D. A Evans, J. Johnson Rules for Ring Closure: SP Carbon Related Systems Chem 206 Digonal Cyclizations: Interesting EXamples EtN, Toluene, reflux Trost. J. Am. Chem. Soc. 1979 101. 1284 12h,65-70%1 Proposes E-olefin geometry, EZ>95: 5 5-exo-dig CO,Me 30-40 kcal'mol and caveats a Baldwin's Rules are an effective first line of analysis in evaluating the stereoelectronics of a given ring closure otbs 1)RCOCl a Baldwin's Rules have provided an important foundation for the 71% study of reaction mechanism studies between different modes of cyclization only R ve impemtatios on about relative rates and are not an absolute indicator of whether a process is"or disfavored Works for varying ring sizes and R groups acylnitriliur ion can also work as an electophile in a Friedel-Crafts a Structural modifications can dramatically affect the cyclization type of reaction mode; beware of imines and epoxides Livinghouse, Tetrahedron 1992, 48, 2209 Tet Trig Di Tet Trig Dig v√√D. A. Evans, J. Johnson Rules for Ring Closure: SP Carbon & Related Systems Chem 206 O CN MeO2C O CO2Me CN R R' O OH HO2C H H O Me OTBS Me N + C - OTBS Digonal Cyclizations: Interesting Examples N + C 5-exo-dig Et3N, Toluene, reflux 12 h, 65-70% y. O R ■ Trost, J. Am. Chem. Soc., 1979, 101, 1284. Proposes E-olefin geometry, E/Z > 95:5 : N O O R H Me 30-40 kcal/mol ? Hirsutic Acid C LiCH2NC; TBS-Cl 71% 1) RCOCl 2) AgBF4 86% ■ Livinghouse, Tetrahedron 1992, 48, 2209. 5-endo-dig Works for varying ring sizes and R groups; acylnitrilium ion can also work as an electophile in a Friedel-Crafts type of reaction R R' : Conclusions and Caveats ■ Baldwin's Rules are an effective first line of analysis in evaluating the stereoelectronics of a given ring closure ■ Baldwin's Rules have provided an important foundation for the study of reaction mechanism ■ Competition studies between different modes of cyclization only give information about relative rates, and are not an absolute indicator of whether a process is "favored" or "disfavored" ■ Structural modifications can dramatically affect the cyclization mode; beware of imines and epoxides EXO Tet Trig Dig ENDO 3 4 5 6 7 Tet Trig Dig X X X X X X X X