| This thesis presents measurement of rate constants for the chalcogen group transfer in bimolecular substitution reactions with primary alkyl radicals using Barton's PTOC ester, and an asymmetric synthesis of (20S)-camptothecin and its analogs via (4+1) radical annulation reaction as a key step.; Second-order rate constants for chalcogen group transfer from representative organosulfur-, organoselenium-, and organotellurium compounds to octyl radicals have been determined in benzene. For the determination of rate constants, an indirect competition method using Barton's PTOC ester as the radical precursor was employed. The rate constants were calculated from the ratio of self-trapped products of the octyl radical to group transferred products, and known rate constant for self-trapping of the octyl radical: The yield of products were measured by {dollar}sp1{dollar}H NMR integrations after the irradiation of the reaction mixture with a 275-W sunlamp. As observed in rate constants for iodine atom transfers, the radical stabilization by electron-attracting groups increases the rate constant for group transfer. The rate constants for the chalcogen group transfers to a primary radical are comparable to those for the halogen atom transfers. For example, the rate constant for PhSe group transfer from PhSeCH{dollar}sb2{dollar}CO{dollar}sb2{dollar}Et is 1.0 {dollar}times{dollar} 10{dollar}sp5{dollar} (M{dollar}sp{lcub}-1{rcub}{dollar}s{dollar}sp{lcub}-1{rcub}{dollar}) and that of Br atom transfer from BrCH{dollar}sb2{dollar}CO{dollar}sb2{dollar}Et is 0.7 {dollar}times{dollar} 10{dollar}sp5{dollar}.; This thesis also reports an asymmetric synthesis of camptothecin and its analogs. Based on the (4+1) radical annulation, we revised the first generation racemic synthesis of camptothecin which was not practical because of the low yields in the final two steps. By Sharpless asymmetric dihydroxylation, the enantiomerically pure DE-fragment of camptothecin 100 (94% ee) was synthesized from cyclic enol ether 97. Optimization for N-alkylation selectivity was explored and the addition of lithium bromide proved to be efficient in the improvement of the N/O-alkylation ratio satisfactorily. After extensive model studies, we extended the (4+1) radical reaction to the synthesis of various camptothecin derivatives, and several polycyclic compounds such as indenoquinoline and indenoquinoxaline. |
