New Catalyst Scaffolds for Asymmetric Addition to Imines

用于亚胺不对称加成的新型催化剂支架

• 批准号: 7104306
• 负责人: EMILY A PETERSON
• 金额: $ 4.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-18 至 2007-07-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104306
• 关键词: Schiff bases; carbon; catalyst; chemical addition; chemical bond; chemical reaction; chemical structure function; chemical synthesis; ferrocene; imines; ligands; monoterpenes; postdoctoral investigator; quinoline; stereoisomer

DESCRIPTION (provided by applicant): Addition of carbon nucleophiles to imines is one of the most widely utilized C-C bond forming reactions in organic chemistry and thus development of asymmetric versions of this reaction is an important endeavor. Recently, progress toward this goal has been achieved with N-aryl imines. Unfortunately, the existing catalytic systems do not provide high ee's with N-aryl imines, except those derived from 2-hydroxyaniline. A new catalyst system needs to be developed that can catalyze the asymmetric addition of nucleophiles to a wide array of N-aryl imines. This important class of substrates can act as precursors to an array of natural products and drug targets containing aniline-bearing stereogenic centers. This proposal outlines the design of two new chiral Lewis acid frameworks developed to catalyze the enantioselective addition to N-aryl imines. The proposed catalysts arise from modification of Jacobsen's chiral (salen)AI(lll) Strecker catalyst. The first proposed catalyst incorporates planar chiral ferrocenyl ligands into a Schiff base framework. The second proposed catalyst structure is derived from alpha-pinene and combines two molecules of pinene into a unique C2-symmetric ligand scaffold. Targeted transformations are the Strecker and Mannich reactions as well as the aza-Diels-Alder reaction to form enantioenriched tetrahydroquinolines.

描述（由申请人提供）： 碳亲核试剂加成亚胺是有机化学中最广泛使用的C-C键形成反应之一，因此开发该反应的不对称版本是一项重要的奋进。最近，N-芳基亚胺已经实现了这一目标的进展。不幸的是，现有的催化体系不提供高ee的N-芳基亚胺，除了那些衍生自2-羟基苯胺。需要开发一种新的催化剂体系，可以催化亲核试剂对各种N-芳基亚胺的不对称加成。这类重要的底物可以作为一系列天然产物和含有苯胺的立体中心的药物靶点的前体。 该方案设计了两种新的手性刘易斯酸骨架催化N-芳基亚胺的对映选择性加成反应。所提出的催化剂由Jacobsen的手性（salen）Al（III）Strecker催化剂的改性产生。第一个提出的催化剂将平面手性二茂铁基配体纳入席夫碱框架。第二种提出的催化剂结构衍生自α-蒎烯，并将两个分子的蒎烯组合成独特的C2-对称配体骨架。靶向转化是Strecker和Mannich反应以及氮杂-Diels-桤木反应，以形成对映体富集的四氢喹啉。