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

简介：有机化学研究的主要领域之一是开发合成有价值中间体的新方法，这些中间体可广泛用于制造农用化学品，药物和聚合物。这些中间体通常被称为“积木”，因为它们可以被视为“分子砖”，当它们放在一起时，它们被纳入药物，天然产物和聚合物的主要结构中。理想的结构单元应该1）容易获得; 2）可用于新的键形成反应; 3）具有至少一个杂原子; 4）使用简单的反应条件容易地转化为更高级的中间体;和5）以对映体纯的形式获得。乙烯基环氧化物和乙烯基氮杂环丙烷具有这样的属性，因此它们是有机和聚合物化学中广泛使用的合成中间体，并且它们也偶尔在天然产物中遇到，特别是在聚酮化合物家族中。此外，目前的方法受到诸如多步合成、苛刻条件、差的官能团耐受性、区域选择性问题和使用高反应性中间体的限制。我们的研究计划旨在开发一种技术，解决这些缺点，从而大大扩大了可访问的乙烯基环氧化物/氮杂环丙烷的范围，通过一个高度收敛的approach.Objectives（O 1 -4）：我们的目标是开发一个统一的合成乙烯基环氧化物和氮杂环丙烷通过最非常规的断开：之间的环氧化物和烯烃。我们将研究它的范围，并将其应用到全合成的聚酮化合物天然产物machillene.Research方法和途径的修订结构：（O 1）开发一个统一的方法合成乙烯基环氧化合物和乙烯基氮杂环丙烷。(O2)评估底物范围：烷基、苯乙烯基和三氟甲基环氧化物/氮丙啶。(O3)由三氟甲基乙烯基环氧化物合成高级中间体。(O4)Machillene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.