In contrast with abundant methods for the asymmetric functionalization of alkyl radicals to generate stereogenic centres at reaction sites, catalytic enantioselective desymmetrizing functionalization of alkyl radicals for forging multiple stereocentres—including positions that are remote from the reaction sites—with both high enantio- and diastereoselectivity remains largely unexplored. The major challenge for such reactions is the high reactivity of open-shell alkyl radicals. Here, we describe a strategy to address this challenge: the use of Cu(ii) phosphate to immediately associate with the in situ-generated reactive alkyl radical species, creating a compact and confined chiral microenvironment for effective stereocontrol. With this strategy, we have developed a general and efficient catalytic enantioselective desymmetrizing functionalization of alkene-tethered 1,3-diols. It provides various tetrahydrofurans and analogues bearing multiple stereocentres with remarkably high levels of enantio- and diastereocontrol. Density functional theory calculations and mechanistic experiments revealed a reaction mechanism involving an enantiodetermining outer-sphere C–O bond formation step.

与大量的烷基自由基不对称官能化方法在反应位点生成立体异构中心相反，烷基自由基的催化对映选择性去对称化官能化可锻造多个立体中心（包括远离反应位点的位置），同时具有高对映选择性和非对映选择性很大程度上未开发。这种反应的主要挑战是开壳烷基的高反应性。在这里，我们描述了应对这一挑战的策略：使用Cu（ii磷酸酯以立即与原位生成的反应性烷基基团缔合，从而形成紧凑而密闭的手性微环境，以进行有效的立体控制。通过这种策略，我们已经开发出了一种通用且有效的烯键式1,3-二醇催化对映选择性脱对称官能化方法。它提供了带有多个立体中心的各种四氢呋喃和类似物，对映和非对映控制水平非常高。密度泛函理论计算和机理实验揭示了一种涉及对映体确定外球体C–O键形成步骤的反应机理。