智能断句MOM(甲氧基甲基醚)是⼀种保护羟基的常⽤⽅法,在有机合成中具有重要的地位。它的基本优点是上保护容易,且产率较好;可在多条件下去保护,具有⼴泛的适⽤范围,其对酸还是较为稳定的,⼀般它的脱除需要在强酸条件下进⾏。 保护条件:
⼀、CH 3OCH 2Cl(MOMCl),DIEA,在⼆氯甲烷中,0℃到室温,反应8h,在引⼊MOM时,此条件是最常⽤的⽅法。但是MOMCl是致癌物,⽽且在制备MOMCl时产⽣的⼆氯甲基甲基醚毒性更强。因此在使⽤MOMCl时要做好防护措施。 MOM(CH 3 OCH 2 -OR) 羟基保护⽰例( J. Org. Chem. 1995, 60 ,7796)放大器的放大
To a stirred solution of (1) (51.0 g, 99 mmol) in CH 2 Cl 2 (1.0 L) at room temperature were successively added DIEA (51.5 mL, 0.297 mol) and MOMCl (15.0mL, 0.198 mol) over a 10 min period. Thesolution was stirred 11 h at room temperature after which a saturated aqueousNH 4 Cl solution (20
0 mL) was added. The aqueous phase was segregated, and the organic one was washed withwater (100 mL), brine (100 mL0, dried with anhydrous MgSO4, filtered, andconcentrated to give pure MOM ether (2) (55.3 g, 100%) (slightly yellowish oil).
⼆、利⽤MOMCl上保护时,对于位阻较⼤的羟基,有时在反应中会加⼊NaI促进反应。原位⽣成了MOMI增加了反应活性。
远程升级
三、CH2(OMe)2,DCM,TfOH,室温4h,产率65%。【J. Org. Chem.,57, 940(1992)】此⽅法使⽤于⽣成伯、仲、烯丙基和炔丙基的MOM醚。叔醇不能完全反应,1,3-⼆醇则⽣成亚甲基缩醛。
利⽤甲醛⼆甲缩醛上MOM的⽅法中,还有其他酸性催化的⽅法,如TsOH/LiBr,⽆⽔三氯化铁,五氧化⼆磷等等。 脱保护条件:
⼀、少量浓盐酸,甲醇,62℃,15min。
⼆、6M HCl, THF/H2O,50℃,5-8h。
电解抛光三、少量浓盐酸,异丙醇,加热。
To a stirred solution (1) (1.00 g, 1.45 mmol) in dry isopropylalcohol (10.0 mL) were added two drops (~0.06 mL) of concentrated aqueous hydrochloric acid. The solution was stirred at 55 o C for 10 h and although incomplete as indicated by TLC analysis, was allowed to cool to room temperature (prolonged reaction timestend to give substantial decomposition). A saturated aqueous NaHCO 3 (20 mL) and diethyl ether (50 mL)were added to the mixture. The phase wasseparated and the aqueous layer was extracted with diethyl ether (5 ´50 mL). The combined organic layer was washed with brine (10 mL), dried over MgSO 4 , filtered, and concentrated. The crude product was purified by flashchromatography to give (2) (0.63 g, 65%).
四、苯硫酚,⼄醚,98%产率。【 J. Am. Chem. Soc. , 100,1938(1978)】
五、PPTS(对甲苯磺酸吡啶盐),叔丁醇,回流80-90%产率。【 Synth. Commun., 13, 1021(1983)】 六、三氟⼄酸,⼆氯甲烷,产率85% 。【J. Am. Chem. Soc. , 103,3210(1981)】
七、⼄酰氯,甲醇,0℃,4天。
【 Tetrahedron , 55, 3855(1999)】
⼋、50%AcOH, 催化量硫酸,回流10-15分钟,80%收率。
可信的密封黏胶条
【 J. Am. Chem. Soc. , 55, 3040】
九、Me2SiCl2, TBAB, 4-A MS, DCM, 0℃, 6h,47%产率。
【 J. Org. Chem. , 62, 7908(1997)】
⼗、Me2BBr, DCM, -78℃,87-95%产率。
移动管式喷砂机
【 Tetrahedron Lett. , 24, 3969(1983)】
⼗⼀、TMSBr, DCM, -30℃,10min,-10℃,4h,93%产率。
【 J. Am. Chem. Soc. , 116, 1004】
⼗⼆、
【 J. Org. Chem. , 51, 635(1986)】
编辑⾃:Greene's Protective Groups in Organic Synthesis(Wuts & Greene, 4th Ed),P30-36.