有机合成中的保护基.ppt

Protecting Groups in Organic SynthesisNomenclature of Organic Compound-1Nomenclature of Organic Compound-2Nomenclature of Organic Compound-3Abbreviation 1Abbreviation 2Abbreviation 3Abbreviation 4Abbreviation 5Abbreviation 6Abbreviation 7Abbreviation 8选择保护基的原则：l(1)保护基的供应来源，包括经济程度。l(2)保护基团必须能容易进行保护，且保护效率高。l(3)保护基的引入对化合物的结构论证不致增加过量的复杂性，如保护中忌讳产生新的手性中心。l(4)保护以后的化合物必须承受的起以后进行的反应和后处理过程。l(5)保护基以后的化合物对分离、纯化、各种层析技术要稳定。l(6)保护基团在高度专一的条件下能选择性、高效率地被除去。l(7)去保护过程的副产物和产物能容易被分离。l 呼之即来，挥之即去。呼之即来，挥之即去。l l 切莫请神容易，送神难。切莫请神容易，送神难。羟基的保护基羟基的保护基l1).酯类保护基lt-BuCO(Piv);PhCO;MeCO;ClCH2CO et al.90%Nicolaou,K.C.;Webber,S.E.Synthesis,1986,453l酯类保护基的除去(cleavage)碱性条件下水解，水解能力：t-BuCO(Piv)PhCO MeCO ClCH2CO 常用的碱：K2CO3,NH3,NH2NH2,Et3N,i-Pr2NEt et al 去除Piv一般用较强的强碱体系，如 KOH/H2O,LiAlH4,DIBAL,KBHEt3 ClCH2CO的去除可以用硫脲，氨/甲醇，苯，吡啶水溶液，NH2CH2CH2SH,NH2CH2CH2NH2,PhNHCH2CH2NH2 等除去。2).硅醚保护基硅醚保护基主要有：Me3Si (trimethylsilyl,TMS);Et3Si (triethylsilyl,TES);t-BuMe2Si(tert-butyldimethylsilyl,TBDMS or TBS)i-Pr3Si (triisopropylsilyl,TIPS)t-BuPh2Si (tert-butyldiphenylsilyl,TBDPS)酸水解相对稳定性:TMS(1)TES(64)TBDMS(20,000)TIPS(700,000)TBDPS(5,000,000)碱水解相对稳定性:TMS(1)TES(50)TBDMS=TBDPS(20,000)TIPS(100,000)硅醚保护基的除去：（F-Si 142 kcal/mol;O-Si 112 kcal/mol）通常用 HF/CH3CN;TBAF/THF;HF.Py/CH3CNTMS ether：TMSCl or TMSOTf in pyridine,NEt3,i-Pr2NEt,imidazole,DBUTES ether：TESCl/Imid.DMAP;TESOTf/Py.or 2,6-dimethylpyridineTBDMS ether：TBDMSCl/imid./DMF;TBDMSOTf /2,6-dimethylpyridineTBDPS ether：BDPSCl/imid./DMF,catalyst:DMAP,solvent:CH2Cl2TIPS ether：TIPSCl/DMF/imidazole.Cleavage CleavageCleavageCleavage烷基醚类：烷基醚类：lMe(甲基醚)l reagent:MeI;(MeO)2SO2;MeOTf l cleavage:TMSI/CH3Cl(CH2Cl or MeCN)or BBr3/CH2Cl2lBn(苄基醚)l reagent:PhCH2Br or PhCH2Cll cleavage:H2/10%Pd/C,Raney-Ni,Rh-Al2O3;Li(Na)/NH3lPMB(对甲氧基苄基醚);DMB or DMPB(3,4-二甲氧基苄基醚)l reagent:PMBCl;p-MeOC6H4CH2O-C(=NH)CCl3l cleavage:DDQ,CANlTr(三苯甲基醚)l reagent:TrCl/Py/DMAP;TrOTf/2,6-dimethylpyridinel claevage:HCO2H-H2O;HCO2H-tert-BuOH;HCl/MeCN;Na/NH3 tert-butyl(叔丁基醚)l