Palladium-catalyzed sequential carbon-carbon bond cleavage/formation producing arylated benzolactones

3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at the 2-position.     

Palladium-catalyzed, asymmetric Baeyer-Villiger oxidation of prochiral cyclobutanones with PHOX ligands

Described in this report is a general method for the conversion of prochiral 3-substituted cyclobutanones to enantioenriched γ-lactones through a palladium-catalyzed Baeyer-Villiger oxidation using phosphinooxazoline ligands in up to 99% yield and 81% ee. Lactones of enantiopurity ≥93% could be obtained through a single recrystallization step. Importantly, 3,3-disubtituted cyclobutanones produced enantioenriched lactones containing a β-quaternary center.     

Controllable Skeleton Rearrangement of 3‐Substituted Cyclobutanones under Basic Conditions†

Divergent skeleton rearrangements of cyclobutanones under simply basic conditions have been described. The reaction pathway is controlled by the nature of Z group on 3‐substituted cyclobutanones, leading to the formation of various lactones, lactams and acids. Preliminary results on enantioselective reaction were also reported.     

Asymmetric synthesis of cyclobutanones: synthesis of cyclobut-G

A simple, efficient, and stereoselective approach has been developed for obtaining chiral cis- and trans-disubstituted cyclobutanones from readily available alkyl- and functionalized alkyl-substituted enol ethers. The usefulness of these cyclobutanones is illustrated by an enantioselective synthesis of cyclobut-G (Lobucavir).     

Acids direct 2-styrylcyclobutanone into two distinctly different reaction pathways

Two structurally distinct carbocycles were selectively obtained by the reactions of 2-(o-styryl)cyclobutanones promoted by ytterbium salts. Treatment of the cyclobutanones with YbCl(3) in 1,4-dioxane at 100 degrees C afforded 2-(2-chloroethyl)naphthalenes. On the other hand, the reaction with Yb(OTf)(3) in chlorobenzene at 130 degrees C gave 9,10-dihydrobenzocycloocten-7(8H)-ones.     

Non-Diazo C−H Insertion Approach to Cyclobutanones through Oxidative Gold Catalysis

Cyclobutanones are synthetically versatile compounds that often require extensive effort to access. Herein, we report a facile synthesis of cyclobutanones based on the C(sp³)−H insertion chemistry of oxidatively generated gold carbenes. Various cyclobutanones were obtained in synthetically useful yields from substrates with minimal structural prefunctionalization. This discovery reveals new synthetic utilities of gold-catalyzed oxidative transformations of alkynones.     

The mass spectra of substituted cyclobutanones

The low resolution mass spectra of several di-, tri-and tetra-methylated cyclobutanones were determined at high and low ionizing voltages. The spectra are discussed in terms of the competition between loss of CO or loss of a ketene from the molecular ion of the cyclobutanone. The mass spectral results are correlated with the known photochemical behavior of the cyclobutanones and possible mechanistic implications are discussed.     

Non‐Diazo C−H Insertion Approach to Cyclobutanones through Oxidative Gold Catalysis

Cyclobutanones are synthetically versatile compounds that often require extensive effort to access. Herein, we report a facile synthesis of cyclobutanones based on the C(sp³)?H insertion chemistry of oxidatively generated gold carbenes. Various cyclobutanones were obtained in synthetically useful yields from substrates with minimal structural prefunctionalization. This discovery reveals new synthetic utilities of gold‐catalyzed oxidative transformations of alkynones.     

Synthesis of Bridged Cyclopentane Derivatives by Catalytic Decarbonylative Cycloaddition of Cyclobutanones and Olefins

Herein, we report an intramolecular rhodium‐catalyzed decarbonylative coupling between cyclobutanones and alkenes that proceeds by C?C activation and provides a distinct approach to a diverse range of saturated bridged cyclopentane derivatives. In this reaction, cyclobutanones serve as cyclopropane surrogates, reacting in a formal (4+2?1) transformation. To demonstrate the efficacy of this method, it was applied in a concise synthesis of the antifungal drug Tolciclate.     

Enantioselective Desymmetrization of Cyclobutanones: A Speedway to Molecular Complexity

Cyclobutanones hold a privileged role in enantioselective desymmetrization because their inherent ring strain allows for a variety of unusual reactions to occur. Current strategies include α‐functionalization, rearrangement, and C?C bond activation to directly convert cyclobutanones into a wide range of enantiomerically enriched compounds, including many biologically significant scaffolds. This Minireview provides an overview of state‐of‐the‐art methods that generate complexity from prochiral cyclobutanones in a single operation.     

