Synthesis of Fluoroalkene Dipeptide Isosteres Using Organocopper Reagents

在合成非水解磷酸氨基酸模拟物的过程中，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。该还原反应成功地应用于氟烯烃二肽电子等排体的合成。在项目期间，我们发现了以下几个发现1。有机铜介导的还原似乎通过单电子转移机制进行2。基于上述机理，采用还原-氧化烷基化法合成了α-取代氟烯二肽电子等排体3. SmI_2是典型的单电子还原剂，也适用于合成氟烯烃二肽电子等排体4。在SmI_2催化还原γ，γ-二氟-α，β-烯酸酯的反应中，Sm（III）的二烯醇化物可能参与还原反应。该动力学捕获方法可用于α-取代氟烯烃二肽电子等排体的合成

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