Efficient, catalytic, asymmetric crossed acyloin condensations

在安息香缩合（BC）被发现178年后，用于两个不同醛分子的交叉偶联以产生对映体富集的α-羟基酮产物的一般小分子催化体系仍然是我们所不能及的。我们打算发起一个系统的研究计划，旨在解决（在我们看来）阻碍偶姻进展的几个挑战。苯偶姻化学在过去的两个世纪。初步的数据和模型的分析强烈表明，一种新的双功能的手性有机催化剂系统在我们的小组开发将能够促进各种不对称的交叉苯偶姻缩合（ACBC反应），其他系统似乎已经失败。氢键供体催化剂将允许底物活化，并应同时控制（立体）选择性。已经确定了可测试的选择性模型和策略，这将允许利用这一发现和改进的第二代催化剂的开发，以更好地促进这些转化，这在很大程度上完全超出了基准催化剂技术的范围。进一步的扩展，以扩大反应的范围，以最终的目标，使用酮作为亲电底物的协同催化的手段已被介绍。我们希望设计和制备一类新的手性有机催化剂，能够促进合成有用的不对称交叉偶姻反应的广泛范围，目前没有通用的和有效的对映选择性催化体系。

178 years after the Benzoin Condensation (BC) was discovered, a general, small molecule catalytic system for the cross-coupling of two different aldehyde molecules to generate enantioenriched α-hydroxy ketone products remains beyond our reach. We intend to instigate a systematic research programme aimed at addressing several challenges which have (in our view) stymied the progress of acyloin resp. benzoin chemistry over the past two centuries. Preliminary data and an analysis of models strongly indicate that a novel bifunctional chiral organocatalyst system developed in our groups would be capable of promoting a variety of asymmetric cross benzoin condensations (ACBC reactions) where other systems seem to have failed. The hydrogen-bond donating catalyst will allow for substrate activation and should simultaneously control (stereo)selectivity. A testable selectivity model and strategy has been identified which will allow the exploitation of this discovery and the development of modified 2nd generation catalysts to better promote these transformations, which for the most part are completely beyond the scope of benchmark catalyst technology. A further extension to broaden the scope of the reaction to the eventual goal of using ketones as electrophilic substrates by the means of cooperative catalysis has been introduced. We want to design and prepare a novel class of chiral organocatalyst capable of promoting synthetically useful asymmetric crossed acyloin reactions of wide scope, for which no general and efficient enantioselective catalytic system is currently available.