Photocycloaddition of Six‐Membered Cyclic Enones to Propen‐2‐yl Isocyanate

On irradiation in the presence of propen‐2‐yl isocyanate ( 4 ), six‐membered cyclic enones 3 are converted into regio‐ and stereoisomeric mixtures of [2+2] cycloadducts 5 – 10 ; the preferentially formed HT products, 5 – 8 , can be converted into the corresponding bicyclic amines by acid hydrolysis, whereas, under these conditions, the regioisomeric HH‐isocyanato derivatives undergo a retro‐Mannich reaction.     

Formal γ−C−H Functionalization of Cyclobutyl Ketones: Synthesis of cis-1,3-Difunctionalized Cyclobutanes

1,3-Difunctionalized cyclobutanes are an emerging scaffold in medicinal chemistry that can confer beneficial pharmacological properties to small-molecule drug candidates. However, the diastereocontrolled synthesis of these compounds typically requires complicated synthetic routes, indicating a need for novel methods. Here, we report a sequential C−H/C−C functionalization strategy for the stereospecific synthesis of cis-γ-functionalized cyclobutyl ketones from readily available cyclobutyl aryl ketones. Specifically, a bicyclo[1.1.1]pentan-2-ol intermediate is generated from the parent cyclobutyl ketone via an optimized Norrish-Yang procedure. This intermediate then undergoes a ligand-enabled, palladium-catalyzed C−C cleavage/functionalization to produce valuable cis-γ-(hetero)arylated, alkenylated, and alkynylated cyclobutyl aryl ketones, the benzoyl moiety of which can subsequently be converted to a wide range of functional groups including amides and esters.     

Synthesis of heterospiranes by cyclization of dinucleophiles with 1,1-bis(tosyloxymethyl)cyclopropane and -cyclobutane

A variety of heterocyclic spiranes were prepared by cyclization of dinucleophiles with 1,1-bis(tosyloxymethyl)cyclopropane and -cyclobutane.     

Stereoselective Synthesis of [3.3.0]‐Fused γ‐Butyrolactones of Carbohydrates

A facile and stereoselective method is described for the preparation of fused 2,3‐γ‐butyrolactones of lyxofuranose from the unexpected rearrangement in basic media of the photocycloadduct between homochiral 2(5H)‐furanones and vinylene carbonate.     

Visible‐Light‐Driven Strain‐Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

There are a limited number of ring‐contraction methodologies which convert readily available five‐membered rings into strained four‐membered rings. Here we report a photo‐induced radical‐mediated ring contraction of five‐membered‐ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron‐rich alkenyl boronate complex, leading to an α‐boryl radical. Upon one‐electron oxidation, ring‐contractive 1,2‐metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups.     

Synthesis of multi-substituted cyclobutenes: Cyclic strategy for [2 + 2] cycloaddition of ketene silyl acetals with propiolates

Cyclic ketene silyl acetals were utilized for [2 + 2] cycloaddition with propiolates to prevent an undesired electrocyclic ring opening reaction. Trimethylaluminum catalyzed this cycloaddition to afford the cyclobutene derivatives in high yields. The advantage of this reaction was highlighted by the successful application of β-substituted propiolates to afford the multi-substituted cyclobutenes. Furthermore, we applied this methodology to the late stage functionalization of natural product artemisinin.     

Rapid access to cis-cyclobutane γ-amino acids in enantiomerically pure form

The (+)-(1R,2S) and (−)-(1S,2R) stereoisomers of 2-(aminomethyl)cyclobutane-1-carboxylic acid have been prepared using a short and efficient strategy, which employs the photochemical [2+2] cycloaddition reaction between ethylene and an unsaturated γ-lactam as the key step.     

Unusual ring-chain tautomerism in bicyclo[4.2.0]octane derivatives

A new type of ring-chain tautomerism, which consists of the reversible conversion of bicyclo[4.2.0]octane derivatives into trisubstituted enamines was found and studied by ¹H NMR spectroscopy. The starting materials were prepared by the stereoselective reaction of (E)-3,3,3-trichloro-1-nitropropene with cyclohexanone enamines.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: (2+2) Cycloadditions with Vinyl Ethers

The title compound (short version: BTE) occurs in (E)‐ and (Z)‐isomers (both with b.p. of ca. 100°) which equilibrate with nucleophilic catalysts. Both undergo (2+2) cycloadditions with methyl vinyl ether at 25°. Three stereogenic centers in the cyclobutanes led to four rac‐diastereoisomers, which were obtained in pure and crystalline state. The structures were elucidated by ¹⁹F‐NMR spectroscopy and confirmed by two X‐ray analyses. The cycloadditions were not stereospecific: e.g., (E)‐BTE furnished 73% trans‐adducts (with respect to the CF₃ groups) and 27% cis‐adducts. The loss of stereochemical integrity occurs in the intermediate gauche‐zwitterions which can cyclize or rotate, but not dissociate. Under extreme conditions (2M LiClO₄ in Et₂O, 70°, 3 months), the thermodynamic equilibrium of the four cyclobutanes was achieved. Considerations of Coulombic attraction and conformational strain in the zwitterionic intermediates allow us to rationalize the observed proportions of diastereoisomeric cyclobutanes. Ethyl vinyl ether and butyl vinyl ether furnished cyclobutanes in similar diastereoisomer ratios.