Alkylations of simple electron‐rich heterocompounds deliver valuable target structures in bioorganic and medicinal chemistry. Herein, we present a straightforward and photosensitizer free approach ...for the photoinduced C–C coupling of electron‐rich unsaturated heterocompounds with alkyl bromides using 405 nm and 365 nm irradiation. Comprehensive mechanistic studies indicate the involvement of 2,6‐lutidine in the formation of a non‐covalently bound intermediate to which the function of a photosensitizer is attributed. UV/Vis spectra reveal the formation of a bathochromic shifted band when the electron‐deficient alkyl bromide is mixed with the structural motif of 2,6‐substituted pyridine. Upon photochemical excitation of this band, we find the initiation of the C–C bond‐forming reaction. Using this approach highly versatile alkylation products, e.g. α‐substituted ketones and 2‐substituted furan, thiophene, and pyrrole derivatives, are obtained in high selectivity. Furthermore, this synthetic methodology can be applied to access substituted indoles, which cannot be obtained by other transformations.
No need for a complex photosensitizer: We introduce a method for selective photoinduced alkylations of electron‐rich heterocompounds with electron‐deficient allyl bromides in the presence of 2,6‐lutidine at 365 or 405 nm. Mechanistic investigations reveal that a colored intermediate formed from 2,6‐lutidine and alkyl bromide is involved in the photoactivation. Our approach uses commercially available reagents and a straightforward protocol.
Kinetics of the reactions of aryldiazomethanes (ArCHN2) with benzhydrylium ions (Ar2CH+) have been measured photometrically in dichloromethane. The resulting second-order rate constants correlate ...linearly with the electrophilicities E of the benzhydrylium ions which allowed us to use the correlation lg k = s N(N + E) (eq 1) for determining the nucleophile-specific parameters N and s N of the diazo compounds. UV–vis spectroscopy was analogously employed to measure the rates of the 1,3-dipolar cycloadditions of these aryldiazomethanes with acceptor-substituted ethylenes of known electrophilicities E. The measured rate constants for the reactions of the diazoalkanes with highly electrophilic Michael acceptors (E > −11, for example 2-benzylidene Meldrum’s acid or 1,1-bis(phenylsulfonyl)ethylene) agreed with those calculated by eq 1 from the one-bond nucleophilicities N and s N of the diazo compounds and the one-bond electrophilicities of the dipolarophiles, indicating that the incremental approach of eq 1 may also be applied to predict the rates of highly asynchronous cycloadditions. Weaker electrophiles, e.g., methyl acrylate, react faster than calculated from E, N, and s N, and the ratio of experimental to calculated rate constants was suggested to be a measure for the energy of concert ΔG ‡ concert = RT ln(k 2 exptl/k 2 calcd). Quantum chemical calculations indicated that all products isolated from the reactions of the aryldiazomethanes with acceptor substituted ethylenes (Δ2-pyrazolines, cyclopropanes, and substituted ethylenes) arise from intermediate Δ1-pyrazolines, which are formed through concerted 1,3-dipolar cycloadditions with transition states, in which the C–N bond formation lags behind the C–C bond formation. The Gibbs activation energies for these cycloadditions calculated at the PCM(UA0,CH2Cl2)/(U)B3LYP-D3/6-31+G(d,p) level of theory agree within 5 kJ mol–1 with the experimental numbers showing the suitability of the applied polarizable continuum model (PCM) for considering solvation.
The Front Cover shows the photosensitizer free, photoinduced C–C coupling of electron‐rich unsaturated heterocompounds with alkyl bromides using 405 nm and 365 nm irradiation. More information can be ...found in the Communication by O. Trapp et al.
Organocatalysis is a powerful approach to extend and (enantio‐) selectively modify molecular structures. Adapting this concept to the Early Earth scenario offers a promising solution to explain their ...evolution into a complex homochiral world. Herein, we present a class of imidazolidine‐4‐thione organocatalysts, easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. These imidazolidine‐4‐thiones are readily formed from mixtures of aldehydes or ketones in presence of ammonia, cyanides and hydrogen sulfide in high selectivity and distinct preference for individual compounds of the resulting catalyst library. These organocatalysts enable the enantioselective α‐alkylation of aldehydes under prebiotic conditions and show activities that correlate with the selectivity of their formation. Furthermore, the crystallization of single catalysts as conglomerates opens the pathway for symmetry breaking.
Kick‐start for the origin of life: A class of imidazolidine‐4‐thione organocatalysts has been identified enabling enantioselective α‐alkylation of aldehydes under prebiotic conditions. These catalysts are easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. Remarkably, they crystallize as conglomerate facilitating the process of spontaneous symmetry breaking.
Alkylations of simple electron‐rich heterocompounds deliver valuable target structures in bioorganic and medicinal chemistry. Herein, we present a straightforward and photosensitizer free approach ...for the photoinduced C–C coupling of electron‐rich unsaturated heterocompounds with alkyl bromides using 405 nm and 365 nm irradiation. Comprehensive mechanistic studies indicate the involvement of 2,6‐lutidine in the formation of a non‐covalently bound intermediate to which the function of a photosensitizer is attributed. UV/Vis spectra reveal the formation of a bathochromic shifted band when the electron‐deficient alkyl bromide is mixed with the structural motif of 2,6‐substituted pyridine. Upon photochemical excitation of this band, we find the initiation of the C–C bond‐forming reaction. Using this approach highly versatile alkylation products, e.g. α‐substituted ketones and 2‐substituted furan, thiophene, and pyrrole derivatives, are obtained in high selectivity. Furthermore, this synthetic methodology can be applied to access substituted indoles, which cannot be obtained by other transformations.
Organocatalysis is a powerful approach to extend and (enantio‐) selectively modify molecular structures. Adapting this concept to the Early Earth scenario offers a promising solution to explain their ...evolution into a complex homochiral world. Herein, we present a class of imidazolidine‐4‐thione organocatalysts, easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. These imidazolidine‐4‐thiones are readily formed from mixtures of aldehydes or ketones in presence of ammonia, cyanides and hydrogen sulfide in high selectivity and distinct preference for individual compounds of the resulting catalyst library. These organocatalysts enable the enantioselective α‐alkylation of aldehydes under prebiotic conditions and show activities that correlate with the selectivity of their formation. Furthermore, the crystallization of single catalysts as conglomerates opens the pathway for symmetry breaking.
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