Catalyst-Free Transfer Hydrogenation of Activated Alkenes Exploiting Isopropanol as the Sole and Traceless Reductant.

Both metal-catalyzed and organocatalytic transfer hydrogenation reactions are widely employed for the reduction of C=O and C=N bonds. However, selective transfer hydrogenation reactions of C=C bonds remain challenging. Therefore, the chemoselective transfer hydrogenation of olefins under mild conditions and in the absence of metal catalysts, using readily available and inexpensive reducing agents (i.e. primary and secondary alcohols), will mark a significant advancement towards the development of green transfer hydrogenation strategies. Described herein is an unconventional catalyst-free transfer hydrogenation reaction of activated alkenes using isopropanol as an eco-friendly reductant and solvent. The reaction gives convenient synthetic access to a wide range of substituted malonic acid half oxyesters (SMAHOs) in moderate to good yields. Mechanistic investigations point towards an unprecedented hydrogen bond-assisted transfer hydrogenation process.

Aza-Quasi-Favorskii Reaction: Construction of Highly Substituted Aziridines through a Concerted Multibond Rearrangement Process.

A new molecular rearrangement, the aza-Quasi-Favorskii rearrangement, has been developed for the construction of highly substituted aziridines. Electron-deficient O-sulfonyl oximes react readily with α,α-disubstituted acetophenone-derived enolates to furnish highly substituted aziridines via this unprecedented domino process. In-depth computational studies reveal an asynchronous yet concerted nitrenoid-type rearrangement pathway.

Imines as acceptors and donors in N-heterocyclic carbene (NHC) organocatalysis.

The synthetic potential of imines as electrophiles or as a source of nucleophilic coupling partner in N-heterocyclic carbene (NHC) catalysis for the synthesis of various nitrogen heterocycles and functionalized amines is highlighted in this Feature Article. Electrophilic imines are suitable candidates for intercepting the NHC-derived acyl anions, homoenolate equivalents, and (di)enolates for the synthesis of α-amino ketones and a variety of lactam derivatives. Moreover, enamines generated from imines bearing α-hydrogen could be trapped with α,ß-unsaturated acylazoliums for the synthesis of functionalized dihydropyridinones. NHCs are also useful for the umpolung of imines for the generation of aza-Breslow intermediates thus leading to the synthesis of indoles, quinolines, dihydroquinoxalines etc. A concise account of the diverse reactivity of imines in NHC catalysis has been presented.

N-Heterocyclic Carbene Catalysis Exploiting Oxidative Imine Umpolung for the Generation of Imidoyl Azoliums.

Although NHC-catalyzed umpolung of imines are known, the related reactions under oxidative conditions are limited. Described herein is the two-step process involving the initial formation of aldimines from the corresponding aldehydes and 2-amino benzyl alcohols followed by NHC-catalyzed cyclization proceeding via the imidoyl azoliums under oxidative conditions. The reaction allowed the synthesis of trifluoromethylated 3,1-benzoxazines in good yields and broad scope. The role of NHC in the intramolecular cyclization and preliminary mechanistic experiments are also provided.

Oxidative NHC Catalysis for the Generation of Imidoyl Azoliums: Synthesis of Benzoxazoles.

N-Heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of aldimines generated from 2-amino phenols and aromatic aldehydes leading to the synthesis of 2-arylbenzoxazoles under mild conditions is presented. The reaction proceeds via the generation of the aza-Breslow intermediates from imines and NHC, which under oxidative conditions form the key imidoyl azoliums and a subsequent intramolecular cyclization furnishes the product. The reaction tolerates a broad range of functional groups, and the products are formed in generally good yields.

Base-Free and Catalyst-Free Synthesis of Functionalized Dihydrobenzoxazoles via Vinylogous Carbonate to Carbamate Rearrangement.

An unexpected, catalyst-free, and base-free intramolecular cyclization of N-aryloxyacrylate aldimines, under thermal conditions leading to the synthesis of functionalized dihydrobenzoxazoles, is reported. The reaction features a unique rearrangement of vinylogous carbonates to vinylogous carbamates resulting in a new carbon-oxygen and carbon-nitrogen bond construction. The reaction tolerates a broad range of functional groups and the desired products are formed in moderate to good yields.

Enantioselective Synthesis of Functionalized ß-Lactones by NHC-Catalyzed Aldol Lactonization of Ketoacids.

N-Heterocyclic carbene (NHC)-catalyzed intramolecular aldol lactonization of readily available ketoacids leading to the enantioselective synthesis of cyclopentane-fused ß-lactones is presented. The reaction proceeds via the generation of NHC-bound enolate intermediates formed from the ketoacids in the presence of the peptide coupling reagent HATU and NHC generated from the chiral triazolium salt. The functionalized ß-lactones are formed under mild conditions in high yields and enantioselectivities.

N-Heterocyclic-Carbene-Catalyzed Umpolung of Imines.

N-Heterocyclic carbene (NHC) catalysis has been widely used for the umpolung of aldehydes, and recently for the umpolung of Michael acceptors. Described herein is the umpolung of aldimines catalyzed by NHCs, and the reaction likely proceeds via aza-Breslow intermediates. The NHC-catalyzed intramolecular cyclization of aldimines bearing a Michael acceptor resulted in the formation of biologically important 2-(hetero)aryl indole 3-acetic-acid derivatives in moderate to good yields. The carbene generated from the bicyclic triazolium salt was found to be efficient for this transformation.