Copper-catalyzed silylation of cyclopropenes using (trifluoromethyl)trimethylsilane

A variety of cyclopropenes undergo direct silylation using (trifluoromethyl)trimethylsilane in the presence of a copper-bisphosphine catalyst; under these conditions, cyclopropenes that might otherwise undergo ring-opening are silylated efficiently.     

Cyclopropenes in the 1,3-dipolar cycloaddition with carbonyl ylides: experimental and theoretical evidence for the enhancement of sigma-withdrawal in 3-substituted-cyclopropenes

The carbonyl ylide dipoles generated by the dirhodium tetra-acetate-catalyzed decomposition of diazocarbonyl precursors 1, 5, and 8 cycloadd to 3-substituted 1,2-diphenylcyclopropenes 3a-e and 3,3-disubstituted cyclopropenes 13, 14, 19, and 20 to give polycyclic compounds with 8-oxatricyclo[3.2.1.0(2,4)]octane and 9-oxatricyclo[3.3.1.0(2,4)]nonane frameworks. Generally, reactions proceed stereoselectively to give adducts of exo stereochemistry with the approach of the carbonyl ylide dipoles from the less-hindered face of cyclopropenes. The electronic properties of the substituent at the C3 position of cyclopropenes play an important role in governing the reactivity of cyclopropenes: when the C3 position is substituted by electron-acceptors such as the methoxycarbonyl or cyano groups, the yields of adducts are decreased significantly or no adducts can be detected at all. Relative reactivities of cyclopropenes were quantified by competition experiments to give the best correlation with sigmaF-Taft constants. Both measured photoelectron spectra and ground-state calculations of a series of 1,2-diphenylcyclopropenes indicate considerable lowering of cyclopropene pi-HOMO energies by substitution with an acceptor group. Such changes in electronic structures of cyclopropenes may cause the inversion of frontier molecular orbital (FMO) interactions from HOMO(cyclopropene)-LUMO(ylide) to LUMO(cyclopropene)-HOMO(ylide) type. In terms of philicity, nucleophilic properties of acceptor-substituted cyclopropenes are diminished to such an extent that these species are no longer good nucleophiles in the reaction with carbonyl ylides, and neither are they good electrophiles, being unreactive. This was shown by the B3LYP calculations of addends.     

Synthesis and application of alkenylstannanes derived from base-sensitive cyclopropenes

In the presence of stoichiometric potassium fluoride, a range of base-sensitive cyclopropenes undergo direct stannylation using (pentafluoroethyl)tributylstannane. The resulting stannylcyclopropenes serve as precursors to a variety of tetrasubstituted cyclopropenes that might otherwise be difficult to access using alternative methods.     

Catalytic enantioselective hydrostannation of cyclopropenes

The first examples of catalytic enantioselective hydrostannation of the C=C double bond of cyclopropenes has been demonstrated. This method allows for the efficient synthesis of 2,2-disubstituted cyclopropylstannanes with high degrees of diastereo- and enantioselectivity. The facial selectivity of this reaction is entirely controlled by steric factors. A variety of functional groups at C-3 of the cyclopropenes were tolerated.     

Enantioselective palladium-catalyzed carbozincation of cyclopropenes

A highly enantioselective palladium-catalyzed carbozincation of cyclopropenes has been developed. The intermediate cyclopropylzinc species, after transmetalation with copper, were trapped with various electrophiles. This one-pot procedure furnished functionalizied cyclopropenes with excellent diastereo- and enantioselectivity.     

Dianion approach to chiral cyclopropene carboxylic acids

[reaction: see text] In this Letter, we describe a general method for preparing the dianions of cyclopropene carboxylic acids, and we show that their subsequent reactions with electrophiles provide a general means for selectively introducing diverse types of functional groups. This provides a general method for the synthesis of chiral 1,2-disubstituted cyclopropenes, and opens new avenues for the enantioselective preparation of cyclopropenes.     

Synthesis of polyfunctionalized vinyl cyclopropanes via the NaI-catalyzed ring-opening cyclization of doubly activated cyclopropenes with 1,1-bis(phenylsulfonyl)ethylene

A NaI-catalyzed reaction of 3,3-bis(alkoxycarbonyl)cyclopropenes in the presence of 1,1-bis(phenylsulfonyl)ethylene providing an efficient route to a series of polyfunctionalized vinyl cyclopropanes is described. The reaction is general for a range of different 3,3-bis(alkoxycarbonyl)cyclopropenes affording the products in moderate to high yields. A plausible rationale for this transformation is discussed.     

