Asymmetric Nucleophilic Catalysis

描述(申请人提供)：该计划将探索4-(二甲氨基)吡啶的平面手性衍生物(DMAP)和手性膦催化的对映选择性过程的发展。研究将主要集中在它们作为亲核催化剂的应用；此外，最近发现的DMAP衍生物的化学维度，它们作为Bronsted酸催化剂的用途(质子化形式)也将继续进行。将研究一系列不同的反应(例如，β-内酰胺的Staudinger合成、醇和胺的动力学拆分、环化和卤化)。实现这一计划的目标将有助于获得高度对映体富集型的重要化合物家族。相关性：由于生命分子(蛋白质、DNA、RNA、糖等)的“左旋性”，特定化合物的两个镜像版本(“对映体”)通常表现出相当不同的生物活性。因此，极有必要有选择地只产生两种镜像化合物中的一种(排名前十的药物中有九种具有“手性”活性成分，其中七种是单手性的(对映体))。对映选择性催化是本研究计划的重点，是实现这一目标的一种特别有吸引力的策略。

DESCRIPTION (provided by applicant): This program will explore the development of enantioselective processes catalyzed by planar-chiral derivatives of 4-(dimethylamino)pyridine (DMAP) and by chiral phosphines. The investigation will focus primarily on their application as nucleophilic catalysts; in addition, a recently discovered dimension of the chemistry of the DMAP derivatives, their use (in protonated form) as Bronsted acid catalysts, will be pursued. A diverse array of reactions (e.g., Staudinger synthesis of beta-lactams, kinetic resolutions of alcohols and amines, annulations, and halogenations) will be examined. Achieving the objectives of this program will facilitate access to important families of compounds in highly enantioenriched form. Relevance: Due to the "handedness" of the molecules of life (proteins, DNA, RNA, sugars, etc.), the two mirror- image versions ("enantiomers") of a particular compound often display quite different biological activity. As a result, there is a tremendous need to selectively generate just one of the two mirror-image compounds (nine of the Top 10 pharmaceutical drugs have "handed" active ingredients, seven of which are single-handed (enantiopure)). Enantioselective catalysis, the focus of this research program, is a particularly attractive strategy for achieving this objective.