One Photocatalyst, n Activation Modes Strategy for Cascade Catalysis: Emulating Coumarin Biosynthesis with (−)-Riboflavin

• Published in: Journal of the American Chemical Society 2016-01, Vol.138 (3), p.1040-1045
• Main Authors: Metternich, Jan B, Gilmour, Ryan
• Format: Article
• Language: English
• Subjects: Biocatalysis; Coumarins - chemistry; Coumarins - metabolism; Cyclization; Electron Transport; Energy Transfer; Molecular Conformation; Photochemical Processes; Riboflavin - chemistry; Riboflavin - metabolism; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.5b12081

Generating molecular complexity using a single catalyst, where the requisite activation modes are sequentially exploited as the reaction proceeds, is an attractive guiding principle in synthesis. This requires that each substrate transposition exposes a catalyst activation mode (AM) to which all preceding or future intermediates are resistant. While this concept is exemplified by MacMillan’s beautiful merger of enamine and iminium ion activation, examples in other fields of contemporary catalysis remain elusive. Herein, we extend this tactic to organic photochemistry. By harnessing the two discrete photochemical activation modes of (−)-riboflavin, it is possible to sequentially induce isomerization and cyclization by energy transfer (E T) and single-electron transfer (SET) activation pathways, respectively. This catalytic approach has been utilized to emulate the coumarin biosynthesis pathway, which features a key photochemical E → Z isomerization step. Since the ensuing SET-based cyclization eliminates the need for a prefunctionalized aryl ring, this constitutes a novel disconnection of a pharmaceutically important scaffold.