有机合成中的保护基课件

1、Protecting Groups in Organic Synthesis,Nomenclature of Organic Compound-1,Nomenclature of Organic Compound-2,Nomenclature of Organic Compound-3,Abbreviation 1,Abbreviation 2,Abbreviation 3,Abbreviation 4,Abbreviation 5,Abbreviation 6,Abbreviation 7,Abbreviation 8,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

2、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。,羟基的保护基,1). 酯类保护基 t-BuCO (Piv); PhCO; MeCO; ClCH2CO et al. 90% Nicolaou, K. C.; Webber, S. E

3、. Synthesis, 1986, 453,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,

4、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

5、除去： （F-Si 142 kcal/mol; O-Si 112 kcal/mol） 通常用 HF / CH3CN; TBAF / THF; HF.Py / CH3CN,TMS ether：TMSCl or TMSOTf in pyridine, NEt3, i-Pr2NEt, imidazole, DBU,TES ether：TESCl/Imid. DMAP; TESOTf / Py. or 2,6-dimethylpyridine,TBDMS ether：TBDMSCl / imid. / DMF; TBDMSOTf / 2,6-dimethylpyridine,TBDPS ether：B

6、DPSCl / imid. / DMF, catalyst: DMAP, solvent: CH2Cl2,TIPS ether：TIPSCl / DMF / imidazole.,Cleavage,Cleavage,Cleavage,Cleavage,烷基醚类：,Me (甲基醚) reagent: MeI; (MeO)2SO2; MeOTf cleavage: TMSI/CH3Cl(CH2Cl or MeCN) or BBr3 / CH2Cl2 Bn (苄基醚) reagent: PhCH2Br or PhCH2Cl cleavage: H2 / 10% Pd/C, Raney-Ni, Rh-

7、Al2O3; Li(Na)/NH3 PMB (对甲氧基苄基醚); DMB or DMPB (3,4-二甲氧基苄基醚) reagent: PMBCl; p-MeOC6H4CH2O-C(=NH)CCl3 cleavage: DDQ, CAN Tr (三苯甲基醚) reagent: TrCl/Py/DMAP; TrOTf/2,6-dimethylpyridine claevage: HCO2H-H2O; HCO2H-tert-BuOH; HCl/MeCN; Na/NH3 tert-butyl (叔丁基醚) reagent: isobutene/CH2Cl2; t-BuO-C(=NH)CCl3 cle

8、avage: HCO2H; CF3CO2H; HBr-HOAc, FeCl3; TiCl4; TMSI allyl (烯丙基醚) reagent: Allyl bromide cleavage: t-BuOK/DMSO/NaOH,cleavage,烷氧基烷基醚：,MOM(甲氧基甲基醚) methoxymethyl ether MTM(甲硫基甲基醚) methylthiomethyl ether MEM(甲氧基乙氧基甲基醚) methoxyethoxymethyl ether BOM(苄氧基甲基醚) benzyloxymethyl ether SEM(三甲硅基乙氧基甲基醚) trimethyls

9、ilylethoxymethyl ether reagents: RCl or RBr/NaH/THF cleavage: MOM HCl/THF/H2O(1:2:1); Lewis acid: Me3SiBr/CH2Cl2; Me2BBr/CH2Cl2 MTM AgNO3/2,6-dimethylpyridine; HgCl2/CaCO3 MEM ZnBr2/CH2Cl2;HBr/THF;TiCl4/CH2Cl2; MeBBr/CH2Cl2 BOM Na/NH3/EtOH, H2/Pd(OH)2/C;Raney-Ni/EtOH; BF3/PhSH/CH2Cl2 SEM HCl/MeOH; L

10、ewis acid; THP(四氢吡喃) tetrahydropyrane ether 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-ketone Cleavage: Acid; Lewis acid Silylene derivatives(硅烯衍生物） DTBS (di-tert-butylsilylene) reagent: t-Bu2SiCl2/Et3N/HOBT/MeCN; (HOBT

11、 1-hydroxybenzotriazole) t-Bu2Si(OTf)2/2,6-dimethylpyridine/CH2Cl2 Cleavage: HF-Py/THF-Pyridine, rt,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, PPTs,Carboxylic acid：,1) Methyl ester Reagent: MeOH/HCl; MeOH/TMSCl; MeOH/SOCl2; MeI/KHCO3 Clea

12、vage: LiOH, KOH, NaOH/MeOH, THF,Carboxylic acid 3：,3) MOM (methoxymethyl), MEM (2-methoxyethoxymethyl), BOM (benzyloxymethyl), MTM (methylthiomethyl), SEM (2-trimethylsilyl ethoxymethyl) TCE (2,2,2-trichloroethyl) TMSE (2-trimethylsilylethyl) TsE (2-tosylethyl) Bn (benzyl) allyl (allyl) ester,Carboxylic acid 2,2) tert-butyl ester Reagent: isobutene/H2SO4 Cleavage: acetic acid/isopropanol; TFA/CH2Cl2,Amino group 1：,1) Boc (tert-butoxycarbonyl) Reagent: (Boc)2O; BocON (2-(tert- butoxycarbonyloxyimino)phenylacetonitrile) Cleavage: TFA; TFA/CH2Cl2,Amino group 2,2) Cbz (benzyloxy