| We have developed a novel method using intramolecular {dollar}rm Ssb{lcub}N{rcub}2spprime{dollar} O-cyclization for the diastereoselective construction of tetrahydrofuran derivatives. A cis-selectivity was dominant for the formation of 2,4-disubstituted tetrahydrofuran, while a trans-selectivity was usually the case for the formation of 2,5-disubstituted tetrahydrofurans. The combination of these two steric effects perfectly controlled the stereochemistry to provide 2,3,5-tri- and 2,2,3,5-tetrasubstituted tetrahydrofurans. The Z-olefin generally renders a higher selectivity than the corresponding E-olefin. A chair-like transition state, in which the substituent groups occupy the equatorial positions, was used to explain the stereoselectivity of this cyclization. This strategy has been successfully applied in the synthesis of a trans, threo, trans bistetrahydrofuran derivative, a C-2 symmetric central core system of many acetogenins.; The {dollar}rm Ssb{lcub}N{rcub}2spprime{dollar} strategy was also used in the diastereoselective synthesis 2,4-disubstituted pyrrolidine derivatives via N-cyclization. A cis-selectivity was also observed. In the construction of 2,5-disubstituted pyrrolidine derivatives, a seven-membered-ring {dollar}rm Ssb{lcub}N{rcub}2{dollar} cyclization product was primarily formed for the Z-olefin, and a moderate selectivity was observed for the {dollar}rm Ssb{lcub}N{rcub}2spprime{dollar} cyclization of E-olefin.; An attempt to use intramolecular {dollar}rm Ssb{lcub}N{rcub}2{dollar} cyclization of oxime to form a five-membered-ring nitrone at the less hindered side to the target of cocaine analog was unsuccessful. An E-2 elimination product was observed as the major one. During the investigation to improve the nucleophilicity of the nitrogen by using an N-H isoxazolidine as nucleophile, we failed to isolate this isoxazolidine intermediate in the process of an oxidative removal of pMB protecting group from the nitrogen. We isolated an isoxazoline derivative as the only product. Although we had difficulties to reduce isoxazoline to N-H isoxazolidine, the transformation of isoxazolidine to isoxazoline by mild oxidation is synthetically useful. This method was successfully applied in the enantioselective synthesis of isoxazoline nucleosides, which can not be easily achieved by other literature methods. |
