Asymmetric Synthesis with Chiral Heteroalkyl Radicals

手性杂烷基自由基的不对称合成

• 批准号: 9616632
• 负责人: Philip Garner
• 金额: $ 34.55万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9616632&HistoricalAwards=false
• 关键词: Asymmetric; Synthesis; Chiral; Heteroalkyl; Radicals

The Organic Synthesis Program supports Professor Philip P. Garner, of the Department of Chemistry of Case Western Reserve University, in his studies of the development of a new class of recyclable chiral auxiliaries for asymmetric synthesis with chiral heteroalkyl radicals. Prototype hydroxyalkyl radical equivalents contain a chiral acetal group derived from either carbohydrates or terpenes. General methods, including radical translocation, for the formation of chiral acetaloxyalkyl radicals are under development for the preparation of these materials. Systematic variation of the auxiliary structure, coupled with ab initio transition state structure modeling, addresses the nature of the interactions responsible for asymmetric induction and facilitates their optimization. Both inter- and intramolecular variants of atom/group transfer reactions as well as additions to carbon-carbon double bonds are explored, as is methodology to permit the efficient removal and reuse of the chiral auxiliaries. Bidirectional and iterative versions of asymmetric `radical aldol` reactions promise stereocontrolled access to 1,3-polyols. In contrast to the often well-defined chemistry of compounds containing even numbers of electrons, compounds containing an unpaired electron (radicals) are often so reactive that their reaction chemistry is difficult to harness. Lack of reaction control is a particular problem in the attempted synthesis via radicals of compounds displaying the property of chirality, wherein a molecule differs from another in the same way a right hand differs from a left. With the support of the Organic Synthesis Program, Professor Philip P. Garner, of the Department of Chemistry of Case Western Reserve University, is developing chemical approaches which allow the exploitation of the intrinsic reactivity of radicals while maintaining a high level of control over the chirality of the resulting products. These approaches offer new routes for the synthesis of biologically active compounds, which are often chiral.

有机合成计划支持凯斯西储大学化学系的菲利普·P·加纳教授研究开发一类新型可回收手性助剂，用于手性杂烷基的不对称合成。原型羟基烷基当量物含有从碳水化合物或萜烯衍生的手性缩醛基团。手性乙酰氧基烷基形成的一般方法，包括自由基转移，正在开发中，以制备这些材料。辅助结构的系统变化与从头算过渡态结构建模相结合，解决了导致不对称诱导的相互作用的性质，并促进了它们的优化。探索了原子/基团转移反应的分子间和分子内变体以及碳-碳双键的加成，以及允许高效去除和重复使用手性辅助剂的方法。不对称自由基醛缩合反应的双向和迭代版本保证了对1，3-多元醇的立体控制访问。与含有偶数个电子的化合物通常定义明确的化学相反，含有不成对电子(自由基)的化合物往往非常活跃，以至于它们的反应化学很难驾驭。在通过显示手性性质的化合物的自由基进行合成的尝试中，缺乏反应控制是一个特别的问题，其中一个分子与另一个分子的不同方式与右手与左手的不同相同。在有机合成计划的支持下，凯斯西储大学化学系的菲利普·P·加纳教授正在开发化学方法，这种方法可以利用自由基的内在反应性，同时保持对结果产物的手性的高水平控制。这些方法为合成生物活性化合物提供了新的途径，这些化合物通常是手性的。