A new approach to helical primary structures of four-membered rings: (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane

A new approach to helical primary structures of four-membered rings uses a cycloaddition of a trimethylenketeniminium salt to suitable tailored methylenecyclobutanes to assemble the desired carbon framework. The results are short and effective syntheses of (M)-trispiro[3.0.0.3.2.2]tridecane [(M)-5], and (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane [(P)- and (M)-24]. Unlike helices of three-membered rings, the specific rotation decreases, as the length of the helix increases.     

A Convergent Strategy for the Asymmetric Synthesis of Enantiomerically Pure Bicyclic Compounds by Using a Silicon-Directed Cycloaddition Reaction: The Synthesis of Enantiomerically Pure Bicyclo[3.2.0]hept-2-en-6-one

An asymmetric allylmetalation followed by a silicon-stereodirected cycloaddition gives enantiomerically pure bicyclic compounds. The synthesis of enantiopure 1 (see scheme) in a yield of 65–74 %, 93 % ee, and >98 % de provides an illustration of the efficacy of the method. The preferential formation of 1 rather than its diastereoisomer (32:1), during the cycloaddition step, matches the result predicted by RHF and density functional theory studies.     

Formation of 3,4-dimethyl-2-pyrones from allene carboxylates and 2-silyloxydienes via 3-carboethoxyethylidene cyclobutanols

The 3-carboethoxyethylidene cyclobutanols 4 are prepared in two steps via [2+2] cycloaddition of the 2-silyloxydienes 1 and the allene carboxylate 2 followed by acidic hydrolysis. Treatment of these cyclobutanols 4 with various bases affords good yields of the substituted 3,4-dimethyl-2-pyrones 6. The proposed mechanism involves ring opening of the metal alkoxide 7 to give the carbanion 8, which undergoes proton transfer to give the more stable carbanion 9 and double bond isomerization to give the enolate 10, which then forms the pyrone ring 6 via attack on the ester via 11.     

Cycloaddition of keteniminium with terminal alkynes toward cyclobuteniminium and their use in Diels–Alder reactions

An efficient access to cyclobutanone derivatives has been developed via a ‘one-pot’ [2+2]/[4+2] sequence involving keteniminium and cyclobuteniminium salts as key intermediates. A broad range of novel cyclobuteniminium salts have been prepared via [2+2] cycloaddition of keteniminium salts and alkynes. The resulting [2+2] adducts were then further transformed by Diels–Alder reaction with various dienes to afford cyclobutanone derivatives in good yields. A density functional theory (DFT) based computational study has been performed to obtain insight into the nature of the cycloaddition reactions and to investigate the difference in reactivity of cyclobuteniminium salts. Finally, the usefulness of cyclobutanone derivatives has been demonstrated by ring expansion reactions affording lactone, lactame, and cyclopentanone derivatives.     

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.     

Carbon‐13 Nuclear Magnetic Resonance Spectroscopic Analyses of 3‐Aryl‐3‐hydroxyl‐2,2,4,4‐tetramethylcyclobutanones and Related Compounds

A series of 2‐aryl‐2‐hydroxy‐1,1,3,3‐tetramethyl‐5,8‐dioxaspiro[3.4]octanes ( 1 ), 3‐aryl‐3‐hydyoxyl‐2,2,4,4‐tetyramethylcyclobutanones ( 2 ), and l‐aryl‐2,2,4‐trimethyl‐1,3‐pentadiones ( 3 ) were studied using ¹³C NMR analyses. The chemical shifts of C‐c are dependent on the substituent groups on the phenyl ring for compounds 1 (ρ =‐0.966, R² = 0.987) and 2 (ρ = ?1.378, R² = 0.998). The chemical shifts of C‐a follow a similar trend (ρ =?0.926, R² = 0.989). In the case of compounds 3 , C‐c yielded the opposite trend with very poor correlation coefficiency (ρ = 1.22, R² = 0.179). This result reveals the field effect of a polar bond and resonance‐induced changes in pi electron‐density at C‐1 on the cyclobutanering series.     

A Simple Multistep Conversion of 1,2‐Dihydro‐1,1‐dimethoxynaphthalen‐2‐ones to (3,4‐Dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates

On irradiation (λ=350 nm) in the presence of 1,1‐dimethoxyethene, naphthalene‐1,2‐dionemonoacetals 1 regioselectively afford 1,1,4,4‐tetramethoxycyclobuta[a]naphthalen‐3‐ones 3 . Sequential deprotection of these bis‐acetals first lead to 1,1‐dimethoxycyclobuta[a]naphthalene‐3,4‐diones 4 and then to cyclobuta[a]naphthalene‐1,3,4‐triones 6 , which, in turn, are converted into (3,4‐dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates 7 by treatment with SiO₂/MeOH/air.     

Use of cyclobutyl derivatives as intermediates in the synthesis of 1,2a,3,8b-tetrahydro-2H-cyclobuta[c]chromenes

Starting from cyclobutanones and tertiary cyclobutanols several new chromenes containing a cyclobutane ring have been prepared by acid catalyzed intramolecular alkylation of an oxygen-carrying aromatic ring. Interestingly one of the cyclobutanols leads to 3-[(4-methoxyphenoxy)methyl]-2,2,3-trimethylcyclopentanone that is a precursor in the synthesis of the carotenoid pigment capsorubin.     

Abnormal Beckmann rearrangement of steroidal α-chlorocyclobutanone oximes: the fragmentation-substitution reaction

α,α-Dichlorocyclobutanones of various substitution patterns, readily available by the thermal cycloaddition of dichloroketene to steroid olefins, were selectively dehalogenated and further transformed to α-chlorocyclobutanone oximes. In contrast to the Beckmann rearrangement of the α-unsubstituted oximes, α-chlorocyclobutanone oximes, on treatment with thionyl chloride in benzene, gave normal and abnormal reaction products. In all reactions studied, the Beckmann fragmentation-substitution was the major process. The rearrangement of α-chlorocyclobutanone oximes is the key step of the novel method for geminal functionalization of carbonyl carbon atom in ketones and regioselective vicinal functionalization of unsymmetrical olefins. The regiochemistry observed in the rearrangements is supported by semiempirical calculations (AM1).     

Stereoselective reduction of N-(3-arylcyclobutylidene)amines

N-Alkylimines derived from cyclobutanones have not been evaluated in depth as building blocks for organic synthesis, although these compounds are, among others, good precursors for interesting 3-arylcyclobutylamines. The reduction of various N-alkyl-N-(3-arylcyclobutylidene)amines with LiAlH₄ yielded cis-substituted cyclobutylamines as the only stereoisomers. When borane was used as a reducing agent, an intermediate imine-borane complex could be isolated as a stable compound.