Department of Chemistry, University of California , Berkeley, California 94720, United States.
J Am Chem Soc. 2013 Nov 27;135(47):17983-9. doi: 10.1021/ja409995w. Epub 2013 Nov 14.
We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.
我们报告了通过一种策略实现末端烯烃中烯丙基 C-H 键的对映选择性功能化，该策略包括通过 C-H 键功能化在末端碳原子上安装临时官能团，然后用广泛的试剂催化这种中间体的多样化。该方法包括钯催化的中性条件下的烯丙基 C-H 键氧化，形成线性烯丙基苯甲酸酯，然后是铱催化的烯丙基取代反应。这个整体转化过程以高支化选择性和优异的对映选择性（ee≤97%）形成各种含有新的 C-N、C-O、C-S 或 C-C 键的手性产物，产率良好。整体过程的广泛范围源于氧化和功能化步骤的分离；通过这样做，可以将亲核试剂的范围扩展到那些对直接氧化功能化敏感的亲核试剂。通过开发一种不需要酸的烯丙基氧化反应来形成具有高选择性的线性异构体，实现了整体过程的高对映选择性。这些烯丙基官能化过程适用于迭代序列，可得到具有催化剂控制的非对映选择性和对映选择性的（1，n）-官能化产物。该方法在生物活性分子的合成中的应用已经得到了证明。
