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首页> 外文学位 >Enantioselective synthesis and reactivity of bicyclobutanes: Strained molecular platforms for 4-, 5-, and 6-membered ring synthesis and rhodium(II)-catalyzed reactions of diazoesters with organozinc reagents.
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Enantioselective synthesis and reactivity of bicyclobutanes: Strained molecular platforms for 4-, 5-, and 6-membered ring synthesis and rhodium(II)-catalyzed reactions of diazoesters with organozinc reagents.

机译：双环丁烷的对映选择性合成和反应性：重氮化合物与有机锌试剂的4元，5元和6元环合成和铑（II）催化反应的应变分子平台。

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摘要

This dissertation is centered on reaction methodology and its application in the total synthesis of natural products. The results described herein include the development of a new method for enantioselective synthesis of cyclobutanes, the total synthesis of cyclobutane-containing natural products, the development of the first examples of transition-metal catalyzed vinylcyclobutane ring expansion reactions, and the rhodium-catalyzed organozincation of diazoesters.;The rich chemistry of diazocompounds rapidly builds complexity across many modes of reactivity. The propensity of Rh(II)-carbenes to undergo beta-hydride migration has been a long standing limitation to this chemistry. In Chapter 1, I will provide an overview of chemistries involving alpha-alkyl-beta-diazoesters that contain beta-hydrogens including the major contributions from our group. The ability to limit this undesired pathway by studying temperature and ligand effects has further extended the powerful chemistry of diazocompounds.;Rhodium(II)-catalyzed intermolecular cyclopropanation of diazoesters and alkenes has been widely studied and applied to complex synthesis; however, reports of intramolecular cyclopropanation had been quite limited. In Chapter 2, I will discuss the development of general conditions for the enantioselective intramolecular cyclopropanation or bicyclobutanation of alpha-diazoesters. Additionally, this chemistry has been coupled with a Cu(I)-catalyzed homoconjugate addition of Grignard reagents to bicyclobutanes in a one-pot procedure to provide rapid access to complex cyclobutanes in a highly stereocontrolled manner.;Cyclobutane-containing natural products exhibit diverse biological activity and have shown promise as therapeutic leads in areas including oncology, neurology, pain management, infectious diseases, and respiratory diseases. General and stereoselective methods to access unsymmetrical cyclobutane cores are still needed. In Chapter 3, I describe the application of the Rh(II)-catalyzed bicyclobutanation/Cu(I)-catalyzed homoconjugate addition of diazoesters for the synthesis of cyclobutane-containing natural products. I have completed the total synthesis of piperarborenine B in 0.4 g, 10 steps, and 8% overall yield in 1 week. I have also applied this methodology towards the synthesis of incarvillateine D and SB-FI-26 both of which have shown promise in pain management via adenosine receptor pathways.;In contrast to the well-known and widely-utilized vinylcyclopropane--cyclopentene rearrangement, the analogous vinylcyclobutane--cyclohexene rearrangement has found limited use due to the requirement of harsh conditions. In Chapter 4, I will discuss the development of the first examples of transition metal catalyzed ring expansions of vinylcyclobutanes. I have discovered the combination of Ni(0) and NHC ligands provides cyclohexenes while Rh(I)-catalysts provide exclusively cyclopentenes.;Organozinc reagents are widely used reagents in light of their excellent functional group tolerance; however, their use in Rh(II)-catalyzed reactions with diazoesters has not been reported. In Chapter 5, I describe the development of general conditions for the Rh(II)-catalyzed organozincation of diazoesters. The resulting hydrazone products have been elaborated to tertiary aminoesters and pyrazoles.
机译：本文的重点是反应方法及其在天然产物的全合成中的应用。本文所述的结果包括开发一种新的对映选择性合成环丁烷的方法，全合成含环丁烷的天然产物，开发第一个过渡金属催化的乙烯基环丁烷环膨胀反应的实例以及铑催化的环丁烷的有机锌化。重氮化合物的丰富化学成分迅速在多种反应模式之间建立了复杂性。 Rh（II）-卡宾经历β-氢化物迁移的倾向一直是该化学的长期局限性。在第一章中，我将概述涉及包含β-氢的α-烷基-β-重氮酯的化学反应，包括我们小组的主要贡献。通过研究温度和配体效应来限制这种不希望有的途径的能力进一步扩展了重氮化合物的强大化学作用。铑（II）催化的重氮酯和烯烃的分子间环丙烷化已得到广泛研究，并用于复杂的合成中；然而，关于分子内环丙烷化的报道非常有限。在第二章中，我将讨论α-重氮酸酯的对映选择性分子内环丙烷化或双环丁酸酯化的一般条件的发展。此外，这种化学方法还通过一锅法将Cuignard试剂的Cu（I）催化均轭加成到双环丁烷中，从而以高度立体可控的方式快速进入复杂的环丁烷中;含环丁烷的天然产物表现出多种生物学特性并在肿瘤学，神经病学，疼痛治疗，传染病和呼吸道疾病等领域具有治疗潜力。仍需要访问不对称环丁烷核的通用和立体选择方法。在第3章中，我描述了重氮酸酯的Rh（II）催化的双环丁烷/ Cu（I）催化的均聚物加成在合成含环丁烷的天然产物中的应用。我在1周内完成了0.4 g，10步和8％总产率的胡椒基硼烯B的总合成。我也将这种方法应用于合成carcarvillateine D和SB-FI-26，这两种化合物均显示出通过腺苷受体途径进行疼痛控制的前景;与众所周知且广泛使用的乙烯基环丙烷-环戊烯重排相比，由于苛刻条件的要求，类似的乙烯基环丁烷-环己烯重排的用途受到限制。在第四章中，我将讨论乙烯基环丁烷在过渡金属催化的环膨胀中的第一个实例的开发。我发现Ni（0）和NHC配体的组合提供了环己烯，而Rh（I）催化剂仅提供了环戊烯。；有机锌试剂因其出色的官能团耐受性而被广泛使用；但是，尚未报道它们在Rh（II）催化的重氮酯反应中的用途。在第5章中，我描述了Rh（II）催化的重氮酯有机锌合成一般条件的发展。生成的产物已被精制为叔氨基酯和吡唑。

著录项

  • 作者

    Panish, Robert A.;

  • 作者单位

    University of Delaware.;

  • 授予单位 University of Delaware.;
  • 学科 Organic chemistry.;Chemistry.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 429 p.
  • 总页数 429
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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