Journal of Organic Chemistry最新文献

Functionalized S-aryl thioimidates were synthesized from thioamides and arylboronic acids at room temperature under mild conditions. The reaction was catalyzed by copper(II) acetate in the presence of DBU under an open atmosphere. A wide range of functionalized aryl and alkyl boronic acids was chemo-selectively coupled with aryl and alkyl thioamides to obtain corresponding S-aryl and S-alkyl thioimidates in 64-80% yields. Room temperature reactions, easy operation, and broad substrate scope are the salient features of the developed methodology.

The C5-C11 moiety of phoslactomycin I-i was synthesized via chelation-controlled addition of CH₂═CHMgBr to the C8 ketone, ozonolysis, and the HWE reaction. The TMS acetylene and C1-C4 were attached to C11 and C5, respectively. A cyclohexyl moiety possessing an iodovinyl group was synthesized from quinic acid. The coupling reaction of the intermediates followed by Zn reduction yielded the cis,cis-diene. Finally, the amino and phosphate groups were attached.

Alpha-pyrones have been used for applications ranging from total synthesis to antibiotics. However, their application as dienes in bioorthogonal reactions has not been extensively explored. In previous work, we demonstrated the promising application of ester-functionalized pyrones in bioorthogonal protein labeling. Here, we constructed a library of substituted pyrones to evaluate their potential in bioorthogonal reactions by exploring the relationships among structure, reactivity, and bioorthogonality. We found that most pyrone derivatives with electron-withdrawing groups exhibited reactivity toward endo-bicyclo[6.1.0]nonyne (BCN), producing tricyclic and tetracyclic products in good yields. As expected, pyrones with more and stronger electron-withdrawing substituents showed faster reaction kinetics with BCN. Bicyclic pyrone derivatives showed substantially decreased reactivity, most likely resulting from increased steric effects. Counterintuitively, we found that substitutions at pyrone positions 4 and 5 affected the reactivity more than those at positions 3 and 6. To provide insights into both the expected and counterintuitive reactivities of the pyrone library members, we performed a quantum chemical analysis. Additionally, we evaluated each pyrone's reactivity with L-cysteine and found no correlation between pyrone reactivity with BCN and cysteine-based bioorthogonality. Finally, we evaluated the reactivity of pyrones toward a collection of popular dienophiles used in bioorthogonal reactions.

The stereoselective oxidation of benzoazepine-fused isoindolines to benzoazepine-fused isoindole atropodiastereomers is investigated, revealing a central-to-axial chirality conversion. By leveraging the characteristic folded conformation of these C-N atropisomers, Diels-Alder cycloaddition of the isoindole is achieved with complete facial selectivity, generating sp³-rich structures as single isomers.

A novel [3+3] cyclization reaction between phenol and hydrazone was successfully developed under electrochemically driven conditions. This reaction provided access to a diverse array of 1,3,4-oxadiazinane compounds in consistently high yields, reaching up to 87%. Notably, the reaction exhibited remarkable tolerance toward a broad spectrum of both phenol and hydrazone substrates, underscoring its versatility. Moreover, the protocol distinguished itself by its exceptional atom and step economy, facilitating the efficient construction of functionalized 1,3,4-oxadiazines. The synthetic utility of this approach was further exemplified by its scalability, as demonstrated by gram-scale reactions, and its broad substrate scope.

In this paper, micellar-mediated synthesis of chalcones was explored. After optimization of the reaction conditions, the cationic surfactant CTAB and the nonionic one, Tween 80, were taken into consideration. Both surfactants were used to study the scope of Claisen-Schmidt reactants, and a wide scope on both aromatic aldehydes and methyl ketones was explored, obtaining from good to very good yields in most cases and thus demonstrating that the chalcones can be proficiently synthesized in micellar solutions with a wide functional group tolerability. Often, when one surfactant did not perform well, the other surfactant performed better, demonstrating that the use of different surfactants can constitute a good alternative to overcome reactivity problems. Besides, Tween 80 can be proposed as a good and greener alternative to CTAB in most cases. Some reactions gave low yields, showing that some specific improvements would be needed to address the low reactivity. The micellar medium was studied by NMR to search for information about the association of the Claisen-Schmidt reactants with the micelles and their locations within them. Diffusion Ordered Spectroscopy (DOSY) was applied to assess the interaction and the percentage of incorporation of reactants into the micelles.

We present a new strategy for the synthesis of O-aryl glycosides through the formal insertion of glycosylidene carbenes into the O-H bond of phenols. The key glycosylidene carbene intermediates were generated in situ by copper-catalyzed oxidation of bench-stable glycosylidene diaziridine precursors. This method enables the glycosylation of a variety of phenols with good yields, excellent diastereoselectivity, and chemoselectivity, providing a highly practical method for the late-stage glycosylation of complex natural products and bioactive agents.