Stable Carbenes: Emerging Ligands for Catalysis

稳定的卡宾：新兴的催化配体

基本信息

批准号：
7479331
负责人：
GUY BERTRAND
金额：
$ 19.72万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7479331
关键词：
1,3-Butadiene 3-hydroxybutanal Academia Acidity Address Adopted Aldehydes Alkenes Amines Anions Area Attention BINAP Behavior Berlin Binding Biological Boron Carbon Catalysis Chemistry Chloride Ion Chlorides Class Collaborations Communities Complex Condition Coupling Development Electronics Electrons Environment Esters Exhibits Family Goals Hydrogenation Imines Indoles Industry Letters Ligands Metals Methanol Modification Molecular Conformation Nature Nitrogen PRTN3 gene Palladium Phosphines Phosphorus Physical condensation Positioning Attribute Preparation Process Property Purpose Range Reaction Reporting Research Rest Rhodium Role playing therapy Route Ruthenium Series Skeleton System Technology Testing Therapeutic Time Transition Elements amino group base carbanion carbene carbonyl compound carbonyl group catalyst cinnamic acid concept design driving force electron density experience indole interest novel phosphine programs success trend ylide

项目摘要

DESCRIPTION (provided by applicant): Efficient and selective preparation of organic molecules is critical for the synthesis of therapeutics. Many of the most proficient known processes depend on the availability of catalysts. One of the advantages of organometallic catalysis is the ability to tune the activity and selectivity through modification of the ligands around the metal center. Recently, major advances in catalysis, especially in Pd-cross-coupling reactions, have been reported thanks to the use of bulky, electron-rich phosphines and cyclic diaminocarbenes (NHCs). The proposed research program, built on our long standing experience in stable carbene synthesis, has as its objective the synthesis of cyclic carbenes that push upward the electronic and/or steric parameter scales characterizing both phosphine and NHC ligands, with special attention on families of ligands for which it will be possible to precisely tune the stereo-electronic parameters. There is a demanding need for technology to produce therapeutics in a pure enantiomeric form. For the asymmetric versions of the ligands, carbenes with a chirality center in a position alpha to the carbene, and bidentate ligands featuring C2 chirality and two very different donors will be prepared; this should result in high chiral induction effects. We will focus on palladium-catalyzed coupling reactions of aryl chlorides (Suzuki-Miyaura and Negishi processes) and on the alpha-arylation of aldehydes/imines. Thanks to this virtually unknown reaction, and because of the prominent role played by indoles in biological systems, we will develop a novel one-pot synthesis of a variety of indoles from imines and ortho-dihaloarenes. To accelerate the widespread implementation of our ligands, we have already formalized two collaborations and we are looking forward to further partnerships. The ultimate goal of this proposed research effort is to provide the catalytic community with new, readily available ligands, which will allow for the development of practical catalysts that will find applications in both industry and academia for the selective synthesis of biologically important compounds.

描述（由申请人提供）：有机分子的有效和选择性制备对于综合治疗剂至关重要。许多最熟练的已知过程取决于催化剂的可用性。有机金属催化的优点之一是能够通过修改金属中心周围的配体来调整活性和选择性。最近，由于使用了笨重的，富含电子的磷和环状二氨基碳苯（NHC），催化作用的重大进展，尤其是在PD-Cross耦合反应中。拟议的研究计划基于我们在稳定的碳合成中长期存在的经验，它的目标是环状碳烯的合成，这些碳烯的合成向上推动了电子和/或空间参数尺度，表征了磷酸和NHC配体，并特别关注该配体的家族，可以预见到它可以预见的是刻板的参数。需要技术以一种纯净的对映体形式生产治疗剂。对于配体的不对称版本，带有手性中心的卡宾斯（Carbenes）位于卡宾（Carbene）的位置，而双齿配体具有C2手性和两个截然不同的供体；这应该导致高性诱导效应。我们将重点关注芳基氯化物（铃木 - 米龙和尼古质过程）的钯催化偶联反应以及醛/丙醛的α-酰化。得益于这种几乎未知的反应，并且由于吲哚在生物系统中所起的重要作用，我们将开发出一种新型的单锅合成，以构成来自亚胺和邻苯甲烯烯的各种吲哚。为了加速我们的配体的广泛实施，我们已经正式化了两项合作，我们期待着进一步的合作伙伴关系。这项拟议的研究工作的最终目标是为催化社区提供新的，随时可用的配体，这将允许开发实用的催化剂，这些催化剂将在工业和学术界都在选择性合成生物学上重要的化合物中的应用。