM was recovered from the reaction medium and reused for several cycles without significant loss of reactivity.

Gold-catalyzed formal cycloaddition of 2-ethynylbenzyl ethers with organic oxides and α-diazoesters.

A world of possibilities: Gold-catalyzed reactions of 2-ethynylbenzyl ethers with organic oxides and α-diazoesters gave 1,3-dihydroisobenzofuran and naphthalene derivatives, respectively (see scheme; EWG = electron-withdrawing group). Mechanisms for the formation of the formal cycloadducts were elucidated by isotope labeling.

Platinum-catalyzed oxoarylations of ynamides with nitrones.

A new platinum-catalyzed oxoarylation of ynamides with nitrones is reported. Cascade sequences for the synthesis of indolin-2-ones via NaBH(3)CN reduction in situ of the initially formed oxoarylation products are also developed.

Intermolecular gold-catalyzed diastereo- and enantioselective [2+2+3] cycloadditions of 1,6-enynes with nitrones.

Going for gold: The title reaction has been developed and demonstrates a wide substrate scope with respect to the 1,6-enynes and nitrones (see scheme; DCE = 1,2-dichloroethane, Tf = trifluoromethanesulfonyl). The results for the enantioselective versions are also presented.

Gold-catalyzed 1,2-difunctionalizations of aminoalkynes using only N- and O-containing oxidants.

We report two viable routes for the 1,2-difunctionalization of aminoalkynes using only oxidants. In the presence of a gold catalyst, nitrones enable the oxoamination of aminoalkynes 1 to form 2-aminoamides 2. With a suitable gold catalyst, nitrosobenzenes implement an alkyne/nitroso metathesis of the same substrates to give 2-oxoiminylamides 3. These two novel oxidations also provide 1,2-aminoalcohols with opposite regioselectivity via NaBH(4) reduction in situ.

Gold-catalyzed stereoselective synthesis of azacyclic compounds through a redox/[2 + 2 + 1] cycloaddition cascade of nitroalkyne substrates.

We report a new redox/cycloaddition cascade on readily available 1-alkynyl-2-nitrobenzenes that produces complex azacyclic compounds stereoselectively. The core structures of the resulting products are constructed through a formal [2 + 2 + 1] cycloaddition among α-carbonyl carbenoids, nitroso species, and external alkenes.

The skeletal rearrangement of gold- and platinum-catalyzed cycloisomerization of cis-4,6-dien-1-yn-3-ols: pinacol rearrangement and formation of bicyclo[4.1.0]heptenone and reorganized styrene derivatives.

With gold and platinum catalysts, cis-4,6-dien-1-yn-3-ols undergo cycloisomerizations that enable structural reorganization of cyclized products chemoselectively. The AuCl3-catalyzed cyclizations of 6-substituted cis-4,6-dien-1-yn-3-ols proceeded via a 6-exo-dig pathway to give allyl cations, which subsequently undergo a pinacol rearrangement to produce reorganized cyclopentenyl aldehyde products. Using chiral alcohol substrates, such cyclizations proceed with reasonable chirality transfer. In the PtCl2-catalyzed cyclization of 7,7-disubstituted cis-4,6-dien-1-yn-3-ols, we obtained exclusively either bicyclo[4.1.0]heptenones or reorganized styrene products with varied substrate structures. On the basis of the chemoselectivity/structure relationship, we propose that bicyclo[4.1.0]heptenone products result from 6-endo-dig cyclization, whereas reorganized styrene products are derived from the 5-exo-dig pathway. This proposed mechanism is supported by theoretic calculations.