[4+1]Annulation of in situ generated azoalkenes with amines:A powerful approach to access 1-substituted 1,2,3-triazoles

1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially dangerous acetylene and azides.Here we report a base-mediated[4+1]annulation of azoalkenes generated in situ from readily available difluoroacetaldehyde N-tosylhydrazones(DFHZ-Ts)with amines under relatively mild conditions.This azide-and acetylene-free strategy provides facile access to diverse 1-substituted 1,2,3-triazole derivatives in high yield in a regiospecific manner.This transformation has great functional group tolerance and can suit a broad substrate scope.Furthermore,the application of this novel methodology in the gram-scale synthesis of an antibiotic drug PH-027 and in the late-stage derivatization of several bioactive small molecules and clinical drugs demonstrated its generality,practicability and applicability.

Neighbouring carbonyl group-assisted sequential 1,2-azide and1,4-oxygen migrations of vinyl azides leading to α-azido ketones

The development of azide migration reactions is a formidable challenge due to potential competition from side processes driven by the release of molecular nitrogen. Here, we show a novel neighbouring carbonyl group-assisted sequential 1,2-azide and 1,4-oxygen migration reaction of α-vinyl azides for the efficient preparation of a range of α-azido ketones. This represents the first transformation of α-vinyl azides into α-azido ketones. Notable features of this method are its high efficiency, broad substrate scope, excellent functional group compatibility, and high yields. The computational studies gave a key insights into the regioselective 1,2-azide and 1,4-oxygen migrations assisted by the neighbouring carbonyl group. Further conversions into a variety of nitrogen-containing compounds demonstrated the synthetic utility of the α-azido ketone products. Preliminary mechanistic studies disclosed a novel reaction mechanism involving neighbouring carbonyl group-assisted sequential 1,2-azide and1,4-oxygen migrations.

Silver-catalyzed unstrained C(CO)–alkyl bond scission via[3+2]/retro-[3+2]cycloaddition of ketones with N-isocyanoiminotriphenylphosphorane

C(CO)–alkyl bonds are ubiquitous in a variety of organic molecules,and their selective activation and functionalization are important for the reconstruction of simple ketones into valuable building blocks.However,due to the thermodynamic and kinetic stability,the cleavage and transformation of the unstrained C(CO)–alkyl bonds remain a significant challenge.Herein,we report a novel silver-catalyzed scission of the unstrained C(CO)–alkyl bond of ketones by reacting with N-isocyanoiminotriphenylphosphorane(NIITP)under mild conditions.This method could transform a variety of unstrained ketones into iminophosphoranes and nitriles in high yields.Experimental and computational studies disclosed the reaction proceeded through an unprecedented[3+2]/retro-[3+2]cycloaddition mechanism.

Fluoroalkyl N-sulfonyl hydrazones:An efficient reagent for the synthesis of fluoroalkylated compounds

Fluoroalkyl N-sulfonyl hydrazones are versatile reagents that can be used to synthesize a wide range of diverse fluoroalkylated organic molecules.Although it has been known since 1975,the chemistry of fluoroalkyl N-sulfonyl hydrazones has recently only received great attention from the scientific community.Generally,they are used as either safe and bench-stable diazo precursors in carbene transfer reactions or as 1,3-dipoles in cycloaddition and cyclization reactions.Notably,fluoroalkyl N-sulfonyl hydrazones to replace toxic fluoroalkyl diazo compounds in carbene transfer reactions reduce the risk of rapid accumulation of explosive diazo compounds and improve functional group compatibility and substrate scope.Given the growing importance of fluoroalkyl N-sulfonyl hydrazones in chemical synthesis,a comprehensive review of this topic in the literature is essential to demonstrate their synthetic potential.In this review,we critically summarize and comprehensively analyze the publications in various literatures on the chemistry of fluoroalkyl N-sulfonyl hydrazones starting from 1990 to date.The classification of the different reactivity profiles of fluoroalkyl N-sulfonyl hydrazones and the efficiencies of similar types of reactions or substrates with fluoroalkyl diazo compounds are compared.