Enantioselective Catalysis with Cyclopropenimines

描述（由申请人提供）：获取对映体富集分子对现代生物医学研究至关重要。有机合成中许多最重要的反应都依赖于质子转移作为关键的机理步骤。因此，手性Bronsted碱催化已成为一种有前途的策略，用于生产有价值的对映体富集形式的分子构建块。然而，由于现有催化剂平台的碱度相对有限，这一催化领域一直受到阻碍，这大大限制了这些方法的广泛应用。因此，有一个明显的动力，以提高效力和有效性的新催化剂的发明，这可能为对映选择性Bronsted碱催化的挑战提供一个通用的解决方案。为此，我们开发了一种全新的高活性和对映选择性手性Bronsted碱催化剂，基于2,3-双（二烷基胺）环丙烯胺。值得注意的是，环丙烯胺的碱度明显高于现有的催化平台。基于我们早期的演示，我们设想环丙烯胺可能成为对映选择性Bronsted碱催化的最终平台。环丙烯胺具有独特的优点：(1)高碱性和高反应性；（二）易于准备；(3)与水、好氧条件的相容性；(4)催化剂模块化；(5)可扩展性。在每个目标项目中

DESCRIPTION (provided by applicant): Access to enantioenriched molecules is crucial to modern biomedical research. Many of the most important reactions in organic synthesis rely on proton transfer as a key mechanistic step. As such, chiral Bronsted base catalysis has emerged as a promising strategy for the production of valuable molecular building blocks in enantioenriched form. This area of catalysis has been impeded, however, by the relatively limited basicity of established catalyst platforms, which has significantly curtailed the widespread application of these approaches. Thus, there exists a clear impetus for the invention of new catalysts with increased potency and effectiveness, which could provide a general solution to the challenge of enantioselective Bronsted base catalysis. Toward this end, we have developed a fundamentally new class of highly reactive and enantioselective chiral Bronsted base catalyst, based on 2,3-bis(dialkylamino)cyclopropenimines. Notably, cyclopropenimines possess significantly higher basicity than established catalytic platforms. Based on our early demonstrations, we envision that cyclopropenimines may emerge as the definitive platform for enantioselective Bronsted base catalysis. Cyclopropenimines offer unique advantages of: (1) high basicity and reactivity; (2) ease of preparation; (3) compatibility with aqueous and aerobic conditions; (4) catalyst modularity; and (5) amenability to scale. In each of the projects targeted herein, we aim to apply cyclopropenimine catalysis to address a prominent challenge in organic synthesis. The asymmetric transformations targeted in this grant are either currently unknown or suffer from significant limitations of substrate scope. Among the specific reactions that we aim to develop in the context of this grant are: enantioselective glycine Mannich and ?-thio Mannich reactions; ?-arylations with quinones and benzene oxides; Michael additions with low acidity nucleophiles, including diazoesters; allylic alkylations; and enantioselective conjugate additions of phenols, amines, and nitrogen heterocycles. The development of these proposed transformations and the further establishment of the new cyclopropenimine catalyst platform will represent significant advances for the field of organic synthesis.