DEVELOPMENT OF ASYMMETRIC RADICAL REACTIONS AND APPLICATION TO THE SYNTHESIS OF BIO-ACTIVE COMPOUNDS

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1. DIASTEREOSELECTIVE RADICAL CYCLIZATION1) New chiral auxiliaries, trans-2-(N-benzenesulfonyl-N-benzylamino)cyclohexanol and its derivatives were developed and used for diastereoselective radical cyclization. When trans-2-(N- benzenesulfonyl-N-benzylamino)cyclohexyl 7-iodo-2,6-heptadienoate was reacted with nBu_3SnH in the presence of Et_3B and bulky Lewis acid, such as MAD, a diastereo mixture of (2- cyclopentenyl)acetate was obtained in 92% yield. After standard hydrolysis, (2-cyclopentenyl)acetic acid was obtained (53% ee) and the chiral auxiliary was recovered. Optically active (2- cyclopentenyl)acetic acid is a starting material for many biologically active compounds, such as coriolin, hirsutic acid C, and alepraic acid (a member of cyclopentenyl fatty acids).Optically active (2-cyclohexenyl)acetic acid (38% ee) was also obtained using the same auxiliary.2) Diastereoselective addition of tri-n-butyltin radical to chiral alpha, beta-unsaturated esters, having 8- phenylmenthyl grou … More p as a chiral auxiliary, was achieved in the presence of Lewis acid. Thus obtained beta-stannylester was converted to a chiral cyclopropane derivative.3) Chiral hydroxythiols, which were prepared from (R)-(+)-pulegone, were converted to chiral acetals, When the chiral acetals were irradiated using UV lamp in the presence of benzophenone, carbon radicals were generated and cyclized to chiral cyclopentane derivatives. Although diastereoselectivity was low, the reaction is a new method for the synthesis of chiral 2-substituted cyclopentanones.2. ENANTIOSELECTIVE RADICAL CYCLIZATIONWhen cyclohexyl 8-iodonona-2,8-dienoate was reacted with nBu_3SnH and Et_3B in the presence of chiral aluminum reagent, chiral (2-methylenecyclohexyl)acetate was obtained in 46% ee, This is the first example of enantioselective radical cyclization.3. NEW RADICAL SKELETAL REARRANGEMENT VIA ALKOXY RADICALThe radical reaction of epoxydecalin thiocarbonylimidazolide afforded rearranged bicyclic cyclooctanes. The reaction proceeded via ten-membered ring carbon radicals, which was generated by beta-cleavage of alkoxy radicals. This reaction is useful for some terpene synthesis having a cyclooctane ring. Less