Methylenecyclopentanes => allylic

Chemoselectivity in the cycloaddition of 2-methylenecycloheptenone (174) changes on addition of In(acac)3. The allylic carbonate 175 reacts with the ketone 174 in the presence of In(acac)3 to give the methylenetetrahydrofuran 176, and the methylenecyclopentane 177 is obtained in its absence[l 13], The cycloaddition of ynones to produce the methylenetetrahydrofuran proceeds smoothly only in the presence of In(acac)3 (10 mol%)[114]. 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

Trimethylsilyl)methylenecyclopropane (36 equation 15) is usable instead of methylenecyclopro-pane in reactions with electron deficient alkenes involving [PdCp(T) -allyl)]/PPr 3, giving silylated methylenecyclopentanes (37) and (38) in good yields and with better selectivities than those obtained from unsubstituted methylenecyclopropane (26). The trimethylsilyl group can be easily removed by protonolysis with trifiuoroacetic acid. ... 

Another interesting point is the regioselectivity of these [3+2]-cyeloadditions. Whenever a 2-substituted methylenecyclopentane is detected in a codimerization, catalyzed by a Pd(0) compound, the substitution pattern is the same as found in [3 -f 2]-cycloadditions starting with 2-[(trimethylsilyl)methyl]allyl acetates 183) (Eq. 85). 

The two Pd(0) or Ni(0) catalyzed [3+2]-cycloadditions starting with the readily accessible trimethylenemethane -precursors [2-(acetoxymethyl)-3-allyl]trimethyl-silan, methylenecyclopropane, and their substituted derivatives are important new methods for the synthesis of methylenecyclopentanes. Because of the simplicity with which many problems of cyclopentane-syntheses can be solved in a convenient one pot reaction this new methodology may be compared with the synthesis of six-membered rings by the powerful 4+2]-cycloaddition of the Diels-Alder reaction. 

With Ni(0) catalysts they can react by two different reaction mechanism which give the possibility of synthesizing methylene-cyclopentanes with different substituent patterns (see Eqs. 81, 86 and 87). In Table 11 some of the most interesting results obtained in the preparation of methylenecyclopentanes from [(2-acetoxymethyl)-3-allyl]trimethylsilan or methylenecyclopropanes and electron deficient olefins by this new [3+2]-cycloaddition methodology are summarized. 

Acetoxymethyl-3-allyltrimethylsilane is a bifunctional or conjunctive reagent that provides an efficient and versatile means of synthesizing methylenecyclopentanes via [3 + 2] cy-cloaddition18 In the presence of catalytic amounts of an appropriate palladium(O) complex, the combination of the allyl acetate and allylsilane functionalities results in the formation of a metal-stabilized trimethylenemethane unit (TMM-Pd). This is able to undergo Smooth [3 + 2] cyeloaddition reactions with electron-deficient olefins. 

The Heck reaction of oximes derived from allyl ketones is followed by cyclization to give isoxazolines. An intramolecular Heck reaction of substituted 6-chloro-l-hexenes readily affords the methylenecyclopentanes ... 

Cycloadditions. Methylenec alkenes photochemically and in the pre leads to methylenecyclopentane product tituent is at an allylic position. 

Cycloadditions. Methylenecyclopropane reacts with electron-deficient alkenes photochemically and in the presence of BU2S2. This free radical reaction leads to methylenecyclopentane products, in which the electron-withdrawing substituent is at an allylic position. 

Using the catalyst system based on [Ni(allyl)(cod)l [BARF] and Wilke s aza-phospholene ligand, several 1,6-dienes including diene 48 were converted to exo-methylenecyclopentanes 49 through the asymmetric cycloisomerization with enantiomeric excess of up to 91% (Scheme 28) (66). 

Other resnlts obtained by Tsnji s group up to 1987 using allyl carbonates are carbony-lations to afford /3,y-nnsatnrated esters " (Scheme 3) (see Sect. VI.3), cycloadditions of trimethylenemethane palladium complex to afford methylenecyclopentanes (Scheme 3), and cycloadditions of zwitterions to afford substituted vinylcyclopentanes (Scheme 4) (see Sect. V.2.5.2). 2-Butene-1,4-diol dicarbonates afford a variety of cyclic strnctnres by reaction with dinncleophiles nnder Pd(0) catalysis (see Sect. I). The first case reported seems to be the formation of the vinylcyclopropane of Scheme 44" ... 

The transfer of the TMM fragment from the TMM-Pd to an olefin leads to the formation of a methylenecyclopentane. Thus, generation of the OTMM-Pd complex followed by the transfer of the OTMM moiety to an olefin would be expected to give a cyclopen-tanone (Scheme 27). However, the 2-(trimethylsiloxy)allyl methyl carbonate, an OTMM... 

Total syntheses of diterpenoid hydrokempenones have been accomplished by Paquette et al.,f using the Pd-catalyzed [3 + 2] cycloaddition methodology. One example is outlined on Scheme 43 and describes the synthesis of an isomeric compound 208 of 3/3-hydroxy-7/3-kemp-8(9)-en-6-one, a defense secretion agent of the neotropical species Nasutitermes octopilis. 3-AUcoxy-2-cyclohexenone 204 was efficiently functionalized and transformed to bicylic adduct 205 via a Robinson annulation reaction. Reduction of the double bond followed by condensation of dimethyl carbonate and oxidation gave the keto ester 206, which was treated with [2-(acetoxymethyl)-3-allyl]trimethylsilane, palladium acetate, and triisopropyl phosphite in refluxing tetrahydrofuran to afford a 98% yield of 207. Substituted methylenecyclopentane 207 was then functionalized by stereoselective reduction and protections, and final closure was done under basic conditions after an ozonolysis step. A modified Barton-McCombie reaction produced the desired tetracyclic adduct 208. 

Annulations. The primary allylic halide 2-chloromethyl-3-trimethylsilyl-l-propene or the mesylate derived from the corresponding alcohol behaves as a hifunctional reagent possessing both nucleophilic and electrophilic reaction centers. For example, they have been shown to participate in [3 + 2] carbon annulations for the constmction of methylenecyclopentanes. The reaction proceeds through a Lewis acid-promoted conjugate addition (Sakurai reaction) followed by an internal alkylation of the derived ketone enolate (eq 3). 

Trimethylsilylmethyl)allyl aeetate (80), whieh has a silyl group in the allylic position undergoes a formal [3 + 2] eyeloaddition reaction with electron deficient alkenes to give methylenecyclopentane derivatives 84. Following oxidative addition, elimination of the TMS group, faeilitated by... 

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