Pd‐Catalyzed Enantioselective Ring Opening/Cross‐Coupling and Cyclopropanation of Cyclobutanones

A palladium‐catalyzed enantioselective sequential ring‐opening/cross‐coupling of cyclobutanones is disclosed that provides chiral indanones bearing C3‐quaternary stereocenters. The reaction process involves palladium‐catalyzed nucleophilic addition of cyclobutanones and aryl halides, enantioselective β‐carbon elimination, and intermolecular trapping of a transient σ‐alkylpalladium complex with boronic acids. Alternatively, an intramolecular cyclopropanation is realized through C?H bond functionalization in the absence of external coupling reagents, affording chiral cyclopropane‐fused‐indanones in good yields and enantioselectivity.     

Silylated and germylated cyclopropanones

The synthesis of trimethylsilyl- and germyl-cyclopropanones, by treating diazomethane with the corresponding trimethyl ketene, and their ring expansion to cyclobutanones are described.     

Isomerisation thermique d'alkylidenecyclobutanones : Piegeage du diradical intermediaire par migration −1,5 d'hydrogene

The biradical intermediate which results from the thermal ring fission of alkylidene cyclobutanones $\text{2}$ serves as a common precursor of isomerised cyclobutanones $\text{3}$ (1,3 carbon shift), and of dienones $\text{4}$ by way of intramolecular 1,5 hydrogen shift.     

Ring cleavage and successive aldol reaction of 3-[(trialkylsilyl)methyl]cyclobutanones

3-[(Trialkylsilyl)methyl]cyclobutanones reacted with aldehydes by activation with titanium(IV) chloride to give acyclic β,γ-unsaturated β'-hydroxyketones.     

Fused‐Ring Formation by an Intramolecular “Cut‐and‐Sew” Reaction between Cyclobutanones and Alkynes

The development of a catalytic intramolecular “cut‐and‐sew” transformation between cyclobutanones and alkynes to construct cyclohexenone‐fused rings is described herein. The challenge arises from the need for selective coupling at the more sterically hindered proximal position, and can be addressed by using an electron‐rich, but less bulky, phosphine ligand. The control experiment and ¹³C‐labelling study suggest that the reaction may start with cleavage of the less hindered distal C?C bond of cyclobutanones, followed by decarbonylation and CO reinsertion to enable Rh insertion at the more hindered proximal position.     

Cyclobutanones for the stereoselective synthesis of bifunctional macrolide intermediates

Beckmann fragmentation of the oximes 5 and 6 respectively, which were derived from the cyclobutanones 3 and 4, furnished the bifunctional five carbon units 7 and 8 with ca. 98% and 91% stereoselectivity.     

Synthesis of aminocyclopentitols from chromium carbene complex derived aminocyclobutanones

Functionalized cyclopentenones were synthesized by the diazomethane ring expansion of cyclobutanones, produced by the photochemical reaction of vinyl oxazolidinones with chromium carbene complexes.     

Ir‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene β‐Lactams and Cyclobutanones

Chiral β‐lactams and cyclobutanones are present in numerous natural and pharmaceutical products. The stereoselective construction of chiral four‐membered cyclic compounds is an ongoing challenge for the chemical community. Herein, we report a highly stereocontrolled construction of four‐membered ring (mini‐sized) β‐lactams and cyclobutanones via an Ir/ In‐BiphPHOX ‐catalyzed asymmetric hydrogenation, providing the corresponding optically active four‐membered ring carbonyl products bearing an α‐chiral carbon center with excellent yields (up to 99%) and enantioselectivities (up to 98%) under mild reaction conditions (1.0—2.5 bar H₂ for 1.0—10 h). The reaction presents wide substrate scope. Diverse transformations of the catalyzed products were also conducted to show the potential utility of this protocol.     

Expedient approach to chiral cyclobutanones: asymmetric synthesis of cyclobut-G

An efficient one-pot asymmetric synthesis of cyclobutanones from chiral enol ethers is described. The approach is illustrated with alkyl- and functionalized alkyl-substituted enol ethers (nine examples). A new enantioselective synthesis of cyclobut-G (Lobucavir) could thus be achieved.     

1-bromo-1-ethoxycyclopropane: a new reagent for cyclobutanone synthesis

A variety of of cyclobutanones have been prepared in high yield from 1-bromo-1-ethoxycyclopropane via lithiation, addition to aldehydes or ketones, and mild acid-catalyzed rearrangement of the adducts.