有機(jī)合成中的保護(hù)基-課件

ProtectingGroups

inOrganicSynthesis1PPT課件NomenclatureofOrganicCompound-12PPT課件NomenclatureofOrganicCompound-23PPT課件NomenclatureofOrganicCompound-34PPT課件Abbreviation15PPT課件Abbreviation26PPT課件Abbreviation37PPT課件Abbreviation48PPT課件Abbreviation59PPT課件Abbreviation610PPT課件Abbreviation711PPT課件Abbreviation812PPT課件選擇保護(hù)基的原則：(1)保護(hù)基的供應(yīng)來源，包括經(jīng)濟(jì)程度。(2)保護(hù)基團(tuán)必須能容易進(jìn)行保護(hù)，且保護(hù)效率高。(3)保護(hù)基的引入對化合物的結(jié)構(gòu)論證不致增加過量的復(fù)雜性，如保護(hù)中忌諱產(chǎn)生新的手性中心。(4)保護(hù)以后的化合物必須承受的起以后進(jìn)行的反應(yīng)和后處理過程。(5)保護(hù)基以后的化合物對分離、純化、各種層析技術(shù)要穩(wěn)定。(6)保護(hù)基團(tuán)在高度專一的條件下能選擇性、高效率地被除去。(7)去保護(hù)過程的副產(chǎn)物和產(chǎn)物能容易被分離。

呼之即來，揮之即去。

切莫請神容易，送神難。13PPT課件羥基的保護(hù)基1).酯類保護(hù)基t-BuCO(Piv);PhCO;MeCO;ClCH2COetal.90%

Nicolaou,K.C.;Webber,S.E.Synthesis,1986,45314PPT課件酯類保護(hù)基的除去(cleavage)

堿性條件下水解，水解能力：

t-BuCO(Piv)<PhCO<MeCO<ClCH2CO

常用的堿：K2CO3,NH3,NH2NH2,Et3N,i-Pr2NEtetal

去除Piv一般用較強(qiáng)的強(qiáng)堿體系，如KOH/H2O,LiAlH4,DIBAL,KBHEt3

15PPT課件ClCH2CO的去除可以用硫脲，氨/甲醇，苯，吡啶水溶液，NH2CH2CH2SH,NH2CH2CH2NH2,PhNHCH2CH2NH2等除去。16PPT課件17PPT課件2).硅醚保護(hù)基硅醚保護(hù)基主要有：

Me3Si(trimethylsilyl,TMS);Et3Si(triethylsilyl,TES);

t-BuMe2Si(tert-butyldimethylsilyl,TBDMSorTBS)i-Pr3Si(triisopropylsilyl,TIPS)t-BuPh2Si(tert-butyldiphenylsilyl,TBDPS)酸水解相對穩(wěn)定性:TMS(1)<TES(64)<TBDMS(20,000)<TIPS(700,000)<TBDPS(5,000,000)堿水解相對穩(wěn)定性:TMS(1)<TES(50)<TBDMS=TBDPS(20,000)<TIPS(100,000)硅醚保護(hù)基的除去：（F-Si142kcal/mol;O-Si112kcal/mol）通常用HF/CH3CN;TBAF/THF;HF.Py/CH3CN18PPT課件TMSether：

TMSClorTMSOTfinpyridine,NEt3,i-Pr2NEt,imidazole,DBU19PPT課件TESether：

TESCl/Imid.DMAP;TESOTf/Py.or2,6-dimethylpyridine20PPT課件TBDMSether：

TBDMSCl/imid./DMF;TBDMSOTf/2,6-dimethylpyridine21PPT課件TBDPSether：

BDPSCl/imid./DMF,catalyst:DMAP,solvent:CH2Cl222PPT課件TIPSether：

TIPSCl/DMF/imidazole.23PPT課件Cleavage

24PPT課件Cleavage25PPT課件Cleavage26PPT課件Cleavage27PPT課件烷基醚類：Me(甲基醚)reagent:MeI;(MeO)2SO2;MeOTf