Silver‐Catalyzed Allylation of Ketones and Intramolecular Cyclization through Carbene Intermediates from Cyclopropenes Under Ambient Conditions

Tandem C?C bond formation was achieved through silver‐catalyzed ring‐opening of cyclopropenes via carbene intermediates. The reaction of cyclopropenes in the presence of a silver catalyst gave indene derivatives under ambient conditions. In contrast, the insertion of organozinc reagents to silver carbene or allylic cation intermediates afforded allylmetal intermediates for the tandem allylation of carbonyl compounds.     

Rhodium-catalyzed hydroformylation of cyclopropenes

The first catalytic diastereo- and enantioselective hydroformylation of cyclopropenes was demonstrated. The reaction proceeds efficiently under very mild conditions and low catalyst loadings providing high yields of cyclopropylcarboxaldehydes. This novel methodology represents a convenient, atom-economic approach toward optically active cyclopropylcarboxaldehydes from readily available prochiral cyclopropenes.     

Synthesis and Reactivity Comparisons of 1‐Methyl‐3‐Substituted Cyclopropene Mini‐tags for Tetrazine Bioorthogonal Reactions

Substituted cyclopropenes have recently attracted attention as stable “mini‐tags” that are highly reactive dienophiles with the bioorthogonal tetrazine functional group. Despite this interest, the synthesis of stable cyclopropenes is not trivial and their reactivity patterns are poorly understood. Here, the synthesis and comparison of the reactivity of a series of 1‐methyl‐3‐substituted cyclopropenes with different functional handles is described. The rates at which the various substituted cyclopropenes undergo Diels–Alder cycloadditions with 1,2,4,5‐tetrazines were measured. Depending on the substituents, the rates of cycloadditions vary by over two orders of magnitude. The substituents also have a dramatic effect on aqueous stability. An outcome of these studies is the discovery of a novel 3‐amidomethyl substituted methylcyclopropene tag that reacts twice as fast as the fastest previously disclosed 1‐methyl‐3‐substituted cyclopropene while retaining excellent aqueous stability. Furthermore, this new cyclopropene is better suited for bioconjugation applications and this is demonstrated through using DNA templated tetrazine ligations. The effect of tetrazine structure on cyclopropene reaction rate was also studied. Surprisingly, 3‐amidomethyl substituted methylcyclopropene reacts faster than trans‐cyclooctenol with a sterically hindered and extremely stable tert‐butyl substituted tetrazine. Density functional theory calculations and the distortion/interaction analysis of activation energies provide insights into the origins of these reactivity differences and a guide to the development of future tetrazine coupling partners. The newly disclosed cyclopropenes have kinetic and stability advantages compared to previously reported dienophiles and will be highly useful for applications in organic synthesis, bioorthogonal reactions, and materials science.     

Rh2(S-PTAD)4-catalyzed asymmetric cyclopropenation of aryl alkynes

Rh₂(S-PTAD)₄ is an effective catalyst for the asymmetric cyclopropenation of aryl alkynes using a siloxyvinyldiazoacetate as the carbenoid precursor. Upon deprotection of the silyl protecting group, highly enantioenriched cyclopropenes bearing geminal acceptor groups can be accessed. These cyclopropenes undergo regioselective rhodium(II)-catalyzed ring expansion to furans.     

Main fragmentation routes of functionally substituted cyclopropenes under electron impact

The behaviour of substituted cyclopropenes under electron impact is to a large extent determined by the presence of the unsaturated three-membered ring which is capable of efficient delocalization of the positive charge. The loss of one of the substituents at the C(3) position of the small ring is characteristic for the fragmentation of cyclopropenes; the loss of the substituent which is less electron donating occurs preferentially. The presence of substituents with heteroatoms on the three-membered ring may lead to changes in the fragmentation scheme characteristic for the specific set of substituents.     

