Multi‐Photocatalyst Cascades: Merging Singlet Oxygen Photooxygenations with Photoredox Catalysis for the Synthesis of Alkaloid Frameworks

Abstract

The development of photocascades that rapidly transform simple and readily accessible furan substrates into polycyclic alkaloid frameworks or erythrina natural products is described. Each of the sequences developed makes use of photocatalyzed energy transfer processes, which generate singlet oxygen, to set up the substrates for the second photocatalyzed reaction, wherein electron transfer generates carbon‐centered radicals for the cyclizations that give the final complex frameworks. A chemical switch has been developed that can “switch off” one photocatalyst; thus, allowing a second photocatalyst to take over control of the sequence. As a corollary, this strategy represents the first time it has been possible to use multiple photocatalysts in photocascades, and, as such, it expands significantly the reactions that can be included in such cascades and the order in which they can be initiated.

The Rapid Synthesis of Colibactin Warhead Model Compounds Using New Metal‐Free Photocatalytic Cyclopropanation Reactions Facilitates the Investigation of Biological Mechanisms

“…Our initial task would be to synthesize a set of substrates 2 [13a,d,e] ready for the new cycloproponation reaction ( 2 → 3 ) so that it could be converted from concept to practical method. Later, we hoped to apply a chemical switch [13c,d] to the sequence beginning from furans of type 1 so that both the photochemical reactions ( 1 → 2 and 2 → 3 ) each using a different photocatalyst could be combined in a multiphotocatalyst cascade reaction sequence ( 1 → 3 in one pot). Once we had compounds of type 3 in hand, we suspected that the last steps (oxidation to complete the α,β‐unsaturated ketone unit and 1,4‐addition of substitutents R 1 ) might prove to be non‐trivial because much of the warhead's reactivity would now be in place and the compounds could begin to show enhanced instability, but we felt none of these issues were insurmountable.…”

“…Thus, we began by synthesizing a series of 5‐ylidene‐1 H ‐pyrrol‐2(5 H )‐ones 2 using our previously optimized conditions (Scheme 2). [13a,d,e] This one pot sequence begins with the addition of singlet oxygen (generated by a photosensitizer in the presence of visible spectrum light) to the furan core. Reduction and addition of a primary amine affords the corresponding 4‐pyrrolin‐2‐one [12] which then undergoes a second oxidation reaction facilitated by methylene blue; this time, however, no light is required as it is ground state methylene blue that is acting as the redox agent [12b] .…”

“…Scheme 1 outlines our strategy for the very rapid synthesis of a series of colibactin warhead analogs 5 . Our initial task would be to synthesize a set of substrates 2 [13a,d,e] ready for the new cycloproponation reaction ( 2 → 3 ) so that it could be converted from concept to practical method. Later, we hoped to apply a chemical switch [13c,d] to the sequence beginning from furans of type 1 so that both the photochemical reactions ( 1 → 2 and 2 → 3 ) each using a different photocatalyst could be combined in a multiphotocatalyst cascade reaction sequence ( 1 → 3 in one pot).…”

“…Photocatalytic cascades [29] are quite rare and usually rely on the repeated reaction of a single photocatalyst because of the inherent incompatibility of using different photocatalysts (due to cross quenching). Recently, we developed a chemical light switch in which an amine additive can be used to convert methylene blue (MB) from its photoactive form to its colorless inactive form, leucomethylene blue (LMBH), via reductive electron transfer (ET) [13c,d] . Once the MB has been switched off by its conversion to LMBH, the second photocatalyst can be switched on by irradiation with light.…”

Spontaneous generation of singlet oxygen on microemulsion-derived manganese oxides with rich oxygen vacancies for efficient aerobic oxidation

“…Singlet oxygen ( 1 O 2 ), recognized as a highly active and environmentally friendly reactive oxygen species (ROS), has garnered substantial attention from researchers in recent years. [1][2][3][4] Beneting from its remarkable oxidative capabilities and ecofriendliness, 1 O 2 has found widespread applications in green catalysis, [5][6][7] photocatalytic degradation, 8 tumor diagnosis and treatment, 9 and uorescence probes. 10 Nevertheless, the practical generation of 1 O 2 typically necessitates intense photoexcitation due to the spin transition between ground and excited state molecular oxygen.…”