Presidential Young Investigator/Development of Chiral, Self-Replicating Molecules

自我繁殖是生命系统的核心特征，但在简单的化学系统中几乎是前所未有的。非手性α -杂醛与二烷基锌试剂的反应是一个很有希望研究的系统，可以在化学系统中启动这种能力的发展。二烷基锌加成醛通常是一个非常缓慢的反应，但可以被反应中产生的锌烷氧化物催化，因此这些体系表现出自催化行为。最近的研究表明，(R)-1-苯基丙醇（70%ee）的乙基锌盐催化二乙基锌加成苯甲醛，生成(R)-1-苯基丙醇（17%ee）。在该体系中，手性催化剂从非手性原料中生成自己的对映体，因为它必须复制自己，但反应的低对映选择性导致主要是外消旋混合物；对于二乙基锌与苯甲醛的加成反应，已经研制出了更好的对映选择性催化剂。它们都在醇氧化合物中加入了第二个配位，通常是一个氮。这项工作的目标是设计一个系统，其中一个非手性醛底物导致手性醇，这是一个有效的，对其自身形成的对映选择性催化剂。氨基醇催化体系最显著的特点之一是表现出正非线性效应。单体醇氧化物是活性催化剂，但它们在溶液中会二聚，生成非活性二聚体。最稳定的外消旋二聚体被有效地从催化体系中去除，从而提高了对映体的选择性。催化剂的单体和二聚体结构将被设计和建模，以产生积极的非线性效应。一个成功的反应体系将产生手性醇氧化合物，随着反应的进行，其对映体过量增加。斯科特·雷奇诺夫斯基博士获得了合成有机化学项目的总统青年研究员奖，以支持他开发手性、自我复制分子的研究。这项工作有可能彻底改变未来复杂手性分子的合成方式，并彻底改变化学家在攻击新结构时制定的战略计划的性质。

Self-reproduction is a central feature of living systems but is almost unprecedented in simple chemical systems. A promising system to be studied to initiate the development of such capacity in a chemical system is the reaction of an achiral alpha-heteroaldehyde with a dialkylzinc reagent. Dialkylzinc addition to aldehydes is normally a very slow reaction but can be catalyzed by the zinc alkoxides produced in the reaction and thus these systems show autocatalytic behavior. Recent studies showed that the ethylzinc salt of (R)-1-phenylpropanol (70%ee) catalyzes the addition of diethylzinc to benzaldehyde, producing (R)-1-phenylpropanol (17%ee). In this system the chiral catalyst generates its own enantiomer from achiral starting materials as it must to reproduce itself, but the reaction's low enantioselectivity leads to mainly a racemic mixture; much better enantioselective catalysts have been developed for the addition of diethylzinc to benzaldehyde. They all incorporate a second coordination site in the alkoxide, usually a nitrogen. The goal of this work is to design a system where an achiral aldehyde substrate leads to a chiral alkoxide which is an efficient, enantioselective catalyst for its own formation. One of the most remarkable features of the aminoalcohol catalyst systems is that they show a positive nonlinear effect. The monomeric alkoxides are the active catalysts, but they will dimerize in solution to give inactive dimers. The racemic dimer which is the most stable, is in effect removed from the catalytic system, thus increasing the enantioselectivity. Monomeric and dimeric structures of the catalysts will be designed and modeled to produce a positive nonlinear effect by this mechanism. A successful reaction system will produce a chiral alkoxide with increasing enantiomeric excess as the reaction proceeds. Dr. Scott Rychnovsky is being given the Presidential Young Investigator Award from the Synthetic Organic Chemistry Program to support his research to develop chiral, self-replicating molecules. This work has the potential to revolutionize how the complex chiral molecules will be synthesized in the future and completely change the nature of the strategic plans that are developed by the chemist in attacking new structures.