PREPARATION AND ELECTROPHILIC TRAPPING OF 7-LITHIATED BENZOXAZOLES GENERATED VIA BENZYNE CYCLIZATION
PREPARATION AND ELECTROPHILIC TRAPPING OF 7-LITHIATED BENZOXAZOLES GENERATED VIA BENZYNE CYCLIZATION
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DOI：
10.1021/jo00135a031
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发表时间：
1982-01-01
影响因子：
3.6
通讯作者：
CAROON, JM
中科院分区：
文献类型：
--
作者：
CLARK, RD;CAROON, JM
用过量的正丁基锂（2.5equiv）在四氢呋喃-己烷溶液中于-20 ℃处理IV-新戊酰基-间氟苯胺（1），顺利地产生锂硫物种4（方案I）。加入各种亲电子试剂得到7-取代的2-叔丁基苯并恶唑7-10。间氟基团对邻位锂化的强大活化作用6是容易形成苯炔的重要特征。在相同的反应条件下，相应的IV-新戊酰基-间-溴苯胺以慢得多的速率转化为4，并且甚至在室温下12小时后，起始材料也没有完全消耗。因此，IV-新戊酰基-间溴苯胺的邻位锂化所需的条件与母体IV-新戊酰基苯胺大致相同。8将IV-（叔丁氧基羰基）-间氟苯胺（2）转化为7-锂化苯并恶唑5需要2.5当量叔丁基锂或在低温下用1当量正丁基锂和1.5当量叔丁基锂顺序处理。过量的正丁基锂不会影响这种转化。这与母体IV-（叔丁氧羰基）-苯胺的邻位锂化只能用叔丁基锂实现的报道雅阁。9向5中加入亲电试剂，得到加合物，其在温和的酸性处理后水解，得到7-取代的2-苯并恶唑啉酮11-14。由于2-苯并恶唑啉酮可以转化为氨基苯酚，因此该合成可以获得6-取代的2-氨基苯酚。这（6）韦克菲尔德，BJ“有机锂化合物的化学”;佩加蒙出版社：牛津，1974年;第39页。(7)通过TLC分析监测4的形成和N-新戊酰基-溴苯胺的消失。在12小时后，大量的起始材料剩余，并且注意到几种副产物的形成（可能来源于金属转移过程）。溴化合物转化为4的限速步骤最有可能是锂化反应，而不是消除LiBr，尽管这还没有得到严格的证明。(8)Führer，W.; Gschwend，H. W. J. Org. Chem. 1979，44，1133。Gschwend，HW; Rodriguez，H. R.组织反应1979年，第26、45页。(9)Muchowski，J. M.;韦努蒂湾C. J. Org. Chem. 1980，45，4798.
Treatment of IV-pivaloyl-m-fluoroaniline (1) with excess n-butyllithium (2.5 equiv) in tetrahydrofuran-hexane so-lution at-20 C smoothly generated the lithio species 4 (Scheme I). Addition of a variety of electrophiles gave the 7-substituted 2-tert-butylbenzoxazoles 7-10. The powerful activating effect of the m-fluoro group on the ortho lithiation6 is an important feature of the facile benzyne formation. Under the same reaction conditions, the corresponding IV-pivaloyl-m-bromoaniline was con-verted to 4 at a much slower rate, and even after 12 h at room temperature starting material was not completely consumed. 7 Thus, the IV-pivaloyl-m-bromoaniline ap-parently required approximately the same conditions for ortho lithiation as did the parentIV-pivaloylaniline. 8 Conversion of IV-(ferf-butoxycarbonyl)-m-fluoroaniline (2) to the 7-lithiated benzoxazole 5 required either 2.5 equiv of tert-butyllithium or sequential treatment with 1 equiv of n-butyllithium and 1.5 equiv oftert-butyllithium at low temperature. Excess n-butyllithium does not effect this transformation. This is in accord with the report that ortho lithiation of the parent IV-(tert-butoxycarbonyl)-aniline can be achieved only with tert-butyllithium. 9 Addition of electrophiles to 5 gave adducts which were hydrolyzed upon mild acidic workup to afford the 7-sub-stituted 2-benzoxazolinones 11-14. Since 2-benzoxazolinones can be converted to aminophenols, this synthesis gives access to 6-substituted 2-aminophenols. This (6) Wakefield, BJ “The Chemistry of Organolithium Compounds”; Pergamon Press: Oxford, 1974; p 39.(7) The formation of 4 and the disappearance of the N-pivaloyl-mbromoaniline were monitored by TLC analysis. After 12 h a considerable amount of starting material remained, and the formation of several by-products was noted (possibly derived from transmetalation processes). The rate-limiting step in the conversion of the bromo compound to 4 is most likely the ortholithiation rather than elimination of LiBr although this has not been rigorously demonstrated.(8) Führer, W.; Gschwend, H. W. J. Org. Chem. 1979, 44, 1133. Gschwend, HW; Rodriguez, H. R. Org. React. 1979, 26, 45.(9) Muchowski, J. M.; Venuti, M. C. J. Org. Chem. 1980, 45, 4798.