有机合成中的保护基ppt课件.ppt

ProtectingGroupsinOrganicSynthesis 1 NomenclatureofOrganicCompound 1 2 NomenclatureofOrganicCompound 2 3 NomenclatureofOrganicCompound 3 4 Abbreviation1 5 Abbreviation2 6 Abbreviation3 7 Abbreviation4 8 Abbreviation5 9 Abbreviation6 10 Abbreviation7 11 Abbreviation8 12 选择保护基的原则 1 保护基的供应来源 包括经济程度 2 保护基团必须能容易进行保护 且保护效率高 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 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 5 保护基以后的化合物对分离 纯化 各种层析技术要稳定 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 7 去保护过程的副产物和产物能容易被分离 呼之即来 挥之即去 切莫请神容易 送神难 13 羟基的保护基 1 酯类保护基t BuCO Piv PhCO MeCO ClCH2COetal 90 Nicolaou K C Webber S E Synthesis 1986 453 14 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 Pr2NEtetal去除Piv一般用较强的强碱体系 如KOH H2O LiAlH4 DIBAL KBHEt3 15 ClCH2CO的去除可以用硫脲 氨 甲醇 苯 吡啶水溶液 NH2CH2CH2SH NH2CH2CH2NH2 PhNHCH2CH2NH2等除去 16 17 2 硅醚保护基硅醚保护基主要有 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 Si142kcal mol O Si112kcal mol 通常用HF CH3CN TBAF THF HF Py CH3CN 18 TMSether TMSClorTMSOTfinpyridine NEt3 i Pr2NEt imidazole DBU 19 TESether TESCl Imid DMAP TESOTf Py or2 6 dimethylpyridine 20 TBDMSether TBDMSCl imid DMF TBDMSOTf 2 6 dimethylpyridine 21 TBDPSether BDPSCl imid DMF catalyst DMAP solvent CH2Cl2 22 TIPSether TIPSCl DMF imidazole 23 Cleavage 24 Cleavage 25 Cleavage 26 Cleavage 27 烷基醚类 Me 甲基醚 reagent MeI MeO 2SO2 MeOTfcleavage TMSI CH3Cl CH2ClorMeCN orBBr3 CH2Cl2Bn 苄基醚 reagent PhCH2BrorPhCH2Clcleavage H2 10 Pd C Raney Ni Rh Al2O3 Li Na NH3PMB 对甲氧基苄基醚 DMBorDMPB 3 4 二甲氧基苄基醚 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 NaOH 28 cleavage 29 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 苄氧基甲基醚 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 CH2Cl2BOMNa NH3 EtOH H2 Pd OH 2 C Raney Ni EtOH BF3 PhSH CH2Cl2SEMHCl MeOH Lewisacid THP 四氢吡喃 tetrahydropyraneetherreagents DHP 3 4 dihydro 2H pyran cleavage HOAc THF H2O 4 2 1 30 O O Acetals 缩醛和缩酮 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 rt 31 醛酮的保护 O O acetals 1 3 dioxalane 5 numberring and1 3 dioxane 6 numberring Catalyst p TsOH CSA PPTs 32 33 Carboxylicacid 1 MethylesterReagent MeOH HCl MeOH TMSCl MeOH SOCl2 MeI KHCO3Cleavage LiOH KOH NaOH MeOH THF 34 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 35 Carboxylicacid2 2 tert butylesterReagent isobutene H2SO4Cleavage aceticacid isopropanol TFA CH2Cl2 36 Aminogroup1 1 Boc tert butoxycarbonyl Reagent Boc 2O BocON 2 tert butoxycarbonyloxyimino phenylacetonitrile Cleavage TFA TFA CH2Cl2 37 38 Aminogroup2 2 Cbz benzyloxyc