A research team led by Prof. Do Hyun RYU (Dept. of Chemistry) has developed the first catalytic synthetic method of chiral 2,5-dihydrooxepine.



2,5-Dihydrooxepine, seven-membered cyclic compound containing oxygen atom, is a structural core of many important natural products. Therefore, a variety of synthetic methods have been widely developed for several decades. However, there has been no example of catalytic asymmetric synthesis of 2,5-dihydrooxepines and multiple synthetic steps were required to prepare corresponding starting materials.



The research team developed asymmetric synthetic method of highly functionalized 2,5-dihydrooxepine with chiral Lewis acid catalyst through cyclopropanation/retro-Claisen rearrangement tandem reaction to give good yields and high enantioselectivity. Developed methodology exhibits excellent atom economy because this utilizes simple starting materials and nitrogen gas (N2) is the only by-product. Since there are various bioactive natural products which possess dihydrooxepine as a key structure, chiral 2,5-dihydrooxepine derivatives synthesized with developed method are expected to be used in bio- or medicinal chemistry fields.



Prof. RYU said "the value of this work is to synthesize enantioenriched 2,5-dihydrooxeines from simple starting materials using catalyst. Furthermore, this work is highly valuable because this suggests experimental results to support computational calculation data about reaction mechanism of retro-Claisen rearrangement of cyclopropane to 2,5-dihydrooxepine."



This research was published in the Angewandte Chemie International Edition (IF : 11.709) as of April 18th, with the title of "Catalytic Enantioselective Synthesis of 2,5-Dihydrooxepines" (doi: 10.1002/anie.201700890). This work was selected as a Very Important Paper (VIP) and front cover page of July 17th.