This critical review discusses recent developments in the field of cyclopropene chemistry. Although several excellent reviews that mainly focused on the thermolysis and pyrolysis as well as metal-mediated reactions of cyclopropenes have been published, significant new developments have also been achieved in recent years. This brand new review provides an overview of the progress from 2007 to 2011 on the syntheses and transformations of cyclopropenes as well as their related mechanistic studies (238 references).

Recent developments of cyclopropene chemistry.

This review covers the addition of diazo compounds to ketones to afford homologated ketones, either in the presence or in the absence of promoters or catalysts. Reactions with diazoalkanes, aryldiazomethanes, trimethylsilyldiazomethane, α-diazo esters, and disubstituted diazo compounds are covered, commenting on the complex regiochemistry of the reaction and the nature of the catalysts and promoters. The recent reports on the enantioselective version of ketone homologation reactions are gathered in one section, followed by reports on the use of cyclic ketones ring expansion in total synthesis. Although the first reports of this reaction appeared in the literature almost one century ago, the recent achievements, in particular, for the asymmetric version, forecast the development of new breakthroughs in the synthetically valuable field of diazo chemistry.

Homologation Reaction of Ketones with Diazo Compounds

Ketenes and Other Cumulenes as Reactive Intermediates

Progress in 1,3-dipolar cycloadditions in the recent decade: an update to strategic development towards the arsenal of organic synthesis

Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. To elevate the reactivities of cyclooctynes, two strategies, LUMO lowering through propargylic fluorination and strain enhancement through fused aryl rings, have been explored. Here we report the facile synthesis of a difluorobenzocyclooctyne (DIFBO) that combines these modifications. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. However, we were able to trap DIFBO by forming a stable inclusion complex with β-cyclodextrin in aqueous media. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. Using this procedure, we found that the rate constant for the cycloaddition reaction of DIFBO with an azide exceeds those for difluorinated cyclooctyne (DIFO) and dibenzocyclooctyne (DIBO). Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry.

http://pubs.acs.org/doi/pdf/10.1021/ja105005t

Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by β-Cyclodextrin

Teaching new tricks to an old dog: By intercepting adducts between ketones and lithium trimethylsilyldiazomethane, a new Tiffeneau-Demjanov type methylene homologation could be realized in a single-step operation. Among proton sources and Lewis acids, silica gel was found to be the most effective reagent for the protonation of intermediates and their subsequent ring expansion (see scheme).

New Methylene Homologation Method for Cyclic Ketones

A novel transition-metal-catalyzed rearrangement of silylated cyclopropenes to the corresponding allenes is described. The presence of both the trimethylsilyl group on the cyclopropene and the platinum catalyst are crucial for this rearrangement.

Metal-Catalyzed Rearrangement of Cyclopropenes to Allenes

Regioselectivity of alkylidene carbene-mediated C−H insertion was explored utilizing electronic, conformational, steric, and stereoelectronic effects. Relying on these factors, highly regio- and chemoselective carbene insertion reaction of C−H bonds in different environments could be obtained. The observed selectivity clearly indicates that an electronic effect plays a more important role than steric effect. In general, C−H bonds in conformationally rigid cyclic environments are less reactive than those in acyclic systems toward carbene insertion, and in this situation, a competing intermolecular reaction between alkylidene carbene and trimethylsilyldiazomethane led to the formation of allenylsilanes. The formation of allenylsilane becomes more favorable as the concentration of reaction becomes higher, as well as the C−H bonds undergoing insertion becomes electronically and conformationally deactivated.

Selectivity control in alkylidene carbene-mediated C-H insertion and allene formation.

A new cyclopropanation reaction involving Cα−Si bond insertion of alkylidene carbenes derived from α-silyl ketones has been developed. This unprecedented alkylidene carbene reactivity features excellent selectivity for insertion into Cα−Si bonds rather than insertion into Cγ−H bonds or addition to γ,δ-double or -triple bonds. The selectivity trend clearly indicates that the α-oxygen in the tether significantly promotes Cγ−H insertion, although the Cα−Si bond insertion still competes effectively.

Chunrui Sun

Papers

New Methylene Homologation Method for Cyclic Ketones

Metal-Catalyzed Rearrangement of Cyclopropenes to Allenes

Selectivity control in alkylidene carbene-mediated C-H insertion and allene formation.

Cyclopropenation of Alkylidene Carbenes Derived from α-Silyl Ketones

Sequential reactions of trimethylsilyldiazomethane with 4-alkenyl ketones and aldehydes catalyzed by lewis bases