Stereoselective Radical Reactions for Amine Synthesis

胺合成的立体选择性自由基反应

• 批准号: 0096803
• 负责人: Gregory Friestad
• 金额: $ 33.52万
• 依托单位: University of Vermont & State Agricultural College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0096803&HistoricalAwards=false
• 关键词: Stereoselective; Radical; Reactions; Amine; Synthesis

The proposed research addresses the direct asymmetric synthesis of amines. Rather than relying on indirect routes such as carbonyl addition or oxidative alkene functionalization to form chiral alpha-branched amines, stereocontrolled free radical addition reactions will be used, creating a new stereocenter and a new carbon-carbon bond in a single operation from achiral precursors. Within this context are addressed three specific aims - internal diastereocontrol by preexisting stereochemistry using temporary tethers in radical cyclization, external stereocontrol in intermolecular radical addition using nitrogen-linked removable and reusable chiral auxiliaries, and catalyst stereocontrol with Lewis acids bearing chiral ligands.Nitrogen-containing groups ("amines") with precisely defined three-dimensional structure (stereochemistry) are found in many biologically active molecules and designed pharmaceuticals. Experimental methods for the direct synthesis of such compounds with the necessary stereochemical control are uncommon. With the support of the Organic Synthesis Program, Professor Gregory K. Friestad, of the Department of Chemistry at the University of Vermont and State Agricultural College, is studying new methods for the synthesis of amines. Professor Friestad explores the introduction of stereochemistry in reactions of free radicals (molecular groupings containing an unpaired electron) through a variety of approaches, including the temporary linking of reactants. These studies are leading to an enhanced understanding of the reaction chemistry of free radicals and to new and efficient methods for the synthesis of biologically active amines.

该研究涉及胺的直接不对称合成。不是依赖于间接途径如羰基加成或氧化烯烃官能化以形成手性α-支链胺，而是将使用立体控制的自由基加成反应，在单个操作中由非手性前体产生新的立构中心和新的碳-碳键。在此背景下，提出了三个具体目标-通过在自由基环化中使用临时系链的预先存在的立体化学进行内部非对映体控制，在分子间自由基加成中使用氮连接的可去除和可重复使用的手性助剂进行外部立体控制，和用带有手性配体的刘易斯酸进行催化剂立体控制。具有精确定义的三维结构（立体化学）的多胺（“胺”）存在于许多生物活性分子和设计的药物中。在必要的立体化学控制下直接合成这类化合物的实验方法并不常见。在有机合成项目的支持下，Gregory K.弗蒙特大学和州立农业学院化学系的弗里斯塔正在研究合成胺的新方法。Friestad教授通过各种方法，包括反应物的临时连接，探索了在自由基（含有未配对电子的分子组）反应中引入立体化学。这些研究正在导致对自由基的反应化学的增强理解，以及用于合成生物活性胺的新的和有效的方法。