Cycloaddition precursor cyclopentane

Dauben s group utilized the same retrosynthetic disconnections, but chose to add more functionality to the cycloaddition precursor. From a simple frawi-disubstituted cyclopentane, Dauben used an aldol reaction of a cyclopropylvinyl aldehyde to prepare the cycloaddition precursor. The diazo-substituted (3-ketoester was completed using a Roskamp-Padwa coupling followed by diazo-transfer. Addition of rhodium acetate to the diazo substituted p-ketoester 179 led to an excellent 86% yield of the correct diastereomer (Scheme 4.42). 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

The synthesis of new 11-deoxyprostaglandin analogs with a cyclopentane fragment in the oo-chain, prostanoid 418, has been accomplished by a reaction sequence involving nitrile oxide generation from the nitromethyl derivative of 2-(oo-carbomethoxyhexyl)-2-cyclopenten-l-one, its 1,3-cycloaddition to cyclopenten-l-one and reductive transformations of these cycloadducts (459). Diastereoisomers of a new prostanoid precursor 419 with a 4,5,6,6a-tetrahydro-3aH-cyclopent[d isoxazole fragment in the oo-chain have been synthesized. Reduction of 419 gives novel 11-deoxyprostanoids with modified a- and oo-chains (460). 

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. 

In nickel-catalyzed reactions, the cyclopentane with the electron-withdrawing group in the 3-position (relative to the exo-methylene group) is formed almost exclusively. This is in contrast to the palladium-catalyzed, formal [3-1-2] cycloaddition employing 2-(trimethylsilylme-thyl)prop-3-enyl acetate as precursor, which presumably follows a mechanistically different, ionic pathway. In palladium-catalyzed MCP reactions of that type, the observed selectivity is markedly dependent on the specific reactants. 

DicWoroketene is particularly reactive, and reductive dechlorination of the product with zinc and acetic acid allows access to the cyclobutanone from formal addition of ketene itself. Thus, cycloaddition of dichloroketene with cyclopentadiene, followed by dechlorination and Baeyer-Villiger oxidation gave the lactone 173, a usehil precursor to various oxygenated cyclopentane products (3.117). Intramolecular cycloaddition reactions of ketenes can allow the formation of bicyclic and polycyclic products using otherwise unstable ketene intermediates. ... 

Diastereomers of 13 were separated before the cycloaddition reaction since only one isomer was expected to adopt the sterically less demanding conformation in the transition state while the other diastereomer would suffer from severe steric congestion. Both diastereomers of precursor 13 were treated with KHMDS and the propynyliodonium salt, 12. The tandem cycloaddition reaction of the substrate 13a, to our pleasant surprise, gave tetraquinane product 11 in 50% yield, while 13b did not yield any cycloaddition product. These results allowed us to determine the relative stereochemistry of 13a and 13b as depicted. The sequential formation of alkylidene carbene and the TMM diradical intermediates transformed the cyclopentane substrate with a linear chain into the tetracyclic compound (Scheme 4). The core stmcture... 

There have been reports of a number of reactions of CPNA 73 that result in cleavage of the strained C—C o-bond under thermal conditions. The formed reactive intermediate 74 undergoes insertion and cheletropic [1+2]-, [3+2]-, and [3-1-4] cycloaddition reactions under thermal conditions (Scheme 6.13a). The reactivity profiles reported to date are consistent with such a a-delocalized singlet species 74 that can react either as a 1,1- or as a 1,3-dipole. Moreover, the 2-alkylidenecyclopropanone acetal 75 derived from a CPNA 76 is a useful precursor of dialkoxy trimethylenemethane (TMM) 77. MUd thermolysis of 75 in the presence of an electrophile generates 77, which undergoes a [3+2] cycloaddition to form cyclopentane derivative 78 (Scheme 6.13b). These results were reviewed by Nakamura and coworkers [32]. 

Finally, both Oppolzer and Kametani and their respective collaborators have adapted their steroidal syntheses based upon intramolecular o -quinodimethane cycloaddition to achieve asymmetric induction by incorporation of an optically active cyclopentane moiety in the cyclization precursor. 

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