NEW STRATEGIES IN TOTAL SYNTHESIS

结构和立体化学的复杂性体现在许多 生物医学上重要的天然产品提出了一个强大的 对有机合成化学家的挑战 我们的研究项目 重点是发展新的概念和战略， 有机合成 通常，为了执行这些战略， 反应必须通过理论和/或机理推导出， 注意事项。 在开发这种新反应的过程中， 重点是选择性。 具有生物重要性的天然 产品被用作模板来说明这些新的 策略、概念和反应。 任何有机分子合成的核心是 形成碳碳键。 一般来说，最常见的 碳-碳骨形成的方法包括 碳离子的使用。 尽管如此，其他债券的方法 经常需要形成。 因此，虽然我们的研究 该计划包括几个不同的领域，基本主题 非碳负离子碳-碳键的形成 重点介绍 研究职业发展建议部分概述了 两个独立研究领域的项目。 第一 第一节描述了合成和机理的调查 一系列新的取代基控制的Claisen 重新安排 除了允许轻松和 立体控制访问各种复杂的系统， 拟议的重新安排将提供独特的见解 克莱森过渡态的基本性质。 第二 一节描述了我们对替代产品的持续开发 通过环状添加剂形成“羟醛加合物”的策略 路线 该方法的核心是潜在的综合等值 将δ 2-异恶唑啉转化为β-羟基酮。 各种 用于立体控制的异恶唑啉形成的新方法是 建议，并计划应用于全合成。 它 预计这种环加成策略将提供 第一个强大的和一般的替代羟醛型反应。 最后，第三个主要的研究重点，开发和使用 有机合成中的新自由基反应不包括在 提案部分。 为此，四位随行 论文集中在这一单一领域，以说明 这个项目的出色进展。

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.