Synthesis of 1,3-Dienes via Ligand-Enabled Sequential Dehydrogenation of Aliphatic Acids
Guangrong Meng, Liang Hu, Hau Sun Sam Chan, Jennifer X. Qiao, Jin‐Quan Yu
Abstract
1,3-Dienes are common scaffolds in biologically active natural products as well as building blocks for chemical synthesis. Developing efficient methods for the synthesis of diverse 1,3-dienes from simple starting materials is therefore highly desirable. Herein, we report a Pd(II)-catalyzed sequential dehydrogenation reaction of free aliphatic acids via β-methylene C–H activation, which enables one-step synthesis of diverse E,E -1,3-dienes. Free aliphatic acids of varying complexities, including the antiasthmatic drug seratrodast, were found to be compatible with the reported protocol. Considering the high lability of 1,3-dienes and lack of protecting strategies, dehydrogenation of aliphatic acids to reveal 1,3-dienes at the late stage of synthesis offers an appealing strategy for the synthesis of complex molecules containing such motifs.