Das Jayabrata, Ali Wajid, Ghosh Animesh, Pal Tanay, Mandal Astam, Teja Chitrala, Dutta Suparna, Pothikumar Rajagopal, Ge Haibo, Zhang Xinglong, Maiti Debabrata
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, India.
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
Nat Chem. 2023 Nov;15(11):1626-1635. doi: 10.1038/s41557-023-01295-x. Epub 2023 Aug 10.
Transition metal catalysis plays a pivotal role in transforming unreactive C-H bonds. However, regioselective activation of distal aliphatic C-H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C-H bond in the presence of methyl C-H is underexplored. Here we show activation of a methylene C-H bond in the presence of methyl C-H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C-H bond activation. Computational studies suggest that reversible C-H activation is followed by β-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C-O cyclization, and subsequent β-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C-H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.
过渡金属催化在转化惰性碳氢键方面起着关键作用。然而，远程脂肪族碳氢键的区域选择性活化面临巨大挑战，尤其是在没有导向模板的情况下。在甲基碳氢键存在时亚甲基碳氢键的活化研究较少。在此，我们展示了在甲基碳氢键存在的情况下亚甲基碳氢键的活化以形成不饱和双环内酯。该方法能够逆转脂肪族碳氢键活化中的一般选择性。计算研究表明，可逆的碳氢键活化之后是β-氢消除，以生成钯配位的环烯烃，该环烯烃进行立体选择性的碳-氧环化，随后进行β-氢消除以提供双环不饱和内酯。通过含中到大环的酸的脱氢内酯化以及与烯烃和烯丙醇的碳氢键烯基化反应，突出了该反应的广泛适用性。该方法极大地简化了重要双环内酯的合成，这些双环内酯是天然产物以及药物活性分子的重要特征。
