第3次课羰基化合物a-烷基化-201002.pdfVIP

CHAPTER 2 （第3次课） α-Alkylation and Arylation of Carbonyl Compounds Jia-Rong Chen 2016-03-02 CHAPTER 2 2 羰基化合物的反应类型 3 烯醇体催化模式 4 2.1 INTRODUCTION Carbonyl compounds including ketones, aldehydes and carboxylic acid derivatives constitute a class of carbon acids, the acidity of which falls in the pKa range of 25 to 35 in dimethylsulfoxide (DMSO). To generate an enolate from a carbonyl substrate, a suitable base should be chosen to meet two criteria: 1. Adequate basicity to ensure the selective deprotonation process for enolate generation 2. A sterically hindered structure so that nucleophilic attack of this base on the carbonyl centers can be prevented. 5 2.1 INTRODUCTION 弱酸 烯醇化（碱选择） 6 2.1 INTRODUCTION The metal amide bases had enjoyed much popularity since the introduction of sterically more hindered bases 1-4. Advantages: most suitable and commonly used bases for carbonyl deprotonation. quite soluble in ethereal solvent systems. 7 2.2.3 Chelation-Enforced Intra-annular Chirality Transfer （配位型的环内不对称诱导） As illustrated in the equations in Scheme 2-11. A lithium-coordinated five-membered or six-membered ring fixes the orientation between the inducing asymmetric center and the enolate: 8 2.2.3.2 Prolinol-Type Chiral Auxiliaries