药物合成反应第四章缩合反应.ppt

（3）影响因素thenatureofthecatalystisimportant,usuallyprimary,secondary,andtertiaryaminesandtheircorrespondingammoniumsalts,certainLewisacidscombinedwithatertiaryamine(e.g.,TiCl4/Et3N).theby-productofthereactioniswateranditsremovalfromthereactionmixturebymeansofazeotropicdistillation,theadditionofmolecularsieves,orotherdehydratingagentsshiftstheequilibriumtowardtheformationoftheproduct;thechoiceofsolventiscrucialandtheuseofdipolaraproticsolvents(e.g.,DMF)isadvantageous,sinceproticsolventsinhibitthelast1,2-eliminationstep;Stobbe反应反应通式反应机理Baldwin环化规则1Baldwin环化规则2SP3=tet；SP2=trig；SP=dig3SP3:5-6-endo禁阻4SP2:3-5-endo禁阻6其他允许5SP:3-4-exo禁阻影响因素onlyβ-arylethylamineswithelectron-donatingsubstituentsaffordhighyields;thereactionisusuallycarriedoutwithaslightexcessofthecarbonylcompound(toensurethecompleteconsumptionoftheamine)ineitherproticoraproticmedium;010302Strecker反应反应通式反应机理应用-Corey，1999第三节b-羟烷基、b-羰烷基化反应b-羟烷基化反应反应通式-F-C反应反应机理3.应用特点区域选择性苯环连在取代基多的C上立体选择性构型反转制备环内酯二、b-羰烷基化反应Michael加成反应反应机理:（3）影响因素thenucleophile(Michaeldonor)canbederivedbythedeprotonationofCH-activatedcompoundssuchasaldehydes,ketones,nitriles,β-dicarbonylcompounds,etc.aswellasbythedeprotonationofheteroatoms;dependingonthetypeandstrengthoftheelectron-withdrawinggroup(negativechargestabilizinggroup),theuseofevenrelativelyweakbasesispossible(e.g.,NEt3);应用第四节亚甲基化反应羰基烯化反应反应通式及机理影响因素theylidesarewateraswellasoxygen-sensitive；thephosphorousylideschemoselectivelyreactwithaldehydes(fast)andketones(slow),othercarbonylgroups(e.g.,esters,amides)remainintactduringthereaction;thestereoselectivity,E-orZ-selectivity,isinfluencedbymanyfactors:typeofylide,typeofcarbonylcompound,natureofsolvent；TheWittigreactionhasseveralimportantvarian