Synthesis of Lactones and Amino Acids via Reductive Carboxylation Reactions

这项赠款提案的目标是开发多组分和/或多步偶联反应，将二氧化碳作为关键组分来合成复杂的有机分子。我们证明了1，1-二氟烯烃可以很好地通过氟羧化反应生成α-三氟甲基羧酸。该合成方法优于以往的方法，因为我们能够缩短合成路线以获得这些有价值的分子，并且避免了昂贵的氟化试剂的使用。此外，我们还开发了在铜和银催化下的炔丙醇和胺的还原羧化反应，以较高的产率提供了γ-内酯和内酰胺类化合物。这种转化的关键是使用红铝作为还原剂，可以通过远端的跨金属水合过程提供关键的有机丙氨酸酯中间体。最后，我们通过制备对映体天然产物证明了该反应的合成用途。最后，我们的初步结果(未优化)表明，由烯丙基-宝石-二硼酸酯与醛的烯丙化反应得到的1，2-氧硼杂环-3-烯可以通过铜催化的羧基化反应生成δ-内酯。

The goal of this grant proposal was to develop multi-component and/or multi-step coupling reactions with carbon dioxide as a key component to synthesize complex organic molecules. We demonstrated that 1,1-difluoroalkenes could undergo fluorocarboxylation reactions to furnish α-trifluoromethyl carboxylic acids in excellent yields. This synthetic protocol was superior to previous methods in that we were able to shorten the synthetic route to access these valuable molecules and avoided the use of expensive fluorinating reagents.Moreover, we developed a copper- and silver-catalyzed reductive carboxylation reaction of propargyl alcohols and amines to furnish γ-lactones and lactams in good yields. The key for this transformation was the use of Red-Al as a reducing agent can could undergo a distal trans-hydrometallation process to furnish the key organoalanate intermediate. Furthermore, we demonstrated the synthetic utility of this reaction by preparing an enantiopure natural product.Finally, we have preliminary results (unoptimized) that shows 1,2-oxaborinan-3-enes, derived from the allylation of allylic-gem-diboronate esters and aldehydes, can undergo copper-catalyzed carboxylation reactions to furnish δ-lactones.