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

前言：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生产农用化学品、药物和聚合物。这些中间体通常被称为“积木”，因为它们可以被看作是“分子砖”，当它们组合在一起时，就会融入药物、天然产物和聚合物的主体结构中。理想的构筑基块应1)易于获得；2)可用于新的成键反应；3)至少具有一个杂原子；4)使用简单的反应条件容易地转化为更高级的中间体；以及5)以对映体形式可用。乙烯基环氧化合物和乙烯基氮杂环丙烷具有这样的性质，因此它们是有机和聚合物化学中广泛使用的合成中间体，它们也偶尔出现在天然产品中，特别是在聚酮类化合物中。此外，目前的方法存在合成步骤多、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等局限性。我们的研究计划旨在开发一种技术来解决这些缺点，从而通过高度收敛的方法极大地扩大可获得的乙烯基环氧化合物/氮杂环丁烷的范围。目标(O1-4)：我们的目标是通过最非传统的断开：环氧化物和烯烃之间的连接，开发一种环氧乙烯基环氧化物和氮杂环丙烷的统一合成方法。我们将研究它的范围，并将其应用于修改结构的聚酮类天然产物机械的全合成。研究方法和途径：(1)开发一种统一的环氧乙烯基醚和乙烯基氮杂环丙烷的合成方法。(O2)底物范围的评估：烷基、苯乙烯和三氟甲基环氧化物/氮杂环丙烷。(03)由三氟甲基乙烯基环氧化物合成高级中间体。(O4)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.