Synthesis of Fluoroalkene Dipeptide Isosteres Using Organocopper Reagents

在非水解性磷酸氨基酸模拟物的合成研究过程中，我们发现γ，γ-二氟-α，β-烯酸酯被有机铜试剂还原为相应的γ-氟-β，γ-烯酸酯。该还原方法成功地应用于氟烯二肽异构体的合成。在项目期间，我们发现了几个发现，如下所示1。有机铜介导的还原似乎是通过单电子转移机制进行的。基于上述机理，提出了还原氧化烷基化合成α取代氟烯二肽异构体的方法。具有代表性的单电子还原剂SMI_2也适用于氟烯二肽异构体的合成。在SmI_2介导的γ，γ-二氟-α，β-烯酸酯的还原反应中，Sm(III)二烯酸酯可能参与了这一可能的中间体的形成，尝试了醛或酮对该中间体的动能捕获。这一动力学捕集过程可用于α取代的氟烯二肽异构体的合成

During the course of our synthetic study of nonhydrolyzabk phosphoamino acid mimetics, we found that γ,γ-difluoro-α,β-enoates were reduced to the corresponding γ-fluoro-β,γ-enoates by organocopper reagents. This reduction was successfully applied to the synthesis of fluoroalkene dipeptide isosteres. During the term of the project, we found several finding as shown below1. Organocoppermediated reduction seems to proceed via single electron transfer mechanism2. Based on the above mechanism, reductionoxidative alkylation procedure for the synthesis of α-substituted fluoroalkene dipeptide isosteres3. SmI_2, representative one-electron reducing agent, is also applicable to the synthesis of fluoroalkene dipeptide isosteres4. In the SmI_2mediated reduction of γ,γ-difluoro-α,β-enoates, Sm(III)dienolate spicies are likely to be involved Based on formation of this plausible intermediate, kinetitic trapping of the intermediate by aldehydes or ketones were attempted. And this kinetic trapping procedure is proved to be useful for the synthesis of α-substituted fluoroalkene dipeptide isosteres