The stereodivergent total synthesis of all stereoisomers of bioactive natural compounds to enable complete evaluation of stereochemical structure-activity relationships is highly challenging and valuable. Naturally occurring flavaglines, containing a compact functionalized cyclopenta[b]benzofuran scaffold, display a wide range of biological activities. Herein, we disclose a novel stereodivergent allylic alkylation of benzofuran-3(2H)-one that relies on the synergistic catalysis of a chiral N,N′-dioxide-Co(or Ni) complex and a phosphoramidite-Ir catalyst. All four possible stereoisomers of the α-allylated product are provided with excellent diastereo- and enantioselectivities by appropriate permutations of the two chiral catalysts. The concise synthesis of the targeted molecule rocaglaol is furnished in a stereodivergent manner, following a uniform synthetic route and using the same set of starting materials. Subsequently, a preliminary study on the anticancer activity for eight stereoisomers of rocaglaol reveals the pronounced influence of stereochemistry variations on biological activity.

生物活性天然化合物的所有立体异构体的立体发散全合成能够全面评估立体化学结构-活性关系是极具挑战性和价值的。含有紧凑的功能化环戊二烯[ b ]苯并呋喃支架的天然黄酮类化合物显示出广泛的生物活性。在此，我们公开了一种新的 benzofuran-3(2 H )-one 的立体发散烯丙基烷基化，它依赖于手性N的协同催化，N'-二氧化物-Co（或Ni）络合物和亚磷酰胺-Ir催化剂。通过两种手性催化剂的适当排列，α-烯丙基化产物的所有四种可能的立体异构体都具有优异的非对映选择性和对映选择性。目标分子罗卡劳酚的简明合成以立体发散的方式提供，遵循统一的合成路线并使用相同的起始材料组。随后，对八种罗卡劳酚立体异构体的抗癌活性的初步研究揭示了立体化学变化对生物活性的显着影响。