Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
J Am Chem Soc. 2022 Jul 13;144(27):11955-11960. doi: 10.1021/jacs.2c04195. Epub 2022 Jun 28.
Bicyclo[3.2.1] lactones are chemical scaffolds found in numerous bioactive natural products. Herein, we detail the development of a novel palladium(II)-catalyzed tandem intramolecular β-C(sp)-H olefination and lactonization reaction that rapidly transforms linear carboxylic acid possessing a tethered olefin into the bicyclo[3.2.1] lactone motif. This transformation features a broad substrate scope, shows excellent functional group compatibility, and can be extended to the preparation of the related seven-membered bicyclo[4.2.1] lactones. Additionally, we demonstrate the synthetic potential of this annulation by constructing the 6,6,5-tricyclic lactone core structure of the meroterpenoid cochlactone A. We anticipate that this compelling reaction may provide a novel synthetic disconnection that can be broadly applied toward the preparation of a variety of bioactive natural products.
双环[3.2.1]内酯是在许多生物活性天然产物中发现的化学支架。在此，我们详细介绍了一种新型钯 (II) 催化的串联分子内β-C(sp)-H 烯烃化和内酯化反应的发展，该反应可快速将带有侧链烯烃的线性羧酸转化为双环[3.2.1]内酯基序。这种转化具有广泛的底物范围，表现出优异的官能团兼容性，并可扩展到相关的七元双环[4.2.1]内酯的制备。此外，我们通过构建倍半萜 cochlactone A 的 6,6,5-三环内酯核心结构证明了这种环化反应的合成潜力。我们预计这种引人注目的反应可能提供一种新的合成断键，可以广泛应用于各种生物活性天然产物的制备。
