Protecting Groups in Organic Synthesis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， 呼之即来，挥之即去。

挥之即去。

切莫请神容易， 切莫请神容易，送神难。

送神难。

羟基的保护基1). 酯类保护基 t-BuCO (Piv); PhCO; MeCO; ClCH2CO et al.OH HO OH OHPivCl (1eq) Py-CH2Cl2 0-25 oCHOOO90% Nicolaou, K. C.; Webber, S. E. 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, KBHEt3OTBDMS TBDMSO O O OTBDMSDIBAL(2.5eq) CH2Cl2, -78 oCTBDMSOOH95% Nicolaou, K. C.; Webber, S. E. Synthesis, 1986, 453ClCH2CO的去除可以用硫脲，氨/甲醇，苯，吡啶水溶液， NH2CH2CH2SH, NH2CH2CH2NH2, PhNHCH2CH2NH2 等除去。

O O O O O OBnClOBnOBn HOOBnOBnAcOOBnOBnNH2NH2 (15eq) HOAc-HOMe rt, 12 hAcO OOOBnOBnAcHNAcHNO OBn74% Cook, A. F.; Maichuk, D. T. J. Org. Chem., 1970, 35, 1940.OR AcO O RO O O O OR Ph O O O O H2NHN S SH HO AcOOH O O O O O OH Ph O O ODioxane, i-Pr2NEtAcOAcOR = ClCH2CO40%Smith, A.B.; Hale, K. J.; Vaccaro, H. A.; Rivero, R. A. J. Am. Chem. Soc, 1991, 113, 2112.2). 硅醚保护基 硅醚保护基主要有： Me3Si (trimethylsilyl, TMS); (triethylsilyl, TES); Et3Si 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, DBUOOHCO2Me COOBu-tO OTMS CO2MeMe3SiCl-Im 100 C, 90 min.oO O OH OTBSCOOBu-t O O O H OTBS100% Kerwin, S. M.; Paul, A. G.; Heathcock, C. H. J. Org. Chem., 1987, 52, 1686TES ether：TESCl/Imid. DMAP; TESOTf / Py. or 2,6-dimethylpyridineOH O H OTES OTESOTf (1.1eq) Py, MeCN, o -50 C, 10 min. 79%HHeathcook, C. H.; Young, S. D.; Hagen, J. P.; Pilli, R.; Badertscher, U. J. Org. Chem., 1985, 50, 2095TBDMS ether： TBDMSCl / imid. / DMF; TBDMSOTf / 2,6-dimethylpyridineOH OBz OBMP O OTBDMSOTf 2,6-di-tert-buylepyridine CH2Cl2, rt, 24 hOTBS OBz OBMP O OHikota, M.; Tone, H., Horita, K.; Yonemitsu, O. J. Org. Chem., 1990, 55, 7.OH OHOH OHDMF, rt,80%Nicolaou, K. C.; Pavia, M. R.; Seitz, S. P. J. Am. Chem. Soc., 1981, 103, 1224.imidazole(2.5 eq)DMF, rt, 48 hJ. Chem. Soc. Perkin. Trans. I , 1991, 1543.87%Marshell, J. A.; Sedrani, R. J. Org. Chem., 1991, 56, 5496.87%, 1989, 111, 2967.85%2MeOO Nakata, T.; Fukui, M.; Oishi, T. Tetrahedron Lett., 1988, 29, 2219.90%OHOTBSCollington, E. W.; Finch, H. Smith, I. J. Tetrahedron Lett., 1985, 26, 681.83%OFK-506, 73%Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L.J. Am. Chem. Soc., 1990, 112, 5583.reagent: PMBCl; p-MeOC 6H 4CH 2O-C(=NH)CCl 3 cleavage: DDQ, CANTr (三苯甲基醚) reagent: TrCl/Py/DMAP; TrOTf/2,6-dimethylpyridineclaevage: HCO 2H-H 2O; HCO 2H-tert -BuOH; HCl/MeCN; Na/NH 3tert -butyl (叔丁基醚) reagent: isopropene/CH 2Cl 2; t -BuO-C(=NH)CCl 3cleavage: HCO 2H; CF 3CO 2H; HBr-HOAc, FeCl 3; TiCl 4; TMSIallyl (烯丙基醚) reagent: Allyl bromidecleavage: t -BuOK/DMSO/NaOHcleavage : MOM HCl/THF/H 2O(1:2:1); Lewis acid: Me 3SiBr/CH 2Cl 2; Me 2BBr/CH 2Cl 2MTM AgNO 3/2,6-dimethylpyridine; HgCl 2/CaCO 3MEM ZnBr 2/CH 2Cl 