D A Evans, J.Johnson Rules for Ring Closure: SP3 Carbon Related Systems Chem 206 Tetrahedral Carbon Case 2: King, J.C.S. Chem. Comm, 1979, 1140 Endo cyclization modes that are disallowed ( n-endo-tet n=3→9) 8-endo-tet disfavored intermolecular endo X 8-endo-tet RXn exclusively The stereoelectronic requirement for a 180% X-C-Y bond angle is only met when the endo cyclization ring size reaches 9 or 10 members 9-endo-tet Case 1: Eschenmoser. Helvetica Chim Acta 1970. 53. 2059 SOzOMe borderline Conclusions 6-endo-tet disfavored Allowed endo cyclization modes will require transition state ring sizes of at least nine members Rxn excl i Intramolecular epoxidation has also been evaluated 8-endo-tet yclization exclusively intermolecular. However the exocyclic analog i disfavored n= 1: rXn exclusively intermolecular 6-exo-tet 0=s=0 Beak states that the conclusions made with carbol substitution also hold for oxygen atom transfer Rxn exclusively Beak, P(1992). Determinations of transition-state geometries by the endocyclic restriction test: mechanisms of substitution at nonstereogenic atoms ."Acc. chem. Res. 25: 215D. A. Evans, J. Johnson Rules for Ring Closure: SP3 Carbon & Related Systems Chem 206 Tetrahedral Carbon Endo cyclization modes that are disallowed (n-endo-tet, n = 3 9) C Y endo X X Y C(SP3 ) The stereoelectronic requirement for a 180° X–C–Y bond angle is only met when the endo cyclization ring size reaches 9 or 10 members. CX3 O S O O O S O CY3 CX3 O- S O O O S O CY3 Cyclization exclusively intermolecular. However the exocyclic analog is exclusively intramolecular NaH 6-endo-tet disfavored CX2 I O S O O O S O CY3 CX2 O- S O O O S O CY3 NaH 6-exo-tet favored Case 1: Eschenmoser, Helvetica Chim. Acta 1970, 53, 2059. Case 2: King, J.C.S. Chem. Comm., 1979, 1140. NMe2 Me O S O O NMe3 + O S O O _ 8-endo-tet disfavored Rxn exclusively intermolecular (lecture 2) Rxn exclusively intramolecular Rxn exclusively intermolecular NMe2 SO2OMe NMe3 + SO3 – 8-endo-tet disfavored Rxn exclusively intermolecular NMe2 SO2OMe NMe3 + SO3 – 84% intermolecular, 16% intramolecular 9-endo-tet borderline Conclusions Allowed endo cyclization modes will require transition state ring sizes of at least nine members. Cl O–OH O Cl CO2H O n n Intramolecular epoxidation has also been evaluated Beak, JACS 1991, 113, 6281. n = 1: rxn exclusively intermolecular n = 9: rxn is intramolecular 8-endo-tet disfavored Beak states that the conclusions made with carbon substitution also hold for oxygen atom transfer. •• •• Beak, P. (1992). “Determinations of transition-state geometries by the endocyclic restriction test: mechanisms of substitution at nonstereogenic atoms.” Acc. Chem. Res. 25: 215