Chemoselective Anaerobic Dehydrogenation of Alcohols by Using Visible Light and a Positively Charged Deazaflavin Catalyst Regenerated by Acetonitrile Solvent

DOI:10.1002/cctc.202401795

Abstract:
Three series of novel deazaflavinum salts differing in their substitutions at positions 5 (R = H, phenyl, or mesityl), 7, and 8 (R = OMe, Me, H, or Cl) were synthesized as potential catalysts of a novel chemoselective visible light-mediated anaerobic oxidation of primary and secondary alcohols to carbonyl compounds. This mild procedure uses acetonitrile as a solvent, which acts simultaneously as a sacrificial electron acceptor (in place of the oxygen usually used in photooxidation reactions), and therefore the reaction does not need any additives. Structure and properties-versus-catalytic activity studies identified 5-mesityl-7,8-dimethoxy-3-methyldeazaflavinium chloride (3a-Cl) as the most potent catalyst. 3a-Cl was effective in non-deuterated acetonitrile (CH₃CN), unlike its original 5-phenyl analogue 2a-Cl, which is efficient only in deuterated solvent (CD₃CN). This difference arises because the regeneration of the 2a-Cl catalyst is slower in CH₃CN than in CD₃CN. Our method using the optimized 3a-Cl photocatalyst and CH₃CN as a sacrificial oxidant and solvent in one is a useful addition to synthetic organic chemistry. Anaerobic conditions prevent side oxygenation reactions and overoxidations that usually occur in air or oxygen. This property makes this method suitable for dehydrogenations of alcohols that possess additional group(s) sensitive to oxygenation.

Chemoselective anaerobic dehydrogenation of primary and secondary alcohols to carbonyl compounds that leaves intact of additional oxygenation-sensitive functional groups is possible using a new flavin catalyst, 400 nm light, and acetonitrile, which acts simultaneously as a solvent and sacrificial oxidant. No other additives needed.

Fast singlet excited-state deactivation pathway of flavin with a trimethoxyphenyl derivative

DOI:10.1038/s41598-024-75239-x

Abstract:
Incorporation of the trimethoxyphenyl group at position 7 of flavin can drastically change the photophysical properties of flavin. We show unique fast singlet ¹(π,π*) excited state deactivation pathway through nonadiabatic transition to the ¹(n,π*) excited- state, and subsequent deactivation to the ground electronic state (S₀), closing the photocycle. This mechanism explains the exceptionally weak fluorescence and the short excited–state lifetime for the flavin trimethoxyphenyl derivative and the lack of excited triplet T₁ state formation. Full recovery of flavin in its ground state takes place within a 15 ps time window after photoexcitation in a polar solvent such as acetonitrile. According to quantum chemical calculations, the C₍₂₎-O distance elongates by 0.16 Å in the ¹(n,π*) state, with respect to the ground state. Intermediate–state structures are predicted by theoretical ab initio calculations and their dynamics are investigated using broadband vis-NIR time-resolved transient absorption and fluorescence up-conversion techniques.

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

DOI:10.3762/bjoc.20.161

Abstract:
Functionalized 5-aryldeazaalloxazines have been successfully synthesised through a one-pot, three-component reaction involving N,N-dimethylbarbituric acid, an aromatic aldehyde and aniline. By utilizing readily available reagents, this approach opens up the opportunity for the efficient formation of a variety of 5-aryldeazaalloxazines bearing electron-donating or halogen groups. This practical method is characterised by atom economy and offers a direct route to the introduction of an aryl moiety into the C(5)-position of deazaalloxazines, thereby generating novel catalysts for photoredox catalysis without the need for subsequent purification. Thus, it significantly improves existing approaches.

Ultrafast Events of Photoexcited Iron(III) Chloride for Activation of Benzylic C–H Bonds

DOI:10.1021/acs.jpclett.4c01116

Abstract:
The usage of rare-earth-metal catalysts in the synthesis of organic compounds is widespread in chemical industries but is limited owing to its environmental and economic costs. However, recent studies indicate that abundant-earth metals like iron(III) chloride can photocatalyze diverse organic transformations using blue-light LEDs. Still, the underlying mechanism behind such activity is debatable and controversial, especially in the absence of ultrafast spectroscopic results. To address this urgent challenge, we performed femtosecond time-resolved electronic absorption spectroscopy experiments of iron(III) chloride in selected organic solvents relevant to its photocatalytic applications. Our results show that the long-lived species [Fe(II) ← Cl^•]* is primarily responsible for both oxidizing the organic substrate and reducing molecular oxygen through the diffusion process, leading to the final product and regenerating the photocatalyst rather than the most widely proposed free chloride radical (Cl^•). Our study will guide the rational design of efficient earth-abundant photocatalysts.

