New organosulfur-based strategies for efficient and selective organic synthesis

基于有机硫的高效、选择性有机合成新策略

基本信息

批准号：
9803331
负责人：
Oleg V Larionov
金额：
$ 28.3万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-05 至 2023-06-30
项目状态：
已结题

项目摘要

Organosulfur compounds have a major role in advancing human health and well-being. A quarter of the most prescribed drugs contain sulfur, and sulfur is the most common heteroatom in all approved drugs after oxygen and nitrogen. The sulfur-containing functional groups also enable a variety of reactions that are used to synthesize natural products, biological probes, therapeutic agents, dyes, and advanced functional materials. However, the diverse and pluripotent reactivities of organosulfur compounds lead to low chemo-, regio- and stereoselectivities that adversely affect development of stereo- and regioselective approaches in organic synthesis. The long-term goal of this research is to advance the field of organic synthesis by streamlining synthetic access to centrally important organosulfur compounds and systematically developing their regio- and stereoselective transformations to broad classes of valuable functionalities and structural motifs. The intermediate oxidation state organosulfur reagents sulfinates have the potential to solve limitations of current methods of synthesis of organosulfur compounds and to enable new regio- and stereoselective reactions to a wide range of functionalized small molecules. However, there is a lack of efficient methods of synthesis of sulfinates directly from abundant precursors and a gap in fundamental understanding of the nearly entirely unexplored reactivity of sulfinates in the context of stereoselective C‒C bond forming cross-coupling reactions The overall objective of this research is to develop methods of synthesis of sulfinates from abundant precursors and to develop regio- and stereoselective C−C bond forming reactions of sulfinates. This objective will be accomplished by systematically developing three research topics encompassing currently elusive synthetic methods. In the first part, stereodivergent catalytic cross-coupling reactions of intermediate sulfinates will be developed into a broad synthetic platform to access conjugated dienes and polyenes with high and predictable regio-and stereoselectivity. In the second part, a generic platform for harnessing abundant C−H bonds by means of a regioselective C−H sulfination will be developed. The third part is focused on catalytic alkene sulfination reactions to draw from abundance and reactivity of alkenes. Upon completion of this research program, a broad range of currently synthetically challenging functionalized molecules including sulfur-containing ones will become readily accessible for organic synthesis and drug discovery applications, contributing to improvement of human healthcare through more efficient syntheses of small molecule biological probes and therapeutic agents.

有机硫化合物在促进人类健康和福祉方面发挥着重要作用，其中四分之一是有机硫化合物。处方中含有硫的药物，硫是所有批准药物中继氧之后最常见的杂原子含硫官能团还可以进行多种反应。合成天然产物、生物探针、治疗剂、染料和先进功能材料。然而，有机硫化合物的多样化和多能反应性导致低化学、区域和立体选择性对有机领域立体选择性和区域选择性方法的发展产生不利影响这项研究的长期目标是通过简化有机合成领域。合成获得重要的有机硫化合物并系统地开发其区域和立体选择性转化为广泛的有价值的功能和结构主题。中间氧化态有机硫试剂亚磺酸盐有可能解决目前的局限性有机硫化合物的合成方法以及使新的区域和立体选择性反应成为可能然而，目前缺乏有效的合成方法。亚磺酸盐直接来自丰富的前体，并且对几乎完全的基本理解存在差距亚磺酸盐在立体选择性 C-C 键形成交叉偶联反应中的未探索反应性本研究的总体目标是开发从丰富的前体合成亚磺酸盐的方法并开发亚磺酸盐的区域和立体选择性 C−C 键形成反应。通过系统地开发三个研究主题来完成，这些主题涵盖目前难以捉摸的合成在第一部分中，将进行中间体亚磺酸盐的立体发散催化交叉偶联反应。发展成为一个广泛的合成平台，以获取具有高且可预测的共轭二烯和多烯第二部分是利用丰富的 C−H 键的通用平台。将开发区域选择性 C−H 亚磺化的方法。第三部分重点关注催化烯烃亚磺化。该研究计划完成后，从烯烃的丰度和反应性中得出了广泛的反应。目前合成上具有挑战性的一系列功能化分子，包括含硫分子，将易于有机合成和药物发现应用，有助于改进通过更有效地合成小分子生物探针和疗法来改善人类医疗保健代理。