Synthesis of 2′-substituted 4-bromo-2,4′-bithiazoles by regioselective cross-coupling reactions
Synthesis of 2′-substituted 4-bromo-2,4′-bithiazoles by regioselective cross-coupling reactions
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DOI：
10.1021/jo025661o
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发表时间：
2002-08-09
影响因子：
3.6
通讯作者：
Heuser, S
中科院分区：
文献类型：
--
作者：
Bach, T;Heuser, S
标题化合物(1)的合成是由易于获得的2,4-二溴噻唑(2)分两步完成的。在区域选择性Pd(0)催化的交叉偶联步骤中，化合物2被转化为多种2-取代的4-溴噻唑3（16例，产率65-85%）。烷基和芳基卤化锌作为亲核试剂引入烷基或芳基取代基。遵循Sonogashira方案实现烷基脱溴。碳原子C-4上的溴锂交换和随后的金属转化为锌或锡将4-溴噻唑3转化为碳亲核试剂，并与另一等价物2,4-二溴噻唑进行第二次区域选择性交叉偶联(2)。根岸交叉偶联得到了2′-烷基-4-溴-2,4′-双噻唑1a-g的高收率（88-97%）。2'-苯基-和2'-烷基-4-溴-2,4'-双噻唑1h-j的合成需要Stille交叉偶联，但不像根岸交叉偶联那样顺利（产率为58-62%）。标题化合物的总产率为38% -82%，是合成2,4'-双噻唑的通用构建块。
The synthesis of the title compounds (1) was achieved in two steps starting from readily available 2,4-dibromothiazole (2). In a regioselective Pd(0)-catalyzed cross-coupling step, compound 2 was converted into a variety of 2-substituted 4-bromothiazoles 3 (16 examples, 65-85% yield). Alkyl and aryl zinc halides were employed as nucleophiles to introduce an alkyl or aryl substituent. The Sonogashira protocol was followed to achieve an alkynyl-debromination. Bromo-lithium exchange at carbon atom C-4 and subsequent transmetalation to zinc or tin converted the 4-bromothiazoles 3 into carbon nucleophiles which underwent a second regioselective cross-coupling with another equivalent of 2,4-dibromothiazole (2). The Negishi cross-coupling gave high yields of the 2'-alkyl-4-bromo-2,4'-bithiazoles 1a-g (88-97%). The synthesis of the 2'-phenyl- and 2'-alkynyl-4-bromo-2,4'-bithiazoles 1h-j required a Stille cross-coupling that did not proceed as smoothly as the Negishi cross-coupling (58-62% yield). The title compounds which were accessible in total yields of 38-82% 82% are versatile building blocks for the synthesis of 2,4'-bithiazoles.