Cycloaddition of Thiourea- and Guanidine-Substituted Furans to Dienophiles: A Comparison of the Environmentally-Friendly Methods

Barešić, Luka; Margetić, Davor; Glasovac, Zoran

doi:10.3390/ecsoc-24-08380

Cited by 3 publications

(2 citation statements)

References 27 publications

(37 reference statements)

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“…We should emphasize that maleate derivative could also be formed but we limited our analysis to the formation of the more stable chlorofumarate 9 for the sake of simplicity. Deprotonation of the guanidinium cation by the chloride or iodide anion could be disregarded because we have shown that no aza-Michael addition products were obtained when N-phenylmaleimide was used instead of DMAD [25]. In this context, we could also note that the gas-phase basicities (GB) of 2-chlorofumarate and 2-chloromaleate anions calculated using B3LYP (1477 and 1469 kJ mol −1 , respectively) are significantly higher than that of chloride anions (1388 kJ mol −1 ; experimental value is 1374 kJ mol −1 [26]).…”

Section: Resultsmentioning

confidence: 99%

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

2023

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A proposed mechanism of the reaction of guanidinium chlorides with dimethyl acetylenedicarboxylate in a tandem aza-Michael addition reaction/intramolecular cyclization was investigated by DFT M06-2X and B3LYP computational approaches. The energies of the products were compared against the G3, M08-HX, M11, and wB97xD data or experimentally obtained product ratios. The structural diversity of the products was interpreted by the concurrent formation of different tautomers formed in situ upon deprotonation with a 2-chlorofumarate anion. A comparison of relative energies of the characteristic stationary points along the examined reaction paths indicated that the initial nucleophilic addition is energetically the most demanding process. The overall reaction is strongly exergonic, as predicted by both methods, which is primarily due to methanol elimination during the intramolecular cyclization step producing cyclic amide structures. Formation of a five-membered ring upon intramolecular cyclization is highly favored for the acyclic guanidine, while optimal product structure for the cyclic guanidines is based on a 1,5,7-triaza [4.3.0]-bicyclononane skeleton. Relative stabilities of the possible products calculated by the employed DFT methods were compared against the experimental product ratio. The best agreement was obtained for the M08-HX approach while the B3LYP approach provided somewhat better results than the M06-2X and M11 methods.

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Section: Resultsmentioning

confidence: 99%

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

2023

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“…Derivative 15 was obtained by base-catalyzed cyclization of the corresponding oxanorbornadiene [35]. Cycloadditions of N-Boc-furfurylamine with maleic anhydride and N-phenylmaleimide were conducted mechanochemically [50] and the analytical data for adduct 22 are identical to those prepared according to the literature [51]. The details are given in the Supplementary Materials.…”

Section: Methodsmentioning

confidence: 99%

Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline

Barešić,

Marijanović,

Dokli

et al. 2024

IJMS

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This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4–chloro– and 2–nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti–enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety.

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Anion-Controlled Synthesis of Novel Guanidine-Substituted Oxanorbornanes

Barešić

Margetić

Glasovac

2022

IJMS

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The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to the high nucleophilicity of guanidines, an aza-Michael reaction with dienophiles is more common and presents a huge obstacle in achieving the desired synthetic goal. Our preliminary investigations indicated that the proton could act as a suitable protecting group to regulate the directionality of the reaction. To investigate the role of the protonation state and type of anion, the reactivity of furfuryl guanidines with dimethyl acetylenedicarboxylate was explored. Furfuryl guanidines showed a strong reaction dependence on the nucleophilicity of the counterion and the structure of guanidine. While the reaction of DMAD with the guanidinium halides provided products of an aza-Michael addition, Diels–Alder cycloaddition occurred if non-nucleophilic hexafluorophosphate salts were used. Depending on the structure and the reaction conditions, oxanorbornadiene products underwent subsequent intramolecular cyclization. A tendency toward intramolecular cyclization was interpreted in terms of the pKa of different positions of the guanidine functionality in oxanorbornadienes. New polycyclic guanidines had a slightly decreased pKa in acetonitrile and well-defined geometry suitable for the buildup of selective sensors.

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Cycloaddition of Thiourea- and Guanidine-Substituted Furans to Dienophiles: A Comparison of the Environmentally-Friendly Methods

Cited by 3 publications

References 27 publications

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline

Anion-Controlled Synthesis of Novel Guanidine-Substituted Oxanorbornanes

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