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

Abstract

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 (ET) 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.

Geometric E→Z Isomerisation of Alkenyl Silanes by Selective Energy Transfer Catalysis: Stereodivergent Synthesis of Triarylethylenes via a Formal anti‐Metallometallation

“…[1][2][3] Generating both E-a nd Z-substrate isomers is,h owever,o ften complicated by mechanistic and/or thermodynamic constraints, [4] requiring independent synthesis routes to be developed to prepare both substrates. [4,5,7,8] Predicated on selective energy transfer from an excited-state photosensitiser to the starting material, [4,5,9] this platform ensures that only the E-geometric isomer is activated. In the case of styrenyl systems that contain an embedded chromophore,e nergy transfer catalysis offers ap ractical activation method to achieve efficient geometrical E!Z isomerisation.…”

Visible-Light Photocatalytic E to Z Isomerization of Activated Olefins and Its Application for the Syntheses of Coumarins

“…Coumarins, the important structural motifs in natural products and bioactive compounds, exhibiting broad biological activities, have been the targets for many organic syntheses [32][33][34]. Among many successful methods developed over the years, cyclization of ortho-hydroxycinnamates via double-bond isomerization was the one which was generally convenient from easily obtained starting material and afforded the coumarins in very good yields.…”

Solvent-free, visible-light photocatalytic alcohol oxidations applying an organic photocatalyst

“…Furthermore, it was shown that the oxidation power of RFTA can be increased by coordination to scandium triflate [14]. Recently, the E / Z -isomerization of olefins with riboflavin as catalyst was reported [15], which was also used for cyclization to form coumarins [16]. …”