reagent:isobutene/CH2Cl2;t-BuO-C(=NH)CCl3l cleavage:HCO2H;CF3CO2H;HBr-HOAc,FeCl3;TiCl4;TMSIlallyl(烯丙基醚)l reagent:Allyl bromidel cleavage:t-BuOK/DMSO/NaOH cleavage烷氧基烷基醚：烷氧基烷基醚：lMOM(甲氧基甲基醚)methoxymethyl etherlMTM(甲硫基甲基醚)methylthiomethyl etherlMEM(甲氧基乙氧基甲基醚)methoxyethoxymethyl etherlBOM(苄氧基甲基醚)benzyloxymethyl etherlSEM(三甲硅基乙氧基甲基醚)trimethylsilylethoxymethyl etherl reagents:RCl or RBr/NaH/THFl cleavage:MOM HCl/THF/H2O(1:2:1);Lewis acid:Me3SiBr/CH2Cl2;Me2BBr/CH2Cl2l MTM AgNO3/2,6-dimethylpyridine;HgCl2/CaCO3l MEM ZnBr2/CH2Cl2;HBr/THF;TiCl4/CH2Cl2;MeBBr/CH2Cl2 l BOM Na/NH3/EtOH,H2/Pd(OH)2/C;Raney-Ni/EtOH;l BF3/PhSH/CH2Cl2l SEM HCl/MeOH;Lewis acid;lTHP(四氢吡喃)tetrahydropyrane ether l reagents:DHP(3,4-dihydro-2H-pyran)cleavage:HOAc/THF/H2O(4:2:1)O,O-Acetals(缩醛和缩酮）Reagents:Acetone;benzaldehyde,cyclo-ketoneCleavage:Acid;Lewis acidSilylene derivatives(硅烯衍生物硅烯衍生物）DTBS(di-tert-butylsilylene)reagent:t-Bu2SiCl2/Et3N/HOBT/MeCN;(HOBT 1-hydroxybenzotriazole)t-Bu2Si(OTf)2/2,6-dimethylpyridine/CH2Cl2Cleavage:HF-Py/THF-Pyridine,rt醛酮的保护：醛酮的保护：O,O-acetals:1,3-dioxalane(5-number ring)and 1,3-dioxane(6-number ring)Catalyst:p-TsOH,CSA,PPTsCarboxylic acid：l1)Methyl esterl Reagent:MeOH/HCl;MeOH/TMSCl;MeOH/SOCl2;MeI/KHCO3l Cleavage:LiOH,KOH,NaOH/MeOH,THFCarboxylic acid 3：l3)MOM(methoxymethyl),l MEM(2-methoxyethoxymethyl),l BOM (benzyloxymethyl),l MTM(methylthiomethyl),l SEM (2-trimethylsilyl ethoxymethyl)l TCE(2,2,2-trichloroethyl)l TMSE(2-trimethylsilylethyl)l TsE (2-tosylethyl)l Bn (benzyl)l allyl(allyl)ester Carboxylic acid 2l2)tert-butyl esterl Reagent:isobutene/H2SO4l Cleavage:acetic acid/isopropanol;TFA/CH2Cl2Amino group 1：1)Boc(tert-butoxycarbonyl)lReagent:(Boc)2O;l BocON(2-(tert-butoxycarbonyloxyimino)phenylacetonitrile)lCleavage:TFA;TFA/CH2Cl2Amino group 22)Cbz(benzyloxycarbonyl)Bergman(1932)reagent:CbzCl/base cleavage:catalytic hydrogenationAmino group 3：l3)Fmoc(9-fluorenylmethoxycarbonyl)l reagent:Fmoc-Cl/NaHCO3lCleavage:NH3,Et2NH,piperidine,morpholine