Cycloheptene synthesis

Kiyama, R., Honma, T., Hayashi, K., Ogawa, M., Hara, M., Fujimoto, M., and Fujishita, T. Angiotensin II receptor antagonists. Design, synthesis, and in vitro evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f oxepin derivatives. 

Two suggested methods of nortriptyline synthesis are based on the N-demethylation of amitriptyline. The third way utilizes the reaction of methylamine with 5-(3-bromopropyli-den)-10,11 -dihydro-57f-dibenz [a,d]cycloheptene (7.1.18). 

W. Pitsch, A. Russel, M. Zabel, and B. Konig, Synthesis of a functionalized cyclohepten-one from erythronic acid-4-lactone, Tetrahedron, 57 (2001) 2345-2347. 

Few examples of total syntheses have been reported that involve an intramolecular nitrile oxide cycloaddition and ensuing reduction to an aminoalcohol. The very first example was reported by Confalone et al. (334) and involved a synthesis of the naturally occurring vitamin biotin (287). The nitro precursor 284 was easily prepared from cycloheptene. When treated with phenyl isocyanate-triethylamine, cycloaddition led to the all-cis-fused tricyclic isoxazoline 285 with high stereoselectivity (Scheme 6.102). Reduction with LiAlFLj afforded aminoalcohol 286 as a... 

Eberbach and coworkers have made an extensive study of the thermal chemistry and photochemistry of ethenyloxiranes (81CB1027 and refs, therein). Thermal isomerization can involve mainly either C—O (Scheme 8) or C—C (Scheme 9) cleavage. The reluctance of (11) to generate an ylide may be due to the fact that allowed, conrotatory opening would give a strained species (12) (cf. OEO-cycloheptene). The photoisomerization of ethenyloxiranes can involve either C—O (Scheme 10) or C—C (Scheme 11) cleavage. Photolysis of (13) led to the synthesis of the ketone tautomer (14) of a phenol (Scheme 12) (80TL463). 

Nitrile oxide J -I- 2 cycloaddition.1 A key step in a recent stereospecific synthesis of biotin (6) from cycloheptene (1) is an intramolecular [3 + 2]cyclo-addition of a nitrile oxide (a), obtained by dehydration of a primary nitro compound (3), preferably with phenyl isocyanate. This cycloaddilion is more efficient than the well-known olefinic nitrone cycloaddition. The carbon atoms in 6 derived from cycloheptene are marked with asterisks. 

Since reactivity of alkenes increases with increasing alkyl substitution, hydration is best applied in the synthesis of tertiary alcohols. Of the isomeric alkenes, cis compounds are usually more reactive than the corresponding trans isomers, but strained cyclic isomeric olefins may exhibit opposite behavior. Thus, for example, frans-cyclooctene is hydrated 2500 times faster than cw-cyclooctene.6 Similar large reactivity differences were observed in the addition of alcohols to strained trans cycloalkenes compared with the cis isomers. frans-Cycloheptene, an extremely unstable compound, for instance, reacts with methanol 109 faster at —78°C than does the cis compound.7... 

Iron carbonyls also mediate the cycloaddition reaction of allyl equivalents and dienes. In the presence of nonacarbonyldiiron a,a -dihaloketones and 1,3-dienes provide cycloheptenes (Scheme 1.5) [14,15]. Two initial dehalogenation steps afford a reactive oxoallyliron complex which undergoes a thermally allowed concerted [4 + 31-cycloaddition with 1,3-dienes. The 1,3-diene system can be incorporated in cyclic or heterocyclic systems (furans, cyclopentadienes and, less frequently, pyrroles). Noyori and coworkers applied this strategy to natural product synthesis, e.g. a-thujaplicin and P-thujaplicin [14, 16]. 

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