Carbonylative Hydroacylation of Styrenes with Alkyl Halides by Multiphoton Tandem Photoredox Catalysis in Flow

Abstract

The abundance, structural diversity, and versatility of ketones give prominence to this carbonyl functional group in synthetic chemistry. The assembly of ketones via the carbonylative hydroacylation of alkenes represents a powerful modular strategy for the synthesis of unsymmetric ketone products. Here, we report the photocatalytic carbonylative hydroacylation of styrenes with unactivated alkyl halides. This protocol unifies the visible-light multiphoton catalytic cycle of [Ir­(ppy)2(dtb-bpy)]+ with flow chemistry to engage energy-demanding alkyl bromides and iodides at moderate pressures of carbon monoxide. The mild and practical methodology was employed to prepare a diverse array of 44 unsymmetric dialkyl ketones from primary, secondary, and tertiary unactivated alkyl halides. We demonstrate the application of flow chemistry technology to achieve spatially resolved chemoselectivity and broad functional group tolerance for the mild generation of functionalized C­(sp3)-rich ketone products.

Selective Mono‐Defluorinative Cross‐Coupling of Trifluoromethyl arenes via Multiphoton Photoredox Catalysis

“…This observation strongly suggests the formation a new type of photocatalyst that possesses the higher reductive potential to reduce trifluorotoluene, which is also characterized by Knowles' recent work. [41] Based on a previous report [37,41] and our results, the following mechanism is proposed (Figure 3). First, trifluorotoluene is reduced by the highly reducing multiphoton excited state [Ir2] 0 *, forming a trifluorotoluene radical anion I.…”

“…The initially recorded emission spectra showed that a new type of photocatalyst was formed upon irradiation of (Ir[dF(CF 3 )ppy] 2 (dtbpy))PF 6 in the presence of diisopropylamine (Figure 1a), which is also in line with the findings reported by the Knowles group. [41] Thus, we decided to apply this catalyst in the selective mono-defluorinative crosscoupling of multiphoton photoredox catalysis (Figure 1b).…”

Photo‐induced Multiphasic Reactions in Flow Process: A Decade of Progress

“…In 2022, the Polyzos group also published research on a photocatalytic carbonylative hydroacylation by using styrene and alkyl halides. [35] This innovative protocol combines visiblelight multiphoton catalysis with flow chemistry, enabling the utilization of energy-demanding alkyl bromides and iodides at moderate CO pressures to synthesize unsymmetrical ketone compounds, which hold considerable importance in the pharmaceutical industry and the creation of complex natural products. [36] A key aspect of this approach is the use of continuous flow technology to precisely introduce super-stoichiometric amounts of carbon monoxide into the reaction mixture, ensuring safety and enhancing the efficiency of the photochemical processes.…”

“…In 2022, the Polyzos group also published research on a photocatalytic carbonylative hydroacylation by using styrene and alkyl halides [35] . This innovative protocol combines visible‐light multiphoton catalysis with flow chemistry, enabling the utilization of energy‐demanding alkyl bromides and iodides at moderate CO pressures to synthesize unsymmetrical ketone compounds, which hold considerable importance in the pharmaceutical industry and the creation of complex natural products [36]…”

Extending Photocatalyst Activity through Choice of Electron Donor

“…The new, partially reduced complex [Ir­(ppy) 2 (H 3 -dtbbpy)], characterized by a striking hypsochromic shift in emission energy, then works in tandem with the original catalyst to engage energy demanding substrates (Figure b). While the tandem photocatalysis of [Ir­(ppy) 2 (H 3 -dtbbpy)] facilitates numerous synthetic reactions, − the same transformation in other cationic iridium­(III) complexes can decrease the available catalytic energy . The delicate balance between photochemical stability and reactivity in this and other multiphoton catalysis systems is poorly understood and may limit selectivity and reusability, which is particularly important for precious metal complexes.…”