Copper-Catalyzed Radical Enantioselective Synthesis of γ-Butyrolactones with Two Non-vicinal Carbon Stereocenters.

Chiral heterocycles with two or more carbon stereocenters are quite important skeletons in many fields. However, powerful strategies for the construction of such synthetically valuable heterocycles, especially with two or more remote carbon stereocenters, have largely lagged behind. We report here a powerful method for the synthesis of chiral γ-butyrolactones with two non-vicinal carbon stereocenters from readily available chemical feedstocks under mild conditions. Both of the two diastereoisomers can be obtained with good to excellent enantioselectivities. The well-designed copper/PyBox catalytic system overrides the intrinsic stereoinduction of the close chirality center generated by the previous innocent radical addition step. Nevertheless, this work has the power to selectively provide one single diastereoisomer by taking advantage of the epimerization effect but also to synthesize all four diastereoisomers with the pair of chiral ligands L2 and L2' having opposite chirality. The obtained useful chiral γ-butyrolactones can be synthetically transformed into acyclic or cyclic molecules with two non-vicinal carbon stereocenters. Mechanistic studies reveal that this radical reaction follows a linear relationship and can be well performed with a less loading amount of ligand compared to that of the copper catalyst.

Synthesis of unsymmetrically tetrasubstituted pyrroles and studies of AIEE in pyrrolo[1,2-a]pyrimidine derivatives.

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-a]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-a]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

Electrochemical fluoromethylation triggered lactonizations of alkenes under semi-aqueous conditions.

An electrochemical difluoromethylation triggered lactonization of alkenes was developed for the first time. This protocol employs readily prepared CF2HSO2Na as the difluoromethylating reagent, affording unprecedented CF2H-containing lactones in moderate yields. Moreover, with CF3SO2Na as the trifluoromethylating reagent, a wide array of CF3-containing lactones were obtained under additional supporting electrolyte- and catalyst-free conditions.

Electrochemical Hofmann rearrangement mediated by NaBr: practical access to bioactive carbamates.

An electrochemical Hofmann rearrangement is reported. With the mediation of NaBr, highly corrosive and toxic halogens are avoided. Moreover, this efficient and green approach is well compatible with a broad range of amides, including several commercial medicine derivatives, and provides direct access to synthetically useful carbamates. The synthetic utility of this method is also demonstrated by the preparation of 15N labeling carbamate and gram-scale synthesis of Amantadine.

Electrochemical Formation of N-Acyloxy Amidyl Radicals and Their Application: Regioselective Intramolecular Amination of sp2 and sp3 C-H Bonds.

Electrochemical generation of N-acyloxy amidyl radicals via an inner-sphere electron-transfer process is described for the first time. With NaBr as the catalyst and electrolyte, the in situ generated amidyl radicals undergo intramolecular C(sp2/sp3)-H aminations to give lactams with unprecedented regio- and chemoselectivities. Moreover, the synthetic utility of current method is demonstrated by the synthesis of PJ34 and Phenaglaydon.

Electrocatalytic Dehydrogenative Esterification of Aliphatic Carboxylic Acids: Access to Bioactive Lactones.

A scalable and efficient electrocatalytic dehydrogenative esterification is reported. With an indirect electrolysis strategy, both intra- and intermolecular-type reactions were amenable to this practical method. With n-Bu4NI as the catalyst, undesired decarboxylation and Baeyer-Villiger oxidation were suppressed. More importantly, this novel method provided reliable and direct access to the natural product cytosporanone A on a gram scale.