Asymmetric 1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides, Thiocarbonyl Ylides, and Nitrones

Sammanfattning: This thesis describes the development of methods for thepreparation of chiral non-racemic substituted pyrrolidines,tetrahydrothiophenes, and isoxazolidines. This has beenaccomplished by using asymmetric intermolecular 1,3-dipolarcycloaddition reactions of azomethine ylides, thiocarbonylylides and nitrones, respectively, with variousdipolarophiles.The asymmetry in these reactions was introduced using twodifferent approaches: a diastereoselective approach (i.e. usingdipolarophiles linked to chiral auxiliaries and/or usingenantiomerically pure ylides) and an enantioselective approach(i.e. the reacting partners are achiral and the reaction iscatalysed by an enantiomerically pure catalyst). Thus, usingthe former approach, 3,4-disubstituted pyrrolidines andtetrahydrothiophenes were obtained in high diastereofacialselectivities (up to 90:10 dr). Using the latter approach,bicyclic fused isoxazolidines were obtained in up to 93%ee.Some of the cycloadducts obtained from these reactions weretransformed into enantiopure known precursors of somebiologically active compounds{[(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol andoctahydrocyclopenta[c]pyrrol- 3a-ylmethylamine dihydrobromide}and an active stereoisomer of a sex pheromone component of apine sawfly [the acetate of (2S,3R,7R,9S)-3,7,9-trimethyl-2-tridecanol]. The synthetic utility of these1,3-dipolar cycloaddition reactions was also demonstrated bythe syntheses of some new enantiopure organocatalysts whichwere found to be useful in some 1,3-dipolar cycloadditionreactions of nitrones with a,b-unsaturated aldehydes.