D.A. Evans C versus O Enolate Reactivity the Hammond Postulate Chem 206 Question: Why do we generally show enolates reacting with electrophiles The Hammond Postulate is also relevant to this issue and is broadly at carbon as opposed to oxygen ? Let's begin the the discussion with an used to make qualitative statements about transition state structure I"As electrophile reactivity increases, the percentage of reaction at the Hammond. JACS 1955.77 334 more reactive acetyl chloride extreme reactions, one which is strongly endothermic and one which is strongly exothermic El(+)C/O Rxn Ratio Strongly Exothermic Reactio E(+) AH >20 kcal/mol A a The very reactive acid chloride gives almost exclusively the O-acylation Rxn Coordinate roduct while the less reactive methyl iodide affords the alternate C-alkylation product Hammond Postulate These results may be understood in the context of qualitative statements "For strongly exothermic reactions, the transition state T made by Hammond(The Hammond Postulate)and Hine(The Principle of Least Motion) ooks like reactant(s)e.g.B LAs applied to the enolate-electrophile reaction, for very exothermic reactions, e.g. the reaction with acetyl chloride, the transition state for the "As reactions become more exothermic, the favored reaction becomes. instance the electrophile heads for the site of highest electron dens The Principle of Least Motion: process will involve little enolate structural reorganization. Hence in that path which results in the least structural (electronic)reorganization. Carey& Sundberg: Part A; Chapter 4, pp217-220 for discussion of hammonds Postulate See Hine in Advances in Phys. Org. Chem. 1977, 15, 1-61 Based upon the above discussion draw a detailed mechanism for the protonation of cyclohexanone enolate Since the X-ray data clearly support the picture that resonance structure 1 best represents the enolate structure, highly reactive electrophiles will favor o-attack according to Hine s generalizationEnergy Rxn Coordinate O – O O–El O El Me C O Cl B Me I A O – B O A Carey & Sundberg: Part A; Chapter 4, pp217-220 for discussion of Hammond's Postulate H + Based upon the above discussion draw a detailed mechanism for the protonation of cyclohexanone enolate. ■ As applied to the enolate-electrophile reaction, for very exothermic reactions, e.g. the reaction with acetyl chloride, the transition state for the process will involve little enolate structural reorganization. Hence in this instance the electrophile heads for the site of highest electron density Hammond Postulate "For strongly exothermic reactions, the transition state T‡ looks like reactant(s) e.g. B." Strongly Exothermic Reactions DH ° > 20 kcal/mol T ‡ ■ In attempting to grasp the Hammond Postulate, let's consider two extreme reactions, one which is strongly endothermic and one which is strongly exothermic. The Hammond Postulate is also relevant to this issue and is broadly used to make qualitative statements about transition state structure. Since the X-ray data clearly support the picture that resonance structure 1 best represents the enolate structure, highly reactive electrophiles will favor O-attack according to Hine's generalization. 2 1 The Principle of Least Motion: "As reactions become more exothermic, the favored reaction becomes that path which results in the least structural (electronic) reorganization." ■ The very reactive acid chloride gives almost exclusively the O-acylation product while the less reactive methyl iodide affords the alternate C-alkylation product. These results may be understood in the context of qualitative statements made by Hammond (The Hammond Postulate) and Hine (The Principle of Least Motion) >> 1 << 1 El(+) C/O Rxn Ratio El(+) : – ■ "As electrophile reactivity increases, the percentage of reaction at the enolate oxygen increases." For example, consider the reactions of cyclo￾hexanone enolate with the two electrophiles, methyl iodide and the much more reactive acetyl chloride: Question: Why do we generally show enolates reacting with electrophiles at carbon as opposed to oxygen ?? Let's begin the the discussion with an observation: D. A. Evans C versus O Enolate Reactivity & the Hammond Postulate Chem 206 Hammond, JACS 1955, 77, 334 See Hine in Advances in Phys. Org. Chem. 1977, 15, 1-61