1.3- Dipolar cycloaddition cyclopentane

Tam and coworkers [311] developed a method for the synthesis of 1,3-disubsti-tuted cyclopentanes 6/4-124 and cyclopentenes. Thus, reaction of the condensed isoxazolines 6/4-123, easily obtainable by a 1,3-dipolar cycloaddition, gave 6/4-124 in good yields using Mo(CO)6 (Scheme 6/4.30). 

Dipolar addition is closely related to the Diels-Alder reaction, but allows the formation of five-membered adducts, including cyclopentane derivatives. Like Diels-Alder reactions, 1,3-dipolar cycloaddition involves [4+2] concerted reaction of a 1,3-dipolar species (the An component and a dipolar In component). Very often, condensation of chiral acrylates with nitrile oxides or nitrones gives only modest diastereoselectivity.82 1,3-Dipolar cycloaddition between nitrones and alkenes is most useful and convenient for the preparation of iso-xazolidine derivatives, which can then be readily converted to 1,3-amino alcohol equivalents under mild conditions.83 The low selectivity of the 1,3-dipolar reaction can be overcome to some extent by introducing a chiral auxiliary to the substrate. As shown in Scheme 5-51, the reaction of 169 with acryloyl chloride connects the chiral sultam to the acrylic acid substrate, and subsequent cycloaddition yields product 170 with a diastereoselectivity of 90 10.84... 

Muthusamy et al. (82) prepared a number of oxacyclic ether compounds from the tandem ylide formation-dipolar cycloaddition methodology. Their approach provides a synthetic tactic to compounds such as ambrosic acid, smitopsin, and linearol. Starting with either cyclopentane or cyclohexane templates, they prepared ylide sizes of five or six, which are trapped in an intermolecular cycloaddition reaction by the addition of DMAD. The products are isolated in good overall yield. In a second system, 2,5-disubstituted cyclohexenyl derivatives are utilized to generate the pendent ylide, then, A-phenylmaleimide is added in an intermolecular reaction, accessing highly substituted oxatricyclic derivatives such as 182 (Scheme 4.43). 

Of the several types of enals derivable from aldoses (see 80 and 81), the 5,6-dideoxy-hex-5-enoses are of particular significance because of the efficient cyclization to give cyclopentane derivatives that they undergo on treatment with A-alkylhydroxylamines. The reactions are spontaneous and involve intramolecular 1,3-dipolar cycloadditions undergone by intermediate nitrones. For example, compound 272, made by treatment of 6-bromo compound 271 with zinc in moist alcohol, on reaction with A-methylhydroxylamine gives the bicyclic product 273 in 80% yield (Scheme 28).256 This process gives simple access to many functionalized cyclopentanes. 

Dipolar cycloadditions, closely related to the Diels-Alder reaction,1,2 result in the synthesis of a five-membered adduct including cyclopentane derivatives.417"426... 

Chiral Cyclopentane Synthesis From Sugars Transformation of monosaccharides into enantiomerically pure penta- substituted cyclopentanes via fragmentation and nitrone-olefin dipolar cycloaddition. 

Residual Ru species do not interfere with some subsequent transformations. Rodrigo B. Andrade of Temple University has demonstrated (Tetrahedron Lett. 2007, 48, 5367) that metathesis with an a, 3-unsaturated aldehyde such as 11 can be followed directly by phospho-nate condensation to give the doubly-homologated product 12. Philip 1. Parsons of the University of Sussex has found (Organic Lett. 2007, 9, 2613) that the nitro functional group is compatible with the Ru catalyst. The product nitro alkene 15 could be cychzed (intramolecular Michael addition) to the cyclopentane 16, or (intramolecular dipolar cycloaddition) to the cyclopentane 17. 

Damien Bonne and Jean Rodriguez of Aix-Marseille Universite employed (Organic Lett. 2008, 10, 5409) intramolecular dipolar cycloaddition to convert the initial adduct between 22 and 23 to the cyclopentane 24. They also prepared cyclohexane derivatives using this approach. 

Cycloaddition. Reaction of the 1,3-dipolar species derived from methyl 2-phenylthiocyclopropyl ketone with silyl vinyl ethers furnishes functionalized cyclopentanes. A related reaction is the trapping of a fragmented cyclobutane. ... 

The use of diphenylmethylenecyclopropanes, as opposed to methylenecyclo-propanes, greatly enhances the Pd°-induced [3 + 2] cycloaddition with alkenes to produce five-membered rings. A one-carbon ring-contraction route to cyclopentanes involves a high-pressure version of the known 1,3-dipolar addition of azides to O-silylated enolates, which removes some of the previously observed steric limitations of the reaction, so that the adduct (47) fragments, as shown, to produce the ring-contracted product (48). The intramolecular nitrile oxide... 

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