cleavage:TMSI/CH3Cl(CH2ClorMeCN)orBBr3/CH2Cl2Bn(芐基醚)reagent:PhCH2BrorPhCH2Clcleavage:H2/10%Pd/C,Raney-Ni,Rh-Al2O3;Li(Na)/NH3PMB(對甲氧基芐基醚);DMBorDMPB(3,4-二甲氧基芐基醚)reagent:PMBCl;p-MeOC6H4CH2O-C(=NH)CCl3cleavage:DDQ,CANTr(三苯甲基醚)reagent:TrCl/Py/DMAP;TrOTf/2,6-dimethylpyridineclaevage:HCO2H-H2O;HCO2H-tert-BuOH;HCl/MeCN;Na/NH3tert-butyl(叔丁基醚)reagent:isobutene/CH2Cl2;t-BuO-C(=NH)CCl3cleavage:HCO2H;CF3CO2H;HBr-HOAc,FeCl3;TiCl4;TMSIallyl(烯丙基醚)reagent:Allylbromidecleavage:t-BuOK/DMSO/NaOH28PPT課件

cleavage29PPT課件烷氧基烷基醚：MOM(甲氧基甲基醚)methoxymethyletherMTM(甲硫基甲基醚)methylthiomethyletherMEM(甲氧基乙氧基甲基醚)methoxyethoxymethyletherBOM(芐氧基甲基醚)benzyloxymethyletherSEM(三甲硅基乙氧基甲基醚)trimethylsilylethoxymethyletherreagents:RClorRBr/NaH/THFcleavage:MOMHCl/THF/H2O(1:2:1);Lewisacid:Me3SiBr/CH2Cl2;Me2BBr/CH2Cl2MTMAgNO3/2,6-dimethylpyridine;HgCl2/CaCO3MEMZnBr2/CH2Cl2;HBr/THF;TiCl4/CH2Cl2;MeBBr/CH2Cl2

BOMNa/NH3/EtOH,H2/Pd(OH)2/C;Raney-Ni/EtOH;BF3/PhSH/CH2Cl2SEMHCl/MeOH;Lewisacid;THP(四氫吡喃)tetrahydropyraneetherreagents:DHP(3,4-dihydro-2H-pyran)

cleavage:HOAc/THF/H2O(4:2:1)30PPT課件O,O-Acetals(縮醛和縮酮）Reagents:Acetone;benzaldehyde,cyclo-ketoneCleavage:Acid;LewisacidSilylenederivatives(硅烯衍生物）DTBS(di-tert-butylsilylene)reagent:t-Bu2SiCl2/Et3N/HOBT/MeCN;(HOBT1-hydroxybenzotriazole)

t-Bu2Si(OTf)2/2,6-dimethylpyridine/CH2Cl2Cleavage:HF-Py/THF-Pyridine,rt31PPT課件醛酮的保護(hù)：O,O-acetals:1,3-dioxalane(5-numberring)and1,3-dioxane(6-numberring)Catalyst:p-TsOH,CSA,PPTs32PPT課件33PPT課件Carboxylicacid：1)MethylesterReagent:MeOH/HCl;MeOH/TMSCl;MeOH/SOCl2;MeI/KHCO3Cleavage:LiOH,KOH,NaOH/MeOH,THF34PPT課件Carboxylicacid3：3)MOM(methoxymethyl),MEM(2-methoxyethoxymethyl),BOM(benzyloxymethyl),MTM(methylthiomethyl),SEM(2-trimethylsilylethoxymethyl)TCE(2,2,2-trichloroethyl)TMSE(2-trimethylsilylethyl)TsE(2-tosylethyl)Bn(benzyl)allyl(allyl)ester

35PPT課件Carboxylicacid22)tert-butylesterReagent:isobutene/H2SO4Cleavage:aceticacid/isopropanol;TFA/CH2Cl236PPT課件Aminogroup1：1)Boc(tert-butoxycarbonyl)Reagent:(Boc)2O;BocON(2-(tert-butoxycarbonyloxyimino)phenylacetonitrile)Cleavage:TFA;TFA/CH2Cl237PPT課件38PPT課件Aminogr