NEW STRATEGIES IN TOTAL SYNTHESIS

结构和立体化学的复杂性在许多 具有重要生物医学意义的天然产物呈现出令人敬畏的 对合成有机化学家的挑战。我们的研究计划 重点发展新的概念和战略，以 有机合成。通常，为了执行这样的策略，新的 反应必须从理论上和/或机械上推导出来 考虑因素。在这种新反应的发展过程中， 重点是选择性。具有重要生物学意义的天然 产品用作说明这些新功能的模板 策略、概念和反应。 合成任何有机分子的核心是能够 形成碳-碳键。总的来说，最常见的 碳-碳骨形成的方法包括 使用碳离子。尽管如此，其他的结合方式 队形往往是可取的。因此，虽然我们的研究 该计划包括几个不同的领域，潜在的主题 非碳离子碳-碳键的形成 强调。 研究职业发展建议书部分概述了 两个主要独立研究领域的项目。第一 一节描述了综合和机械的研究 一系列新型取代基受控Claisen的研究进展 重新安排。除了允许方便和 对各种复杂系统的立体控制访问， 拟议的重新安排将提供对 克莱森过渡态的基本性质。第二 部分描述了我们对替代方案的持续开发 通过环加剂形成“羟醛加合物”的策略 路线。该方法的核心是潜在的合成等价性 将三角洲2-异恶唑啉转化为β-羟基酮。各种各样的 立体控制异恶唑啉形成的新方法是 建议，并计划应用于全合成。它 预计这一环加成策略将提供 第一个有效和通用的替代羟醛类反应的方法。 最后，第三个主要研究方向，开发和使用 有机合成中的新的自由基反应不包括在 建议书部分。为此，随行的四人 论文集中在这一领域，以说明 这项计划的进展非常出色。

The structural and stereochemical complexities embodied in many biomedically important natural products present a formidable challenge to synthetic organic chemists. Our research program focuses on the development of new concepts and strategies for organic synthesis. Frequently, to execute such strategies, new reactions must be derived via theoretical and/or mechanistic considerations. In the development of such new reactions, the emphasis is on selectivity. Biologically important natural products are used as templates with which to illustrate these new strategies, concepts, and reactions. Central to the synthesis of any organic molecule is the ability to form carbon-carbon bonds. In general terms, the most common methods for carbon-carbon bone formation involve the employment of carbonions. Nonetheless, other methods of bond formation are frequently desirable. Thus, while our research program encompasses several diverse areas, the underlying theme of non-carbanionic carbon-carbon bond formation has been emphasized. The Research Career Development proposal section outlines projects in two major independent research areas. The first section describes the investigation of synthetic and mechanistic aspects of a series of novel substituent-controlled Claisen rearrangements. In addition to permitting facile and stereocontrolled access to a variety of complex systems, the proposed rearrangements will provide unique insights into the fundamental nature of Claisen transition states. The second section describes our continued development of an alternative strategy for the formation of "aldol adducts" via a cycloadditive route. Central to the approach is the latent synthetic equivalence of a Delta 2-isoxazoline to a beta-hydroxy ketone. A variety of new methods for stereocontrolled isoxazoline formation are proposed, and applications for total synthesis are also planned. It is anticipated that this cycloadditive strategy will provide the first powerful and general alternative to the aldol-type reaction. Finally, a third major research thrust, the development and use of novel free radical reactions in organic synthesis is not included in the proposal section. For this reason, the four accompanying papers are concentrated in this single area to illustrate the excellent progress of this program.