Synthesis of 1,3-Dienes via Ligand-Enabled Sequential Dehydrogenation of Aliphatic Acids

摘要

1,3-Dienesare common scaffolds in biologically active naturalproducts as well as building blocks for chemical synthesis. Developingefficient methods for the synthesis of diverse 1,3-dienes from simplestarting materials is therefore highly desirable. Herein, we reporta Pd(II)-catalyzed sequential dehydrogenation reaction of free aliphaticacids via beta-methylene C-H activation, which enables one-stepsynthesis of diverse E,E-1,3-dienes. Free aliphaticacids of varying complexities, including the antiasthmatic drug seratrodast,were found to be compatible with the reported protocol. Consideringthe high lability of 1,3-dienes and lack of protecting strategies,dehydrogenation of aliphatic acids to reveal 1,3-dienes at the latestage of synthesis offers an appealing strategy for the synthesisof complex molecules containing such motifs.