Sarah Siska. C. A. Morales Cornforth-1 Chem 206 Don Cram :1959 t Cornforth: 1959 ater effective bulk than oh argument based on importance of of Winstein, who compares the Rs polarization in transition state, and evidence relative tendency of groups to occupy the equator of selectivity in a-chlorocyclohexanone position on a cyclohexane ring O-M additions CH3>OSo2CgH4CH3-P>OCOCH3>OH where the dipoles are antiparallel, the polarization of the carbonyl group would be thec yclic model would predict the opposite product Cram acyclic model easiest, thereby lowering transition state e case of an a-heteroatom - a new model is Cornforth model instein. S. Holmes, N. J.J. Am. chem. so a modification of cram s rule for 1955,77,5562 a-substituents x Additions to a-Chloro Carbonyls ucleophile approaches from the back face M ROH 1)R-M RSR Et2O.70℃ 2) ACOH Cram chelate model predicted (anti-Felkin) (Felkin) Features 1)R-M activated carbonyl considered Nu: to be largest group 2)H3O 90° trajectory R-M A: B yield of A (%) CH3Mgl OH 11.5 CHaLi OMe m电可e expects groups OH, OR, OAc, NR2, NHAc to chelate as in Cram acyclic model torsional effects not considered The open-chain model s to systems which conti oups attached to asymmetric carbon of the starting material which re incapable of complexing with organometallic reagents Comforth. J W. Comfort R H. Mathew. KK J. Chem. Soc. 1959. 112 Cram, D J; Kopecky, K.R. J. Am. Chem. Soc. 1959, 81, 2748Sarah Siska, C. A. Morales Cornforth-1 Chem 206 Don Cram: 1959 R O M X RS RM/L R O M O Ph Ph X Me O Ph OR M Me Ph CH3MgI CH3Li A major Ph Ph X Me R' OH X OH OMe RL RM RS Ph Ph X Me HO R' B minor Nu: Methyl has greater effective bulk than OH; Cram cites "A-values" of Winstein, who compares the relative tendency of groups to occupy the equatorial position on a cyclohexane ring. CH3 > OSO2C6H4CH3 -p > OCOCH3 > OH The acyclic model would predict the opposite product in the case of an a-heteroatom -- a new model is needed! Cram acyclic model Cram chelate model Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748 "The open-chain model applies to systems which contain only groups attached to asymmetric carbon of the starting material which are incapable of complexing with organometallic reagents." Nu: + • expects groups OH, OR, OAc, NR2, NHAc to chelate 1) R'-M 2) H3O + R'-M A : B Winstein, S.; Holmes, N. J. J. Am. Chem. Soc. 1955, 77, 5562 nucleophile approaches from the back face Nu: 11.5 : 1 9 : 1 yield of A (%) 20 50 R O M R O M X O R Cl RS RL RL RS X RL RS R Cl RS RL HO R' R Cl RS RL R' OH X RL RS R OH Nu Cornforth: 1959 Nu: Cornforth model Cornforth, J. W.; Cornforth, R. H.; Mathew, K. K. J. Chem. Soc. 1959, 112 1) R'-M Et2O, -70 °C 2) AcOH • argument based on importance of polarization in transition state, and evidence of selectivity in a-chlorocyclohexanone additions • ". . . where the dipoles are antiparallel, the polarization of the carbonyl group would be easiest," thereby lowering transition state energy • a modification of Cram's rule for electronegative, non-chelating a-substituents X + predicted (Felkin) as in Cram acyclic model, torsional effects not considered Nu: activated carbonyl considered to be largest group Features 90° trajectory of nucleophile net dipole of molecule minimized (anti-Felkin) Additions to -Chloro Carbonyls