Determining enantiomeric excess (e.e.) in chiral compounds is key to development of chiral catalyst auxiliaries and chiral drugs. Here we describe a sensitive and robust fluorescence-based assay for determining e.e. in mixtures of enantiomers of 1,2- and 1,3-diols, chiral amines, amino alcohols, and amino-acid esters. The method is based on dynamic self-assembly of commercially available chiral amines, 2-formylphenylboronic acid, and chiral diols in acetonitrile to form fluorescent diastereomeric complexes. Each analyte enantiomer engenders a diastereomer with distinct fluorescence wavelength/intensity originating from enantiopure fluorescent ligands. In this assay, enantiomers of amines and amine derivatives assemble with diol-type ligands containing a binaphthol moiety (BINOL and VANOL), whereas diol enantiomers form complexes with the enantiopure amine-type fluorescent ligand tryptophanol. The differential fluorescence is utilized to determine the amount of each enantiomer in the mixture with an error of <1% e.e. This method enables high-throughput real-time evaluation of enantiomeric/diastereomeric excess (e.e./d.e.) and product yield of crude asymmetric reaction products. The procedure comprises high-throughput liquid dispensing of three components into 384-well plates and recording of fluorescence using an automated plate reader. The approach enables scaling up the screening of combinatorial libraries and, together with parallel synthesis, creates a robust platform for discovering chiral catalysts or auxiliaries for asymmetric transformations and chiral drug development. The procedure takes ~4–6 h and requires 10–20 ng of substrate per well. Our fluorescence-based assay offers distinct advantages over existing methods because it is not sensitive to the presence of common additives/impurities or unreacted/incompletely utilized reagents or catalysts.

确定手性化合物中的对映体过量（ee）是开发手性催化剂助剂和手性药物的关键。在这里，我们描述了一种灵敏且稳健的基于荧光的测定方法，用于确定1,2-和1,3-二醇，手性胺，氨基醇和氨基酸酯的对映异构体混合物中的ee。该方法基于市售手性胺，2-甲酰基苯基硼酸和手性二醇在乙腈中的动态自组装，以形成荧光非对映体复合物。每种分析物对映异构体产生非对映异构体，其具有源自对映体纯荧光配体的不同荧光波长/强度。在此分析中，胺和胺衍生物的对映异构体与含有联萘酚部分的二醇型配体（BINOL和VANOL）组装在一起，而二醇对映异构体与对映纯胺型荧光配体色氨酸组成络合物。利用差分荧光来确定混合物中每种对映体的数量，误差<1％ee产品。该过程包括将三种组分的高通量液体分配到384孔板中，并使用自动酶标仪记录荧光。该方法可以扩大组合文库的筛选，并与平行合成一起，为发现用于不对称转化和手性药物开发的手性催化剂或助剂创造了一个强大的平台。该过程大约需要4-6小时，每孔需要10-20 ng底物。我们的基于荧光的测定法与现有方法相比具有明显的优势，因为它对常见的添加剂/杂质或未反应/使用不完全的试剂或催化剂不敏感。