Hu Pengfei, Snyder Scott A
Department of Chemistry, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Department of Chemistry, University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.
J Am Chem Soc. 2017 Apr 12;139(14):5007-5010. doi: 10.1021/jacs.7b01454. Epub 2017 Mar 29.
A rare element of high strain in molecules of natural origin is a 1,2-trans fusion of 5-membered rings within a [3.3.0]-bicycle, a motif present in (-)-presilphiperfolan-8-ol. This molecule also possesses a 1,3-trans stereochemical arrangement of substituents on one of its 5-membered rings, a pattern shared by a number of other terpenes. Herein, we disclose the first total synthesis of this highly strained target in 13 steps. The key operation is a Pd-catalyzed tandem cyclization that directly establishes the requisite 1,3-trans stereochemical arrangement on one ring while concurrently setting the stage for the controlled generation of the highly strained 1,2-trans ring fusion of the final architecture.
天然来源分子中一种罕见的高张力元素是[3.3.0]双环内五元环的1,2-反式稠合，这一结构单元存在于(-)-前硅叶perfolan-8-醇中。该分子在其一个五元环上还具有取代基的1,3-反式立体化学排列，许多其他萜类化合物也有这种结构模式。在此，我们首次通过13步反应完成了这种高张力目标分子的全合成。关键步骤是钯催化的串联环化反应，该反应直接在一个环上建立所需的1,3-反式立体化学排列，同时为最终结构中高张力的1,2-反式环稠合的可控生成奠定基础。
