Efficient C(sp³)−H Carbonylation of Light and Heavy Hydrocarbons with Carbon Monoxide via Hydrogen Atom Transfer Photocatalysis in Flow**

Abstract

Despite their abundance in organic molecules, considerable limitations still exist in synthetic methods that target the direct C−H functionalization at sp3‐hybridized carbon atoms. This is even more the case for light alkanes, which bear some of the strongest C−H bonds known in Nature, requiring extreme activation conditions that are not tolerant to most organic molecules. To bypass these issues, synthetic chemists rely on prefunctionalized alkyl halides or organometallic coupling partners. However, new synthetic methods that target regioselectively C−H bonds in a variety of different organic scaffolds would be of great added value, not only for the late‐stage functionalization of biologically active molecules but also for the catalytic upgrading of cheap and abundant hydrocarbon feedstocks. Here, we describe a general, mild and scalable protocol which enables the direct C(sp3)−H carbonylation of saturated hydrocarbons, including natural products and light alkanes, using photocatalytic hydrogen atom transfer (HAT) and gaseous carbon monoxide (CO). Flow technology was deemed crucial to enable high gas‐liquid mass transfer rates and fast reaction kinetics, needed to outpace deleterious reaction pathways, but also to leverage a scalable and safe process.

Solar‐Driven Continuous CO2 Reduction to CO and CH4 using Heterogeneous Photothermal Catalysts: Recent Progress and Remaining Challenges

“…Two of the main reactions focused on in CO 2 reduction are the Sabatier reaction (Reaction 1) for methane (CH 4 ) production and the reverse water gas shift (RWGS) reaction (Reaction 2) [14–18] . In the RWGS reaction carbon monoxide (CO) is produced, which can be used as feedstock for producing chemicals and fuels (e. g., methanol and Fischer‐Tropsch hydrocarbons) [19–23] . However, the use of high temperatures and pressures in combination with the use of non‐sustainable energy in classical thermal processes encourages novel research to find alternative approaches [24,25] .…”

Multiphasic Continuous‐Flow Reactors for Handling Gaseous Reagents in Organic Synthesis: Enhancing Efficiency and Safety in Chemical Processes

“…A related work by Noël and co-workers demonstrated the use of Taylor flow for the photocatalytic carbonylation of light/heavy alkanes to synthesize unsymmetrical ketones (Scheme 8B). [58] Gaseous light alkanes and toxic carbon monoxide gas are handled as a gas-gas-liquid mixture inside microchannels, to improve mass transfer and create a safe environment for the direct activation of light alkanes. Scheme 6.…”

“…[55] B) Efficient mass transfer in gas-gas-liquid Taylor flow for the photocatalytic carbonylation of light/heavy alkanes. [58] Figure 5. Corning Lab Reactor: microchip with internal static mixers for improved mass transfer in biphasic reactions.…”

Unraveling the Prominent Existence of Trace Metals in Photocatalysis: Exploring Iron Impurity Effects

“…In pursuit of replacing high-performance photocatalysts typically based on iridium or ruthenium, catalysts based on earth-abundant metals , or organic molecules have been successfully utilized in various transformations, and offer a rich mechanistic landscape for generating open-shell species. In particular, the exploration of 3 d -metal complexes as photocatalysts provides a simple method for generating highly active chlorine- and oxygen-centered radicals via ligand-to-metal charge transfer (LMCT), facilitating the cleavage of strong C­(sp 3 ) -H bond. , After decades of pioneering work by Kochi, Shulpin, and Ken Takaki, LMCT photochemistry has emerged as a powerful tool for C­(sp 3 )-H bond functionalization, and the photochemically active metal complexes have expanded from Cu­(II) and Fe­(III), ,− to Ni­(III), − Ce­(IV), , Ti­(IV), and Bi­(III) . Moreover, remarkable catalyst efficiency was observed in inert C­(sp 3 )–H bond functionalization of alkanes with electron-deficient olefins or azodicarboxylates, involving Fe­(III) (reported by Duan, Jin, − and Gong, respectively) and Ce­(IV) complexes (reported by Zuo, Walsh, and Schelter, respectively) (Figure b).…”