Chair of Industrial Organic Chemistry and Biotechnology, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany.
Chem Commun (Camb). 2020 Mar 7;56(19):2885-2888. doi: 10.1039/c9cc09103c. Epub 2020 Feb 10.
In spite of the tremendous success of dynamic kinetic resolutions for a broad range of compound classes, tertiary alcohols and their corresponding esters have still remained as one of the most challenging substrates for this type of process. This is due to the size and steric hindrance of tertiary alcohols as well as to the difficulty in finding reaction conditions for the racemization of such compounds being at the same time compatible with the resolution reaction, which preferably is carried out with an enzyme. In this study, the first example of a dynamic kinetic resolution of a racemic tertiary alcohol is presented. The desired synthesis of the resulting enantiomerically pure ester was achieved by combining a lipase-catalyzed kinetic resolution with an in situ racemization utilizing a bio-compatible oxovanadium-catalyst. First, the two individual reactions were examined, improved and adjusted to be compatible with each other. Subsequently, addition of both catalysts in tailor-made portions led to the desired combined process and delivered the product with >99% ee and a conversion exceeding 50%, thus proving such a desired dynamic kinetic resolution of a tertiary alcohol.
尽管动力学拆分在广泛的化合物类别中取得了巨大的成功，但叔醇及其相应的酯类仍然是此类反应中最具挑战性的底物之一。这是由于叔醇的大小和空间位阻，以及寻找使这些化合物外消旋化的反应条件与分辨率反应兼容的困难，而分辨率反应最好是用酶进行的。在这项研究中，首次提出了对映体纯酯的外消旋叔醇的动力学拆分的实例。通过将脂肪酶催化的动力学拆分与利用生物相容的氧钒催化剂的原位外消旋化相结合，实现了所需的对映体纯酯的合成。首先，分别研究了这两个反应，对其进行了改进和调整，以使其相互兼容。随后，以定制的部分加入两种催化剂，导致所需的组合反应，并以超过 99%的 ee 和超过 50%的转化率得到产物，从而证明了这种叔醇的所需动力学拆分。
