Diversity-Oriented Synthesis of Aliphatic Fluorides via Reductive C(sp3 )-C(sp3 ) Cross-Coupling Fluoroalkylation.

Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel-catalyzed monofluoromethylation of unactivated alkyl halides using a low-cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross-coupling of two alkyl halides. Results with 1-bromo-1-fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3 )-C(sp3 ) cross-coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional-group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first-order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate-determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.

Diverse Synthesis of Chiral Trifluoromethylated Alkanes via Nickel-Catalyzed Asymmetric Reductive Cross-Coupling Fluoroalkylation.

The trifluoromethyl group represents one of the most functional and widely used fluoroalkyl groups in drug design and screening, while the drug candidates containing chiral trifluoromethyl-bearing carbons are still few due to the lack of efficient methods for the asymmetric introduction of trifluoromethyl group into organic molecules. Herein, we described a nickel-catalyzed asymmetric trifluoroalkylation of aryl iodides, for the first time, by utilizing reductive cross-coupling in enantioselective fluoroalkylation. This novel method has demonstrated high efficiency, mild conditions, and excellent functional group tolerance, especially for substrates containing diverse pharmaceutical and bioactive molecules moieties. This strategy provided an efficient and facile way for diversity-oriented synthesis of chiral trifluoromethylated alkanes.

A fast-responsive two-photon fluorescent probe for monitoring endogenous HClO with a large turn-on signal and its application in zebrafish imaging.

A novel fast-responsive two-photon fluorescent probe NS-ClO was constructed for imaging endogenous HClO in living cells, tissues and fresh zebrafish with a large turn-on signal (about 860 times) and Stokes shift (about 90 nm). The probe NS-ClO for the recognition of HClO in vivo exhibited fast response (about 1 min) and good selectivity; thus, it might be a useful tool to understand the role of HClO in various physiological processes.