Sarah siska. C. A. Morales Crams rule Chem 206 Don cram: 1952 Among the 27 cited reactions whose stereoselection Cram's rule: "In reactions of the is predicted by Crams acyclic rule following type, that diastereomer will predominate which would be Rs formed by the approach of the hindered side of the double bond NH3CI then the rotational conformation mInol of the c-c bond is such that the Felkin (Felkin) double bond is flanked by the two Cram acyclic model least bulky groups attached to the Curtin, D.Y., Pollak, P 1. J. Am. Chem. Soc. 1951, 73, 992 adjacent asymmetric center. Ranking of steric bulk of a-substituents is somewhat arbitrary. Cram, D. J. Elhafez, F.A. A.J. Am. Chem. Soc. 1952, 74, 5828 Me NH3Cl due to the amino group's formation of a non-rigid"more adaptable"ion pair Basis for model Nu-M=RMgX, LAH one proposed transition state in the end, a suggestion of a chelate Nu-M RR=Ph RM= Me, Et RS RS RM Rs=H R=H. Ph Me Et edicted -MaB -Ma Br (Felkin product) selectivities ranging from 2: 1 to >4: 1, favoring Felkin product Features and Liabilities activated carbonyl considered Nu: to be largest group ■ Possib| e Pitfalls Low or unreported yields may result in misleading selectivitie Model based on qualitative assessment of steric bulk ■Bot steric repulsion Crams acyclic model is a convenient mnemonic that predicts Felkin between Rl and torsional effect products in a-alkyl or aryl aldehydes or ketones R not discussed not considered Cram. D. J. Elhafez F A.A. J. Am. chem. Soc. 1952. 74 5828Sarah Siska, C. A. Morales Cram's Rule Chem 206 R O M R O M O R RS RM RL RL RM RS RL RM RS R RS RM RL HO Nu R RS RM RL Nu OH RL RM RS R OH Nu Don Cram: 1952 Nu: Nu-M Cram, D. J.; Elhafez, F. A. A. J. Am. Chem. Soc. 1952, 74, 5828 predicted (Felkin product) (anti-Felkin product) Cram acyclic model torsional effects not considered Nu: activated carbonyl considered to be largest group steric repulsion between RL and R not discussed Features and Liabilities Cram's Rule: "In reactions of the following type, that diastereomer will predominate which would be formed by the approach of the entering group from the least hindered side of the double bond when the rotational conformation of the C–C bond is such that the double bond is flanked by the two least bulky groups attached to the adjacent asymmetric center." + 90° trajectory of nucleophile Nu-M = RMgX, LAH RL = Ph RM = Me, Et RS = H R = H, Ph, Me, Et Basis for Model selectivities ranging from 2:1 to >4:1, favoring Felkin product H N H Me Ph O MgBr NH H MgBr Ph O MgBr O Ph Me NH3Cl Me Me Ph p-tolyl OH NH3Cl Me Ph HO p-tolyl NH3Cl Nu: ■ Bottom Line Cram's acyclic model is a convenient mnemonic that predicts Felkin products in a-alkyl or aryl aldehydes or ketones. p-CH3C6H4MgBr Nu: Among the 27 cited reactions whose stereoselection is "predicted" by Cram's acyclic rule: Ranking of steric bulk of a-substituents is somewhat arbitrary: Me > NH3Cl due to the amino group's formation of a non-rigid "more adaptable" ion pair major (anti-Felkin) minor (Felkin) yield not reported Cram, D. J.; Elhafez, F. A. A. J. Am. Chem. Soc. 1952, 74, 5828 one proposed transition state: in the end, a suggestion of a chelate . . . Curtin, D. Y.; Pollak, P. I. J. Am. Chem. Soc. 1951, 73, 992 • Low or unreported yields may result in misleading selectivities • Model based on qualitative assessment of steric bulk + ■ Possible Pitfalls