2;HBr/THF;TiCl 4/CH 2Cl 2; MeBBr/CH 2Cl 2BOM Na/NH 3/EtOH, H 2/Pd(OH)2/C;Raney-Ni/EtOH;BF 3/PhSH/CH 2Cl 2 SEM HCl/MeOH; Lewis acid;THP(四氢吡喃) tetrahydropyrane etherreagents : DHP(3,4-dihydro-2H -pyran)cleavage : HOAc/THF/H 2O (4:2:1)Silylene derivatives(硅烯衍生物硅烯衍生物）DTBS (d i-tert-butylsilylene)reagent: t-Bu 2SiCl 2/Et 3N/HOBT/MeCN; (HOBT 1-hydroxybenzotriazole )t-Bu 2Si(OTf)2/2,6-dimethylpyridine/CH 2Cl 2Cleavage: HF-Py/THF-Pyridine, rtHO(CH 2)3OHp-TsOH91%Okawara, H.; Nakai, H.; Ohno, M. Tetrahedron lett., 1982, 23, 1087.J. A. J. Am. Chem. Soc., 1990, 112, 1607.HOCH 2CH 2OH TMSCl, rt, 16 hCO 2MeOOOO+ (TMS)2OChan, T. H.; Schwerdtfeger, A. E. J. Org. Chem., 1991, 56, 3294.76%Gerspacher, M.; Rapoport, H. J. Org. Chem., 1991, 56, 3700Me2Me2H2MeKOH (0.95 eq.)MeOH / H 2O95%Tetrahedron Lett., 1991, 22, 2679.Valerio, R. M.; Alewood, P. F.; Johns, R. B. Synthesis , 1988, 786.HOAc-i -PrOH-H 2OH2Me100%J. Org. Chem., 1990, 55, 3068.4:4:1100C, 15 hTsE (2-tosylethyl) Bn (benzyl)allyl (allyl) ester78-87%Org. Synthesis , 1988, Coll. Vol. VI, 418.2H BocO NPhCN80-83%Itoh, M.; Hagiwara, D.; Kamiya, T. Bull. Chem. Soc. Jpn ., 1977, 50, 718.rt, 3 hEt 3N, H 2O,dioxaneOO2 TFA100%Yamashiro, D.; Blake, J.; Li, C. H. J. Am. Chem. Soc., 1972, 94, 2855.NCOOMe CbzCOOMe 100%Sakaitani, M., Ohfune, Y. J. Org. Chem ., 1990, 55, 870.Et 3N, rt, 30 minEt 3SiH, PdCl 2Bergman, M.; Zervas, L. Ber. Deutsch. Chem. Ges., 1932, 65, 1192.N H 91%Hoogerhout, P.; Guis, C. P.; Erkelens, C.; van Boom, J. H.Recl. Trav. Chim. Pays-Bas , 1985, 104, 54.dioxane-H 2O, 0 o C, 4 h, rt. 8 h97%Schultheiss-Reimann, P.; Kunz, H. Angew. Chem. Int. Ed. Engl., 1983, 22, 62.CODcyclooctadiene CODcyclooctadiene Cp cyclopentadieneO SO 3H CSA camphorsulfonic acidCl NC DDQ 2,3-dichloro-5,6-dicyano -1,4-benzoquinone N N OC 2H 5O O C 2H 5O DEAD diethyl azodicarboxylate NIS N -iodosuccinimide O N N O O O DIAD diisopropyl azodicarboxylateoxideClCrO 3N O 3S PPTs pyridinium p -toluenesulfonate SO 3H PTS p -toluenesulfonic acid N Py pyridine TBAF tetrabutylammonium florideN F3ClS OCF 3DIBALH diisobutylaluminium hydride AlH DMAP4-N,N -dimethylaminopyridine N N DMF N,N -dimethylformamide DMPU N,N'-dimethylpropyleneurea 1,3-dimethyl-3,4,5,6-tetrahydro -2(1H)-pyrimidinoneN Im imidazol-1-yl LDA lithium diisopropylamide N NCS N -chlorosuccinimide N O Cl TFA trifluoroacetic acidO OH F F FF TIPSCl triisopropylsilyl chloride TIPSOTf triisopropylsilyl triflate Si O S O O F F F TMSBr trimethylsilyl bromide Si Br TMSCl trimethylsilyl chlorideSi ClO RuO 4Tr trityl triphenylmethyl Ph Bnbenzyl BOM benzyloxymethyl Cbz benzyloxycarbonyl O O Fmoc 9-fluorenylmethoxycarbonyl O Troc 2,2,2-trichloroethoxycarbonyl O O Cl Cl Cl辛烷99壬烷8。