Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
Discovery Chemistry, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ, 08543, USA.
Angew Chem Int Ed Engl. 2020 Jun 8;59(24):9594-9600. doi: 10.1002/anie.202000532. Epub 2020 Apr 1.
The use of chiral transient directing groups (TDGs) is a promising approach for developing Pd -catalyzed enantioselective C(sp )-H activation reactions. However, this strategy is challenging because the stereogenic center on the TDG is often far from the C-H bond, and both TDG covalently attached to the substrate and free TDG are capable of coordinating to Pd centers, which can result in a mixture of reactive complexes. We report a Pd -catalyzed enantioselective β-C(sp )-H arylation reaction of aliphatic ketones using a chiral TDG. A chiral trisubstituted cyclobutane was efficiently synthesized from a mono-substituted cyclobutane through sequential C-H arylation reactions, thus demonstrating the utility of this method for accessing structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is crucial for the observed enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity.
手性瞬态导向基团（TDG）的使用是开发 Pd 催化对映选择性 C(sp 3 )-H 活化反应的一种很有前途的方法。然而，该策略具有挑战性，因为 TDG 上的手性中心通常远离 C-H 键，并且与底物共价连接的 TDG 和游离的 TDG 都能够与 Pd 中心配位，这可能导致反应性配合物的混合物。我们报告了使用手性 TDG 进行的 Pd 催化的脂肪酮的对映选择性 β-C(sp 3 )-H 芳基化反应。通过顺序的 C-H 芳基化反应，从单取代环丁烷高效合成了手性三取代环丁烷，从而证明了该方法可用于从简单的起始原料获得结构复杂的产物。使用缺电子的吡啶酮配体对于观察到的对映选择性至关重要。有趣的是，使用不同的银盐可以反转对映选择性。
