D.A. Evans. J. John Rules for Ring Closure: SP2 Carbon Related Systems Chem 206 Case 2: continued Apparent exceptions to disallowed 5-endo-trig cyclization process MeO2C CO, Me 5-endo-trig 0% MeO2C Filer, J. Am. chem. Soc. 1979. 44. 285 100% CO-Me CO2 Me RHC KOBu Control experiment: Intermolecular reaction favors conjugate addtion m人 R= aryl,R2=aryl, alkyl CO Me COmE Grigg, J. Chem. Soc., Chem. Commun. 1980, 648. Case 3: Does the illustrated i ketalization process NH2NH2 necessarily violate"the 65 CH2 OH)2 1)EtO-CCl, pyridine 2)NH2NH disfavored? 5-endo-trig 200C x 5-endo-trig 5-exo-trig Johnson, C D (1993). "Stereoelectronic effects in the formation of 5-and Acc. Chem. Res. 26 476-82D. A. Evans, J. Johnson Rules for Ring Closure: SP2 Carbon & Related Systems Chem 206 X NH2 MeO2C CO2Me HN HN MeO2C MeO2C CO2Me O 5-endo-trig 0% 5-exo-trig 100% CO2Me Me Me CO2Me Me H Ph N O H N Ph Ph OK O Ph OMe O Ph CO2Me HN NH2 HN NH O Ph Ph O NH H2N 100% Control experiment: Intermolecular reaction favors conjugate addtion. 1) EtO2CCl, pyridine 2) NH2NH2 65 5-exo-trig oC 200 oC 5-endo-trig 0% MeI X Apparent exceptions to disallowed 5-endo-trig cyclization process N O N OH N O N R 1HC CO2Me R 2 CO2Me HN CO2Me CO2Me R 1 HN CO2Me R 1 R CO2Me 2 R 2 Filer, J. Am. Chem. Soc. 1979, 44, 285. R 1 = aryl, R2 = aryl, alkyl + KOtBu 3:1 Grigg, J. Chem. Soc., Chem. Commun. 1980, 648. R R O O R R O (CH2OH)2 H + Does the illustrated ketalization process necessarily violate "the rules"? R R O (CH2OH)2 O OH R R HO H+ O OH R R HO + H+ –H2O O OH R R + R R O O 5-exo-tet 5-endo-trig disfavored ? favored ? ( )2 ( )2 ( )2 Case 2: continued... Case 3: Ph OMe O 65 oC HN NH O Ph Johnson, C. D. (1993). “Stereoelectronic effects in the formation of 5- and 6-membered rings: the role of Baldwin's rules.” Acc. Chem. Res. 26: 476-82. PhCH2NH2 NH2NH2 CH3CO2H NH2NH2