TMP-zincate as highly chemoselective base for directed ortho metalation
TMP-zincate as highly chemoselective base for directed ortho metalation
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DOI：
10.1021/ja984263t
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发表时间：
1999-04-14
影响因子：
15
通讯作者：
Sakamoto, T
中科院分区：
文献类型：
--
作者：
Kondo, Y;Shilai, M;Sakamoto, T
自Gilman和Wittig的开创性工作以来，1定向邻位金属化反应已被广泛用作芳香族化合物的区域选择性官能化的强大而有效的方法。2各种导向基团已被用于促进芳烃的去质子化，并且各种强碱如烷基锂或二烷基氨基锂已被使用。酯基被认为是一个重要的和有吸引力的导向基团;然而，使用受到限制，因为去质子化需要严格控制的反应条件，由于中间芳基锂物种与酯官能团的不稳定性。为了开发一种新的功能化芳烃的化学选择性去质子化方法，我们研究了以新开发的二叔丁基四甲基哌啶锌酸锂（TMP-zincate）为碱的芳基锌酸盐的化学选择性形成。苯甲酸烷基酯的邻位金属化反应和缺π氮杂芳烃的直接R-金属化反应在室温下顺利进行，得到相应的芳基锌酸酯和杂芳基锌酸酯，并与亲电试剂反应。在众多的有机金属化合物中，有机锌试剂作为软亲核试剂在有机合成中得到了广泛的应用，通过各种方法活化的金属锌与有机卤化物进行氧化加成反应，成功地制备了具有功能基团的有机锌试剂。3我们最近报道了三烷基锌酸锂4可用作具有亲电官能团的芳基卤化物的卤素-金属交换反应的化学选择性金属化试剂。5具有酯基的芳基锌酸盐被认为比含酯的芳基锂更稳定，并且芳基金属物质的自缩合可以最小化。特别地，三叔丁基锌酸锂被发现是实际上有用的金属化剂，因为三有机锌酸盐中的叔丁基被发现在迁移偏好上落后于任何其他有机基团。5 b四甲基哌啶锂已被用于芳基羧酸酯的直接邻位锂化;然而，已知在金属化期间发生芳基锂和亲电子定向基团之间的不希望的缩合反应。6在芳基羧酸酯的去质子化过程中，亲电试剂原位捕获芳基锂的报道已经报道;然而，酯基的庞大性对于成功的去质子化-原位捕获是必不可少的。7
Since the pioneering work by Gilman and Wittig, 1 the directed ortho metalation reaction has been widely used as a powerful and efficient method for regioselective functionalization of aromatic compounds. 2 Various directing groups have been employed for facilitating the deprotonation of arenes, and various strong bases such as alkyllithiums or lithium dialkylamides have been employed. The ester group has been regarded as an important and attractive directing group; however, use has been limited because the deprotonation requires strictly controlled reaction conditions due to the instability of intermediary aryllithium species with the ester functionality. To develop a new chemoselective deprotonation of functionalized arenes, we investigated the chemoselective formation of arylzincates using newly developed lithium di-tert-butyltetramethylpiperidinozincate (TMP-zincate) as a base. The ortho metalation of alkyl benzoates and direct R-metalation of π-deficient aza-aromatics proceeded smoothly at room temperature to give the corresponding arylzincates and heteroarylzincates which reacted with electrophiles. Among various organometallics, organozinc reagents have been widely used as soft nucleophilic reagents in organic synthesis, and organozinc reagents with functional groups were successfully prepared by oxidative addition of organic halides to zinc metal activated by various methods. 3 We recently reported that lithium trialkylzincates4 can be used as chemoselective metalating reagents for the halogen-metal exchange reaction of aryl halides with electrophilic functional groups. 5 The arylzincates with ester groups are considered to be more stable than ester-containing aryllithiums, and self-condensation of the arylmetal species can be minimized. Especially, lithium tri-tert-butylzincate was found to be the practically useful metalating agent because the tert-butyl group in the triorganozincates was found to be behind any other organic groups in the migratory preference. 5bLithium tetramethylpiperidine has been used for directed ortho lithiation of arylcarboxylic esters; however, unwanted condensation reactions between the aryllithium and electrophilic directing groups have been known to occur during the metalation. 6 In situ trapping of the aryllithium by electrophiles during the deprotonation of the arylcarboxylic esters has been reported; however, the bulkiness of the ester group is essential for the successful deprotonation-in situ trapping. 7