提起保护基化学,什么Boc,Cbz,Fmoc,Alloc,TFAA等等立刻涌入脑海,这些都是胺的保护基。相较于胺基保护,羧酸很多时候也需要保护。常见的羧酸保护基有叔丁酯,甲酯,乙酯,苄酯,烯丙醇酯,还有三氯乙醇酯等等。叔丁酯用酸脱保护,甲酯/乙酯一般用碱脱保护,苄酯一般用氢解脱保护,烯丙醇酯可以用四三苯基膦钯搭配亲核试剂脱保护,三氯乙醇酯可以用锌粉搭配氯化铵还原脱保护。然而,当底物中有对酸,碱,氢解等条件敏感的基团存在时,或者当有多个羧酸存在需要选择性保护时,这个时候如果有温和的取代基存在,就会对整个路线有非常积极的意义。今天小编和大家分享一个羧酸保护基:三甲基硅乙醇酯,这类保护基可以用TBAF很温和的脱除保护,与叔丁酯,甲酯,乙酯,苄酯,烯丙醇酯,还有三氯乙醇酯有很好的兼容性。 ![](data:image/png;base64,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)
那么三甲基硅乙醇酯如何合成呢?小编做了总结,如下图所示:小编一直觉得插羰反应是一类很实用的方法,可以直接制备酰胺,制备醇,在这里,这个方法同样适用于三甲基硅乙醇酯的合成,除了卤素,类卤素如OTf也可以很好地进行插羰反应。羧酸直接制备三甲基硅乙醇酯是合成该类酯最常用的方法了,除了酯缩合,Mitsunobu反应也是很好的制备该类酯的策略之一。如果你手边有现成的酯,也就没有必要去做插羰反应或者水解再做酯了,这个时候,可以用NaH等强碱直接做酯交换,也能以良好到优秀的产率得到三甲基硅乙醇酯。 带着叔丁酯,甲酯,乙酯,苄酯,烯丙醇酯,还有三氯乙醇酯的情况下,用TBAF脱除三甲基硅乙醇酯,其它官能团兼容肯定是没问题的。那么脱除叔丁酯,甲酯,乙酯,苄酯,烯丙醇酯,还有三氯乙醇酯的时候,三甲基硅乙醇酯能否很好地保留呢?在这里小编也做了总结,如下图所示:不管是酸性体系,还是碱性体系,以及钯碳氢解体系,锌粉还原体系,以及四三苯基膦钯体系,都能很好地兼容,可以说是全能型的。
因此,大家在实际工作中,遇到羧酸需要保护时,可以尝试使用三甲基硅乙醇酯,说不定会有意想不到的好效果。
来自有机合成路线 |