A research team led by Prof. Do Hyun RYU (Dept. of Chemistry) has developed Lewis acid catalyzed asymmetric synthetic method of cyclobutanones.

Chiral four-membered carbocyclic compounds are key structures of bioactive natural products. Therefore, they have attracted a lot of attention in the academic and industrial world. Although four-membered carbocyclic ketone compounds can be obtained from cyclopropane compounds through ring-opening reactions, there has been no example of asymmetric synthesis of cyclobutanones from cyclopropyl aldehydes through rearrangement reactions.

The research team developed asymmetric synthetic method of cyclobutanones with chiral Lewis acid catalyst through tandem cyclopropanation/semipinacol rearrangement reaction to give good yields and high enantioselectivities. The newly developed methodology exhibits excellent atom economy because it utilizes simple starting materials and only produces nitrogen gas (N2) as a by-product.

Prof. RYU said, “the synthesis of chiral cyclobutanone compounds through rearrangement of cyclopropyl aldehydes has been an unresolved challenge for the last 50 years. This work is highly valuable because this is the first research result with a catalyst and provides experimental results to elucidate the reaction mechanism.”

Cyclobutanones are highly useful compounds because they can be utilized in ring expansion or ring opening reactions due to their innate ring strain. In this regard, this synthetic method is expected to be valuable synthetic tool for further organic synthesis.

This research was published in the ‘Journal of the American Chemical Society (JACS; IF : 14.357)’ as of August 8th, 2018, with the title of “Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semipinacol Rearrangement”. This work was selected as the cover page.