Novel Asymmetric Routes to 2-Oxetanones and Their Application

本项目将继续致力于开发通过有机催化不对称合成新型β-内酯（2-氧杂环丁酮）的简明方法。特别是，进一步发展的刘易斯碱促进，羟醛-内酯化（净环加成），同时构建一个C-C键和一个C-O键将追求获得这些通用的应变杂环。 除了新型路易斯碱启动子的研究外，还将进行机理研究以进一步了解整个反应途径，包括通过SN 2途径进行的潜在酰基取代。 此外，这些杂环的新的转化，包括环的扩张通过双环和三环β-内酯的异向重排的方式将进一步探索。 假设驱动的新的反应途径，包括烯醇化铵和延长和中断森田-贝利斯-希尔曼过程的研究将继续进行。 所开发的方法和工艺的实用性将通过应用于海绵内酯和姜黄内酯的全合成而突出。在教育目标方面，实验室研究转化为教学实验室将继续沿着多媒体方法的进一步发展，以传达有机合成的社会意义。有了这个奖项，有机和高分子化学计划是支持教授丹尼尔罗莫的化学系在得克萨斯州A M大学的研究。 Romo教授的研究工作围绕着β-内酯合成的催化，不对称方法的发展及其在合成中的应用，包括天然产物的全合成。 这项研究的结果将有助于进一步使用和应用这些未充分利用的杂环，这些杂环具有多种反应模式，使它们成为高度通用的有机合成中间体。 所提出的方法的成功开发将对制药和农业工业中的有机合成产生影响，因为正在开发的方法是稳健的和“用户友好的”。“此外，目标天然产物的合成将对进一步了解基本细胞过程产生更广泛的影响。

This project will continue work on the development of concise methods for the asymmetric synthesis of novel beta-lactones (2-oxetanones) via organocatalysis. In particular, further development of Lewis base-promoted, aldol-lactonizations (net cycloadditions) that construct a C-C bond and a C-O bond simultaneously will be pursued to access these versatile strained heterocycles. In addition to studies of novel Lewis-base promoters, mechanistic studies will be undertaken to gain further insights into the overall reaction pathway including a potential acyl substitution proceeding via an SN2 pathway. In addition, novel transformation of these heterocycles including ring expansions by way of dyotropic rearrangements of bicyclic and tricyclic beta-lactones will be explored further. Hypothesis driven studies of novel reaction pathways involving ammonium enolates and including extended and interrupted Morita-Baylis-Hillman processes will be pursued. The utility of the methods and processes developed will be highlighted by applications to the total synthesis of spongiolactone and curcumalactone. With respect to educational objectives, the translation of laboratory research into the teaching laboratory will continue along with further development of multimedia approaches for conveying the societal relevance of organic synthesis.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Daniel Romo of the Department of Chemistry at Texas A&M University. Professor Romo's research efforts revolve around the development of catalytic, asymmetric methods for the synthesis of beta-lactones and their application in synthesis including natural product total synthesis. The results of this research will contribute significantly to further use and application of these underutilized heterocycles, which possess a diverse array of reactivity modes making them highly versatile intermediates for organic synthesis. Successful development of the proposed methods will have an impact on organic synthesis in the pharmaceutical and agricultural industries as the methods being developed are robust and "user friendly." In addition, synthesis of the targeted natural products will have broader impacts in enabling the further understanding of fundamental cellular processes.