Direct Transformation of Terminal Alkynes into Amidines by a Silver-Catalyzed Four-Component Reaction.

An unprecedented conversion of terminal alkynes into N-sulfonimidamides (amidines) is reported by a silver-catalyzed, one-pot, four-component reaction with TMSN3, sodium sulfinate, and sulfonyl azide. The reaction scope includes both aromatic and aliphatic alkynes. A possible cascade reaction mechanism, consisting of alkyne hydroazidation, sulfonyl radical addition, 1,3-dipolar cycloaddition by TMSN3, and retro-1,3-dipolar cycloaddition, is proposed. TMSN3 is found to play an essential role in each step of the reaction.

BODIPY-Labeled Cyclobutanes by Secondary C(sp3 )-H Arylations for Live-Cell Imaging.

Arylated cyclobutanes were accessed by a versatile palladium-catalyzed secondary C(sp3 )-H activation, exploiting chelation assistance by modular triazoles. The C-H arylation led to cyclobutane natural product derivatives in a highly regioselective fashion, setting the stage for the easy access to novel fluorogenic boron-dipyrrin (BODIPY)-labeled probes for live-cell imaging.

Expedient Access to 2-Benzazepines by Palladium-Catalyzed C-H Activation: Identification of a Unique Hsp90 Inhibitor Scaffold.

Bioactive 2-benzazepines were accessed in an atom- and step-economical manner through a versatile palladium-catalyzed C-H activation strategy. The C-H arylation required low catalyst loading and a mild base, which was reflected by a broad scope and high functional-group tolerance. The benzotriazolodiazepinones were identified as new heat shock protein 90 (Hsp90) inhibiting lead compounds, with considerable potential for anti-cancer applications.

Use of trifluoroacetaldehyde N-tfsylhydrazone as a trifluorodiazoethane surrogate and its synthetic applications.

Trifluorodiazoethane (CF3CHN2), a highly reactive fluoroalkylating reagent, offers a useful means to introduce trifluoromethyl groups into organic molecules. At present, CF3CHN2 can only be generated by oxidation of trifluoroethylamine hydrochloride under acidic conditions; due to its toxic and explosive nature, its safe generation and use remains a prominent concern, hampering wider synthetic exploitation. Here we report the development of trifluoroacetaldehyde N-tfsylhydrazone (TFHZ-Tfs) as a CF3CHN2 surrogate, which is capable of generating CF3CHN2 in situ under basic conditions. The reaction conditions employed in this chemistry enabled a difluoroalkenylation of X-H bonds (X = N, O, S, Se), affording a wide range of heteroatom-substituted gem-difluoroalkenes, along with Doyle-Kirmse rearrangements and trifluoromethylcyclopropanation reactions, with superior outcomes to approaches using pre-formed CF3CHN2. Given the importance of generally applicable fluorination methodologies, the use of TFHZ-Tfs thus creates opportunities across organic and medicinal chemistry, by enabling the wider exploration of the reactivity of trifluorodiazoethane.

Silver-Catalyzed Regio- and Stereoselective Formal Carbene Insertion into Unstrained C-C σ-Bonds of 1,3-Dicarbonyls.

A regio- and stereoselective silver-catalyzed formal carbene insertion into 1,3-dicarbonyls has been developed, using N-nosylhydrazones as diazo surrogates. Two new C-C bonds are constructed at the carbenic carbon center through the selective cleavage of the C-C(=O) σ-bond of acyclic 1,3-dicarbonyls, enabling the preparation of various synthetically useful polysubstituted γ-diketones, γ-ketoesters, and γ-ketoamides in high yields. The in situ formation of a donor-acceptor cyclopropane, via reaction of the enolate of the 1,3-dicarbonyl with an electrophilic silver carbenoid, is proposed as a key process in the catalytic cycle.