Piperidines are an important pharmacophore and essential in the field of drug discovery. Piperidine scaffolds are the building blocks for over 70 different types of commercial drugs, and have a wide range of therapeutic applications. The overarching goal of this project is to develop a robust catalytic, asymmetric synthesis of piperidine rings from feedstock chemicals. In one initial study of the Pictet-Spengler cyclization with N-para-toluenesulfonyl and N-tert-butanesulfonyl homoveratrylamine and 3-phenylpropanal, a screen of metal triflates was examined. Initial results indicated that scandium (III), stannous (II) and copper (II) triflates gave the fastest conversion to the N-sulfonyl piperidine, while triflates such as lanthanum (III), sodium (I) and magnesium (II) gave little to no conversion under the allotted time. However, the triflates that proved successful with N-Ts homoveratrylamine did not produce the same conversion when screened against N-Bus homoveratrylamine. Based upon accepted knowledge of the mechanism we propose that the cyclization proceed through an N-sulfonyliminium ion intermediate. In a second investigation, N-sulfonamides derived from tryptamine were examined with metal triflates. Future studies will focus on the use of chiral ligands to induce asymmetry in the cyclization event. These experiments will examine enantioselectivity of the Pictet-Spengler cyclization in comparison to earlier results with analysis by chiral HPLC.

Investigation of acid catalyzed Pictet-Spengler cyclization with sulfonamides

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.