第五章 药物合成反应 重排反应 1.pptVIP

Example Eschenmoser-Claisen重排 Ireland-Claisen重排 The most useful of all Claisen rearrangements. The enolate may be trapped with TMSCl or the enolate may be used directly. The reaction works well with the free enolate and actually allows for a faster rearrangement that will occur at 25 °C (anion accelerated). Cope重排 Fischer indole synthesis Mechanism Example （5） Lossen Rearrangement Example 酮类化合物被过酸氧化，与羰基直接相连的碳链断裂，插入一个氧形成酯的反应称为拜耳-魏立格（Baeyer-Villiger)氧化重排。 + CH3COOOH CH3COOC2H5 40oC + CH3COOH 常用的过酸有： （1）一般过酸 + 无机强酸（H2SO4） （2）强酸的过酸 ：CF3COOOH （3）一般酸 + 一定浓度的过氧化氢（产生的过酸立即反应） （5）拜耳-魏立格氧化重排 反应机理 H+ O-O键断裂 -R′′COO- , -H+ R′重排 R3C- R2CH- , RCH2- CH3- 3. 从杂原子到碳原子的重排 Stevens重排 R1 = EWG = Ar, heteroaryl, COR, COOR, CN; Y= CH2, CHR, NH; base: NaH, KH, RLi, ArLi, RONa, ROK R4 = CH3, alkyl, allyl, benzyl,CH2COAr General fetures (1) the key intermediate of the rearrangement is the nitrogen- or sulfur ylide; (2) the R1 group has to be able to stabilize carbanions, so it is often an electron-withdrawing group; General fetures (3) depending on the nature of R1, the acidity of the adjacent C-H bond varies so the type of base used for the deprotonation must be chosen accordingly; (4) R2 and R3 groups of ammonium salts cannot contain a hydrogen at their β-position, since the Hofmann elimination may compete; (5) when the migrating group has a stereocenter, it is transferred with retention of configuration at the migrating terminus; (6) when R1=aryl or heteroaryl, the Sommelet-Hauser rearrangement becomes competitive; Example Sommelet-Hauser重排 Wittig重排 Example 4. s-键迁移重排 Claisen重排 （1）Claisen Rearrange 环状过渡态 烯丙基苯基醚 邻烯丙基苯酚 对烯丙基苯酚 互变异构 互变异构 环状过渡态 [3,3]?迁移 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? [3,3]?迁移 Example （2）Amino-Claisen Rearrangement This reaction occurs best when nitrogen is converted to the ammonium salt. (3) Thio-Claisen Rearrangement This reaction is often run with a reagent that will convert sulfur to oxygen following the reaction. An advant