D. A. Evans Cycloaddition Reactions-3 [2+2]: Stepwise Versus Concerted Ketene-Alkene[2+2 H R 一兮 least hindered Stepwise Concerted Very large polar effects E olefins yield a mixture of cis and trans Ketenes add stereoselectively to Z for support stepw than e Calculations(Wang and Houk show a highly synchronus transition state in the gas phase All stereochemical outcomes can be tionalized assuming a stepwise mechanism Frey, H M. Isaacs, NJ J. Chem soc.B,1970,830832 Solvent Effects Ketenes Aldehydes Afford p-Lactones ab initio calulations endolexo path A 38 kcal/mol cl hexane 4.3/1 Br hexane 0.71/1 Cl Et3N 2.2/1 Br Et3N 16/1 Br CH3CN 0. 14/1 CI CH3C 0.59/1 Solvent effects implicate a zwitterionic intermediate Brady, et al, JACS 1970, 92, 146-148 Pons. J. -M. et. al JAcs1997,119,333X Cl Cl Cl Cl H R H R C C O R' H C O Me X H R H R C R' H O Me X O X Br Br Br X Me O R' O R R O C H H O C Me Me O C Me Me C O Me Me Me Me Me Me Me Me C Me Me C Me H H Me O O O H H H H B O Me Me Me Me O Me Me Me Me A A C Me Me C H Me H Me O O Me Me Me Me B O H H O O H H H H O O D. A. Evans Cycloaddition Reactions-3 Chem 206 [2+2]: Stepwise Versus Concerted • Ketenes add stereoselectively to Z alkenes • Z olefins are much more reactive than E least hindered bond rotation • Very large polar effects • E olefins yield a mixture of cis and trans products • Solvent effects observed, but it could merely be a ground state effect • KIE seen for many reactions support stepwise mechanism • Calculations (Wang and Houk) show a highly asynchronus transition state in the gas phase reaction • All stereochemical outcomes can be rationalized assuming a stepwise mechanism Stepwise Concerted Solvent Effects + + endo exo Solvent hexane Et3N CHCl3 CH3CN endo / exo 4.3 / 1 2.2 / 1 1.6 / 1 0.59 / 1 Solvent hexane Et3N CH3CN endo / exo 0.71 / 1 0.28 / 1 0.14 / 1 • Solvent effects implicate a zwitterionic intermediate Brady,et. al, JACS 1970, 92, 146-148. Ketene-Alkene [2+2] + Fast 1 : 2 D D + + + _ + _ + Frey, H. M.; Isaacs, N. J. J. Chem Soc. B, 1970, 830-832. + 38 kcal/mol 32 kcal/mol Ketenes + Aldehydes Afford -Lactones path A path B ab initio Calulations Pons, J. -M.; et. al. JACS 1997, 119, 3333