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-烯酸盐被有机铜试剂还原为相应的γ-氟-β、γ-烯酸盐。这种还原成功地应用于合成氟烯烃二肽同分异构体。在项目期间，我们发现了如下几个发现：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，还原-氧化烷基化工艺合成了α-取代氟烯烃二肽异构体3。SmI_2是代表性的单电子还原剂，也可用于合成氟烯烃二肽异构体4。在smi_2介导的γ、γ-二氟-α、β-烯酸盐、Sm（III）二烯酸盐等物质的还原过程中，可能涉及到这一看似合理的中间体的形成，并尝试了醛或酮对中间体的动力学捕获。结果表明，该动力学捕获方法可用于α-取代氟烯烃二肽同工异构体的合成

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