Christoforou Irene C, Koutentis Panayiotis A
Department of Chemistry, University of Cyprus, PO Box 20537, 1678 Nicosia, Cyprus.
Org Biomol Chem. 2006 Oct 7;4(19):3681-93. doi: 10.1039/b607442a. Epub 2006 Aug 29.
Regioselective palladium catalysed coupling reactions are achieved in good to high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4-carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and alkynyl)isothiazoles 3, 4, 6-9 from Stille couplings, 3-halo-5-(hetero/arylethynyl)isothiazoles 14-19 from Sonogashira and 5,5'-bi(3-chloroisothiazole-4-carbonitrile) (13) from an Ullmann type coupling. 3,5-Dibromoisothiazole-4-carbonitrile 2 is more reactive than the dichloroisothiazole-4-carbonitrile 1 and effective enough for Stille, Negishi and Sonogashira couplings. 5,5-Bi(3-chloroisothiazole-4-carbonitrile) (13) is prepared by a palladium catalysed Ullmann coupling from 3-chloro-5-iodoisothiazole-4-carbonitrile (11). A variety of 3-substituted isothiazoles (3-substituents = Cl, Br, OMs, OTs and OTf) are less reactive and fail to give successful Suzuki couplings at the isothiazole C-3 position. The 3-iodo-5-phenyl-isothiazole-4-carbonitrile (28), prepared via Sandmeyer iodination, participates successfully in Suzuki, Ullmann type, Stille, Negishi and Sonogashira coupling reactions. All products are fully characterized.
从3,5-二氯-或3,5-二溴异噻唑-4-腈1和2出发，通过区域选择性钯催化偶联反应可获得良好至高产率的产物，通过Stille偶联反应得到3-卤代-5-(杂环/芳基、烯基和炔基)异噻唑3、4、6 - 9，通过Sonogashira反应得到3-卤代-5-(杂环/芳基乙炔基)异噻唑14 - 19，通过Ullmann型偶联反应得到5,5'-联(3-氯异噻唑-4-腈)(13)。3,5-二溴异噻唑-4-腈2比二氯异噻唑-4-腈1更具反应活性，对Stille、Negishi和Sonogashira偶联反应足够有效。5,5-联(3-氯异噻唑-4-腈)(13)由钯催化的Ullmann偶联反应从3-氯-5-碘异噻唑-4-腈(11)制备。多种3-取代异噻唑(3-取代基 = Cl、Br、OMs、OTs和OTf)反应活性较低，无法在异噻唑C-3位成功进行铃木偶联反应。通过桑德迈尔碘化反应制备的3-碘-5-苯基异噻唑-4-腈(28)成功参与了铃木、Ullmann型、Stille、Negishi和Sonogashira偶联反应。所有产物均经过充分表征。