Catalyst-free aerobic photooxidation of sensitive benzylic alcohols with chemoselectivity controlled using DMSO as the solvent

DOI:10.1039/D4GC00087K

Abstract:
The drawbacks commonly observed in synthetic methods for alcohol oxidation often stem from the utilization of complex, toxic, hazardous, or waste-producing oxidants. When sensitive or complex substrates bearing several functional groups are to be transformed, the selectivity of oxidation becomes another significant challenge. Herein, a chemoselective and operationally simple catalyst-free and additive-free method is presented for the aerial oxidation of 1-phenylpropargyl and 1-phenylallyl alcohols to their corresponding ketones, requiring only a solvent and visible light irradiation. The crucial role of dimethylsulfoxide (DMSO) as the solvent lies in achieving high chemoselectivity. Singlet oxygen, whose formation is photosensitized by the substrate and the product, is captured by DMSO, thereby preventing the undesired over-oxidation that occurs in other solvents. The application of DMSO to protect the substrate against singlet oxygen represents a novel approach that is potentially applicable to other aerobic photocatalytic processes.

Dicyanopyrazine photoredox catalysts: Correlation of efficiency with photophysics and electronic structure

DOI:10.1016/j.jcat.2024.115348

Abstract:
Catalytic performance of three structurally-related dicyanopyrazine catalysts has been investigated in three photoredox transformations including deuteration of aldehydes, cross-coupling of iodo-substituted (hetero)aromatic substrates, and α-hydrogen abstraction from amines followed by annulation to pyrroloquinoline. Significantly different catalytic activity of the photocatalysts has been explained with the aid of electrochemical, spectroscopic, and quantum-chemical methods. Electrochemical measurements pointed to reversible one-electron reduction of the photocatalysts affording the corresponding radical anion, and, therefore, dicyanopyrazines are principally well-suited for reductive quenching cycle. Triplet excited state turned out to be a major excited species employed in photoinduced electron transfer. The measured excited state reduction potentials (E_red* = +1.88/+1.43 V) classify the (5–methoxy)thiophene-substituted dicyanopyrazines among the organic photocatalysts with high oxidation power, which is in contrast to N,N-dimethylanilino-substituted photocatalysts. Whereas 5–methoxythiophene photocatalyst forms triplet excited state almost independently on the solvent polarity, transient absorption spectroscopy evidenced the triplet state of N,N-dimethylanilino derivative only in nonpolar media. Moreover, its subsequent reduction to the corresponding radical anion is chemically cumbersome, which contrast to facile one-electron reduction of both cyano groups of photocatalyst bearing weak 5–methoxythiophene donors. The doublet excited radical anion of the latter proved to be very powerful but short-lived reductant with E_ox* = –2.84 V. Its reduction power has been demonstrated in a cross-coupling reaction involving consecutive photoinduced electron transfer to preassociated iodo(hetero)arenes. Hence, bis(5-methoxythiophen-2-yl)-2,3-dicyanopyrazine can be utilized in photoredox catalysis either as powerful oxidant or reductant.

Exploring the Reactivity of Flavins with Nucleophiles Using a Theoretical and Experimental Approach

DOI:10.1002/cplu.202300547

Abstract:
Covalent adducts of flavin cofactors with nucleophiles play an important role in non-canonical function of flavoenzymes as well as in flavin-based catalysis. Herein, the interaction of flavin derivatives including substituted flavins (isoalloxazines), 1,10-ethylene-bridged flavinium salts, and non-substituted alloxazine and deazaflavin with selected nucleophiles was investigated using an experimental and computational approach. Triphenylphosphine or trimethylphosphine, 1-nitroethan-1-ide, and methoxide were selected as representatives of neutral soft, anionic soft, and hard nucleophiles, respectively. The interactions were investigated using UV/Vis and ¹H NMR spectroscopy as well as by DFT calculations. The position of nucleophilic attack estimated using the calculated Gibbs free energy values was found to correspond with the experimental data, favouring the addition of phosphine and 1-nitroethan-1-ide into position N(5) and methoxide into position C(10a) of 1,10-ethylene-bridged flavinium salts. The calculated Gibbs free energy values were found to correlate with the experimental redox potentials of the flavin derivatives tested. These findings can be utilized as valuable tools for the design of artificial flavin-based catalytic systems or investigating the mechanism of flavoenzymes.

The ability of flavin derivatives to add a nucleophile can be quantified and the regioselectivity estimated by Gibbs free energy values calculated by DFT methods. The theoretical data corresponds to the results obtained by ¹H NMR and UV/Vis spectroscopy and to experimental flavin reduction potentials.