碳碳单键的形成反应-3

碳碳单键的形成反应-3有机过渡金属化学概念Concepts•配位化学Coordination Chemistry : The chemistry of transition metal complexes thathave noncarbon ligands (Werner complexes). Classification applies to the catalyst and all reaction intermediates.OR = O i PrAllylic alcoholt BuOOH概念Concepts•有机金属化学Organometallic Chemistry: The chemistry of metal complexes that have M-C bonds (organometallic complexes).Classification applies to the catalyst and/or reaction intermediates.Pd(PPh3)4catalyst有机过渡金属的重要性•Organotransition Metal Chemistry :Transition metal mediated reactions that solve (or have potential to solve) challenging problems in the synthesis of organic molecules.过渡金属碳碳单键的形成：过渡金属催化的偶联反应氧化加成还原消除转金属化常用的Pd催化剂与配体•常用的Pd催化剂有0价和+2价。

Pd(0): Pd(dba)2, Pd(PPh3)4Pd(II): Pd(OAc)2, PdCl2(MeCN)2, PdCl2等•常用的配体分为单齿(monodendate)和多齿(chelating)过渡金属价轨道与18电子规则18 electron rule: upper limit of 18 e-can be accomodated w/out using antibonding molecular orbitals (MO's).配位/解离与氧化加成•Oxidative Addition (OA):metal mediated breaking of a substrate σ-bond andformation of 1or 2 new M-L σ bonds. OA requiresremoval of 2 electrons from the metal's d electron count.This is reflected in a two unit increase in the metal'soxidation state.氧化加成•烯基卤代物和芳基卤代物与Pd的氧化加成速度很快；但烷基卤代物的加成速度慢，另外，如果氧化加成中间体在C-Pd键的β位有氢原子，易于发生消除反应生成烯烃，称为β –Η消除(β−Η elimination)。

过渡金属催化的偶联反应通常使用烯基卤代物或芳基卤代物烯基卤代物的制备方法MeCN/water碳碳单键的形成：过渡金属催化的偶联反应转金属化转金属化Transmetalation •Definition : the transfer of an organic group from one metal center to another. The process involves no formal change in oxidation state for either metal. Transmetalation is often a reversible process, with the equilibrium favoring the more ionic M-X bond .♣Subsequent reactivity of one L n M-R species can drive the equilibrium in one direction. This is often exploited in cross-coupling reactions,常用的转金属化试剂与相关反应In general, the rates of transmetalation of R follow the order: alkynyl> aryl,vinyl>alkyl还原消除Reductive Elimination •Reductive elimination is a key transformation in transition metal mediated catalysis, often representing the product forming step in a catalytic cycle.•Orbitals with more s character are less directional and lead to better overlap in the transition state for reductive elimination (RE). Note: cis orientation of the ligands is required for RE to occur.Negishi偶联：有机锌，有机铝，有机锆的偶联反应优点：官能团容忍性好Negishi偶联Negishi偶联Negishi偶联Negishi偶联：ZnNegishi偶联：ZnNegishi Coupling•The addition of ZnCl2increased the reactivity of the transmetalating reagent making the cross coupling of sterically hindered substratespossible. It is thought that the alkenylzirconium, alkenylalaneundergo in situ transmetalations with ZnCl2to form alkenylzinc, amore reactive transmetalating reagent.For Structure–Reactivity Relationships in Negishi Csp2-Csp2 Cross-Coupling Reactions, See: Chem. J. Eur. 2009, DOI: 10.1002/chem.200902132Suzuki偶联Suzuki偶联•硼试剂可以是三取代硼烷、硼酸、硼酸酯或氟硼酸盐Suzuki偶联：E式烯基硼制备Suzuki偶联：Z式烯基硼制备Suzuki偶联Suzuki偶联Suzuki偶联Suzuki偶联：Csp3-Csp2Suzuki偶联：Csp3-Csp3Stille偶联Stille偶联与金属锡相连基团在转金属化时的迁移速度是：Stille偶联Organotin Reagent:•Highly functional group tolerant•Readily synthesized via a variety of methods•Air and moisture stable (often distillable)•Stable to the vast majority of organic reagents.•Highly toxic!!!•β-hydride elimination can be a serious side reaction within alkyl palladium intermediates.•Oxidative addition and reductive elimination steps occur with retention of configuration for sp2-hybridized substrates.•Thus, Stille coupling is mainly used in sp2-sp2bonding.Stille偶联Heck反应Heck反应机理Synthetic Chemistry -Lecture 638Heck 反应•溶剂Solvents:Typically aprotic 通常用非质子溶剂; a range of polarities .•催化剂Catalyst:Pd(II) sources: Pd(OAc)2,PdCl 2PR 3, PdCl 2(CH 3CN)2Pd (0) sources: Pd(PPh 3)4, Pd(dba)2+ PR 3•碱Base: 2o or 3o amine, NaOAc, K 2CO 3, KHCO 3, KOAc The base may serve a dual purpose: reducing the Pd(II) precatalyst to Pd(0) and promoting reductive elimination of the PdH(X) intermediate by shifting the equilibrium towards Pd(0).TBAC添加剂降低反应温度保持烯烃反应物的立体化学TBAC添加剂•Jeffery conditions: the combination of tetraalkylammonium salts (phase-transfer catalysts) and insoluble bases accelerates the rate, so that lower reaction temperatures are possible.Jeffery, T. Tetrahedron 1996, 52, 10113–10130.•Explanation: Palladium complexes can be stabilized by the coordination of halide ions; thus, the catalyst is less likely to decompose under the Heck reaction conditions.J. Am. Chem. Soc. 1991, 113, 8375–8384区域选择性•RPdX中的R基团倾向于插入烯烃缺电子一端和位阻小的一端。