Cyclohexane derivatives 1,3-dipolar additions

Further reactions that are highly suited to the synthesis of cyclohexane derivatives, such as cycloaddition processes, 1,3-dipolar additions, and Diels-Alder cyclizations, have been used extensively. In the latter set, carbohydrate-based dienes or dienophiles have been employed and, in addition, intramolecular processes have provided highly suitable means of synthesizing complex polycyclic systems. 

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). 

Olefins reacted with 5-phenyl-l,2,4-dithiazole-3-thiones when irradiated to give 1,3-dithiolan derivatives, cyclohexene for example giving (150), which on acid hydrolysis unexpectedly gave (151). The m-fusion of the rings in (151) was established by its conversion into cyclohexene on treatment with triethyl phosphite. Olefins with electron-withdrawing substituents did not react with 5-phenyl-l,2,4-dithiazole-3-thione, suggesting that free-radical intermediates, and not 1,3-dipolar intermediates, were involved in the initial addition. The hitherto unknown l,3-dithiolan-4-thione system has been synthesized cyclohexane-1,1-dithiol reacted... 

Other successful asymmetric organocatalytic cycloadditions were developed in the last year, such as a three-component asymmetric 1,3-dipolar cycloaddition between aldehydes, amino esters and dipolarophiles, which was catalysed by a new biphosphoric acid derived from (i ,/ )-linked BINOL, furnishing multiply substituted pyrrolidines in high yields and with exeellent enantioselectivities of up to 99% ee. In addition, a new class of chiral bifunctional thiourea catalysts derived from traTO-2-amino-l-(diphenylphosphino)cyclohexane was applied to a highly enantioselective synthesis of a wide range of 2-aryl-2,5-dihydropyrrole derivatives on the basis of a [3 -b 2] cycloaddition between an A-phosphinoyl imine and an allene, providing high yields combined with excellent enantioselectivities of up to 98%. 

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