Schulich Faculty of Chemistry, Technion-Israel Institute of Technology , Technion City, Haifa 32000, Israel.
J Am Chem Soc. 2014 Jul 9;136(27):9548-51. doi: 10.1021/ja504089y. Epub 2014 Jun 26.
Organofluorine compounds have found extensive applications in various areas of science. Consequently, the development of new efficient and selective methods for their synthesis is an important goal in organic chemistry. Here, we present the first Suzuki cross-coupling reaction which utilizes dihalo compounds for the preparation of secondary alkyl fluorides. Namely, an unprecedented use of simple 1-halo-1-fluoroalkanes as electrophiles in C(sp(3))-C(sp(3)) and C(sp(3))-C(sp(2)) cross-couplings allows for the formal site-selective incorporation of F-group in the alkyl chain with no adjacent activating functional groups. Highly effective approach to the electrophilic substrates, 1-halo-1-fluoroalkanes, via iododecarboxylation of the corresponding α-fluorocarboxylic acids is also presented. The conceptually new route to organofluorides was used for the facile preparation of biomedically valuable compounds. In addition, we demonstrated that an asymmetric version of the developed reaction for the stereoconvergent synthesis of chiral secondary alkyl fluorides is feasible.
有机氟化合物在科学的各个领域都有广泛的应用。因此，开发新的高效和选择性的合成方法是有机化学的一个重要目标。在这里，我们提出了第一个利用二卤代化合物合成仲烷基氟化物的铃木交叉偶联反应。也就是说，前所未有的将简单的 1-卤代-1-氟代烷烃作为亲电试剂用于 C(sp(3))-C(sp(3))和 C(sp(3))-C(sp(2))交叉偶联，实现了在没有相邻活化官能团的情况下，在烷基链上进行形式上的选择性氟取代。还提出了一种通过相应的α-氟羧酸的碘代脱羧反应制备亲电底物 1-卤代-1-氟代烷烃的高效方法。这种有机氟化物的新概念路线已用于生物医学有价值的化合物的简便制备。此外，我们证明了开发的用于手性仲烷基氟化物立体汇聚合成的不对称版本的反应是可行的。
