FOLDING STRAIN STEREOCONTROL - DIASTEREOS ELECTIVITY IN RING-CLOSURE REACTION

Potentiality of diastereofacial selection in ring-closure reaction of the substrate with a stereogenic center in the acyclic chain is discus sed in terms of ''folding strain stereocontrol'', which implies that t he difference between total sums of the strain energy involved in the diastereomeric foldings in the transition state is determinative for t he diastereofacial selectivity. Firstly, elucidation of the concept is provided referring to the asymmetric induction in intermolecular reac tion and literature examples of remote diastereoselection in the ring- closure are briefly surveyed. Then, an account of our investigation di rected to generalization of the concept is described. The diastereosel ection in cyclization was studied with regard to the locational relati onship of the substituents as well as the other factores in the substr ates : alkyl- and oxy-substituted 2-(6'-trimethylsilylhex-4'-enyl)-cyc lohex-2-enones and alkyl-substituted ethyl 7-bromo-2-methylheptanoates . In the second substrates, the utilization of the oxy-substitutents a s a stereocontrolling group has been explored in connection with a ste reoselective synthesis of clerodane diterpenoid. Cyclization reaction of 5-methyl- or 5,6-dimethyl-8-trimethylsilyloctenals was also studied for the stereoselective synthesis of marine natural products. The fol ding strain stereocontrol is proved to influence diastereoselectivity of a ring-closure reaction to a greater extent than generally thought and the utility of stereoselective ring construction using this approa ch is emphasized.