Co-complexes derived from alkene insertion to alkyne-dicobaltpentacarbonyl complexes: insight into the regioselectivity of pauson-khand reactions of cyclopropenes

Described are the X-ray crystallographic and spectral properties of Co-complexes that were isolated from two Pauson-Khand reactions of chiral cyclopropenes. These are the first examples of isolated Co-complexes derived from the putative alkene-insertion intermediates of Pauson-Khand reactions. The binuclear Co-complexes are coordinated to mu-bonded, five-carbon "flyover" carbene ligands. It is proposed that the complexes result from cyclopropane fragmentation subsequent to alkene insertion. The observation of these metal complexes provides a rationale for the origin of regioselectivity in Pauson-Khand reactions of cyclopropenes.     

Lipidated cyclopropenes via a stable 3-N spirocyclopropene scaffold

Lipidated cyclopropenes serve as useful bioorthogonal reagents for imaging cell membranes due to the cyclopropene’s small size and ability to ligate with pro-fluorescent tetrazines. Previously, the lipidation of cyclopropenes required modification at the C3 position because methods to append lipids at C1/C2 were not available. Herein, we describe C1/C2 lipidation with the biologically active lipid ceramide and a common phospholipid using a cyclopropene scaffold whose reactivity with 1,2,4,5-tetrazines has been caged.     

Zinc‐Catalyzed Synthesis of Allylsilanes by Si−H Bond Insertion of Vinyl Carbenoids Generated from Cyclopropenes

Allylsilanes have long been recognized as valuable building blocks for organic synthesis. A zinc‐catalyzed reaction of cyclopropenes and hydrosilanes provides a convenient route to these versatile unsaturated organosilanes. In this transformation, ZnBr₂ serves as an efficient catalyst, allowing the generation of a zinc vinyl carbenoid intermediate, which is subsequently involved in a Si−H bond insertion. The process shows broad scope, and is amenable to substituted and functionalized cyclopropenes or the functionalization of polysiloxanes. Moreover, zinc‐catalyzed carbene insertion into a Ge−H bond is reported for the first time.     

Silver-catalyzed ring-opening of cyclopropenes: preparation of tertiary α-branched allylic amines

Herein we report a silver-catalyzed ring-opening of cyclopropenes by addition of amines. This transformation is thought to occur via an argentocarbenium intermediate and affords tertiary α-branched allylic amines in good yields and high regioselectivity. The protocol applies to various primary and secondary amines, as well as sterically hindered cyclopropenes. Friedel–Crafts cyclization of the cationic intermediate occurs as a competitive pathway to form methyl-indene.     

Catalytic Synthesis of Trifluoromethyl Cyclopropenes and Oligo-Cyclopropenes

The synthesis of trifluoromethylated cyclopropenes is often associated with important applications in drug discovery and functional materials. In this report, we describe the use of readily available chiral rhodium(II) catalysts for a highly efficient asymmetric cyclopropenation reaction of fluorinated donor–acceptor diazoalkanes with a broad variety of aliphatic and aromatic alkynes. Further studies highlight the unique reactivity of fluorinated donor–acceptor diazoalkanes in the synthesis of oligo-cyclopropenes. Subsequent C−H functionalization of trifluoromethyl cyclopropenes furnishes densely substituted cyclopropene frameworks and also allows the alternative synthesis of bis-cyclopropenes.     

Zinc-Catalyzed Synthesis of Allylsilanes by Si−H Bond Insertion of Vinyl Carbenoids Generated from Cyclopropenes

Allylsilanes have long been recognized as valuable building blocks for organic synthesis. A zinc-catalyzed reaction of cyclopropenes and hydrosilanes provides a convenient route to these versatile unsaturated organosilanes. In this transformation, ZnBr₂ serves as an efficient catalyst, allowing the generation of a zinc vinyl carbenoid intermediate, which is subsequently involved in a Si−H bond insertion. The process shows broad scope, and is amenable to substituted and functionalized cyclopropenes or the functionalization of polysiloxanes. Moreover, zinc-catalyzed carbene insertion into a Ge−H bond is reported for the first time.     

Recent developments of cyclopropene chemistry

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).     

Rhodium(III)‐Catalyzed Transannulation of Cyclopropenes with N‐Phenoxyacetamides through C?H Activation

An efficient rhodium(III)‐catalyzed synthesis of 2H‐chromene from N‐phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three‐carbon unit in rhodium(III)‐catalyzed C(sp²) H activations.