Lithiation-borylation reactions and their application to the synthesis of vinyl epoxides

简介：有机化学的主要研究领域之一是开发合成有价值的中间体的新方法，这些中间体可广泛用于农药、药品和聚合物的制造。这些中间体通常被称为“构建块”，因为它们可以被视为“分子砖”，当它们组合在一起时，就被纳入药物、天然产物和聚合物的主要结构中。理想的构建模块应该1)易于访问；2)可用于新键形成反应；3)具有至少一个杂原子；4)在简单的反应条件下容易转化为更高级的中间体；5)以对映不纯形式存在。乙烯基环氧化物和乙烯基叠氮醚具有这些特性，因此它们是有机和聚合物化学中广泛使用的合成中间体，偶尔也会在天然产物中遇到，特别是在聚酮类化合物中。技术现状：尽管它们具有合成价值，但没有统一的方法可以从容易获得的起始材料合成乙烯基环氧化物和乙烯基叠氮醚。此外，目前的方法还存在一些局限性，如多步骤合成、条件苛刻、官能团耐受性差、区域选择性问题以及使用高活性中间体。我们的研究计划旨在开发一种解决这些缺点的技术，从而通过高度收敛的方法大大扩大可获得环氧乙烯/叠氮醚的范围。目标（O1-4）：我们的目标是通过最非常规的分离：环氧化物和烯烃之间的分离，开发乙烯基环氧化物和叠氮醚的统一合成。我们将研究其范围，并将其应用于聚酮天然产物machillene的修正结构的全合成。研究方法和途径：(1)建立乙烯基环氧化物和乙烯基叠氮醚的统一合成方法。（O2）评估底物范围：烷基、苯乙烯基和三氟甲基环氧化物/叠氮醚。(3)由三氟甲基环氧乙烯合成高级中间体。(4)机械烯的全合成。

Introduction: One of the main areas of research in Organic Chemistry is the development of new methodologies for the synthesis of valuable intermediates that can be widely used for the creation of agrochemicals, pharmaceuticals and polymers. These intermediates are often referred to as “building blocks”, because they can be seen as “molecular bricks”, which, when put together, are incorporated into the main structure of drugs, natural products and polymers. The ideal building block should 1) be easy to access; 2) be utilizable in new bond forming reactions; 3) have at least one heteroatom; 4) be readily transformed into more advanced intermediates using simple reaction conditions; and 5) be available in enantiopure form. Vinyl epoxides and vinyl aziridines possess such attributes, thus they are widely used synthetic intermediates in organic and polymer chemistry and they are also occasionally encountered in natural products, particularly within the polyketide family.State of the Art: Despite their synthetic value, there is no unified method for the synthesis of both vinyl epoxides and vinyl aziridines from readily accessible starting materials. Moreover, current methods suffer from limitations such as multistep synthesis, harsh conditions, poor functional group tolerance, regioselectivity issues, and the use of highly reactive intermediates. Our research program aims to develop a technology that addresses these shortcomings, thereby greatly expanding the range of accessible vinyl epoxides/aziridines through a highly convergent approach.Objectives (O1-4): We aim to develop a unified synthesis of vinyl epoxides and aziridines through the most unconventional disconnection: between the epoxide and the alkene. We will investigate its scope and apply it to the total synthesis of a revised structure of the polyketide natural product machillene.Research Methodology and Approach: (O1) To develop a unified method for the synthesis of vinyl epoxides and vinyl aziridines. (O2) Assessment of the substrate scope: alkyl, styrenyl and trifluoromethyl epoxides/aziridines.(O3) Synthesis of advanced intermediates from trifluoromethyl vinyl epoxides. (O4) Total synthesis of machillene.