Dandapani Sivaraman, Curran Dennis P
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Org Chem. 2004 Dec 10;69(25):8751-7. doi: 10.1021/jo0488098.
First generation fluorous DEAD reagent bis(perfluorohexylethyl)azo dicarboxylate (C(6)F(13)(CH(2))(2)O(2)CN=NCO(2)(CH(2))(2)C(6)F(13), F-DEAD-1) has been shown to underperform relative to diisopropylazodicarboxylate in difficult Mitsunobu reactions involving hindered alcohols or less acidic pronucleophiles (phenols). Two new second generation fluorous reagents bearing propylene spacers instead of the ethylene spacers show expanded reaction scope while retaining the easy fluorous separation features. Byproducts from "half fluorous" reagent perfluorooctylpropyl tert-butyl azo dicarboxylate (C(8)F(17)(CH(2))(3)O(2)CN=NCO2(t)Bu, F-DEAD-2) can be removed by fluorous flash chromatography, and byproducts from bis(perfluorohexylpropyl)azo dicarboxylate (C(6)F(13)(CH(2))(3)O(2)CN=NCO(2)(CH(2))(3)C(6)F(13), F-DEAD-3) can be removed by fluorous solid-phase extraction. The new reagents promise to provide general and complementary solutions for separation problems in Mitsunobu reactions without restricting reaction scope.
第一代含氟DEAD试剂双（全氟己基乙基）偶氮二羧酸酯（C(6)F(13)(CH(2))(2)O(2)CN=NCO(2)(CH(2))(2)C(6)F(13)，F-DEAD-1）已被证明，在涉及受阻醇或酸性较弱的亲核试剂（酚类）的困难Mitsunobu反应中，其性能不如偶氮二异丙基羧酸酯。两种新型的第二代含氟试剂带有丙烯间隔基而非乙烯间隔基，在保留易于进行含氟分离特性的同时，展现出更广泛的反应范围。“半含氟”试剂全氟辛基丙基叔丁基偶氮二羧酸酯（C(8)F(17)(CH(2))(3)O(2)CN=NCO2(t)Bu，F-DEAD-2）产生的副产物可通过含氟快速柱色谱法去除，双（全氟己基丙基）偶氮二羧酸酯（C(6)F(13)(CH(2))(3)O(2)CN=NCO(2)(CH(2))(3)C(6)F(13)，F-DEAD-3）产生的副产物可通过含氟固相萃取法去除。这些新型试剂有望为Mitsunobu反应中的分离问题提供通用且互补的解决方案，同时不限制反应范围。
