The Journal of Organic Chemistry最新文献

A copper-catalyzed intramolecular synthesis of 3-alkenyl-2H-indazoles from 2-alkynylazobenzenes is described. The reaction proceeds in a single step via C–N bond formation and a subsequent 1,2-hydride shift, affording products in high yields. DFT calculations suggest the 1,2-hydride shift as the rate-determining step. Further derivatization enables functionalization of the 3-alkenyl-2H-indazoles.

Herein, we report a metal-free light-induced three-component reaction for the synthesis of polychloroalkyl-substituted quinoxalin-2(1H)-ones using commercially available alkenes, polyhalo alkanes, and quinoxalin-2(1H)-ones. Preliminary mechanistic studies suggested the generation of radical intermediates via an EDA-complex, single electron transfer, or halogen atom transfer pathway. Under mild reaction conditions, various alkenes and quinoxalin-2(1H)-ones containing different functional groups are compatible, providing the corresponding polychloroalkyl-substituted quinoxalin-2(1H)-ones in moderate to good yields.

A new sulfonyl fluoride reagent 1-bromobut-3-ene-1,3-disulfonyl difluoride (BEDF) was developed. This unique reagent possesses two clickable functionalities to be used for both azide–alkyne cycloaddition click and SuFEx click reactions. This new reagent was applied for the regioselective construction of a class of novel triazolyl vinyl sulfonyl fluorides in which the C-4 position 1H-1,2,3-triazoles were functionalized with vinyl sulfonyl fluorides of exclusively E-configuration.

Aryl sulfonyl fluorides are prominently featured in organic synthesis and medicinal chemistry. Herein, a metal-free photoredox-catalyzed three-component assembly of aryl sulfonyl fluoride via aryl sulfonyl ammonium salt intermediate has been reported. A variety of structurally diverse aryl sulfonyl fluorides were synthesized rapidly from dibenzothiophenium (DBT) salts under mild conditions by using KHF₂ as the fluorine source. Notably, this methodology can be employed as an efficient and sustainable approach for late-stage drug fluorosulfonylation. Good yields and broad functionality tolerance were the features of this methodology. Moreover, the derivatization of aryl sulfonyl fluoride molecules was also demonstrated to showcase its synthetic utility.

A novel and straightforward method for the iron-catalyzed regioselective cross-dehydrogenative coupling of para-quinone methides (p-QMs) with formamides has been developed, facilitated by the in situ activation of the C(sp²)–H bonds of the formyl and alkenyl substituents via a radical strategy. This method does not require the preactivation of the substrates, and it can accommodate a wide range of p-QMs and formamides under the optimized reaction conditions, resulting in the formation of the expected C-7 acetamides-functionalized para-quinone methides with moderate to good yields. The control experiments revealed that the reaction follows the fundamental equation of second-order kinetics. Additionally, an exploration of the Hammett effect was undertaken to elucidate the impact of the substituents for the reaction. In combination with the DFT calculation, a plausible reaction mechanism was proposed through meticulously controlled experiments.

The β-amino ketones produced through the Mannich reaction hold significant potential as candidates for various drugs. In this study, we optimized on-DNA Mannich reaction conditions and applied them to investigate the reactions of DNA-conjugated aldehydes with various amine and ketone building blocks. The developed on-DNA Mannich reaction preserved the DNA integrity and established viable routes for library production. These results underscore the potential of the Mannich reaction in DNA-encoded library (DEL) synthesis.

A photocatalytic three-component cascade reaction of readily available enaminones, hydrazines, and CBr₄ for the synthesis of bromo-substituted pyrazoles in one pot has been demonstrated. This strategy involves intermolecular C-N/C-Br bond formation and represents an efficient approach to the construction of 4-bromo-substituted pyrazoles with high regioselectivity, broad substrate scope, good functional group tolerance, convenient operation, and mild reaction conditions. Mechanistic investigations show that this reaction proceeds via intermolecular cyclization of enaminones with hydrazines, followed by a regioselective bromination of pyrazoles using CBr₄ as a “Br” source.

A concise synthesis of (2R,6R)-hydroxynorketamine was accomplished in eight steps, starting from commercially available materials. This synthesis features a cerium chloride-enhanced Stork–Danheiser reaction, an asymmetric reduction of ketone by the Corey–Bakshi–Shibata reaction, a signature Overman rearrangement, and a facial selective dihydroxylation of an electronically deficient olefin by RuCl₃/NaIO₄. The overall yield is 7.3% with 94.5% ee.

A practical approach for rapid and efficient access to spirocyclic isobenzofurans is described. The reaction proceeds through the cycloaddition of 1,6-ynenone derivatives and 4-nitro-1,3-diarylbutan-1-ones, promoted by Cs₂CO₃ in the presence of l-proline as a catalyst. The advantages of this reaction include the formation of two C–C bonds and one C–O bond as well as mild reaction conditions. Extended spirocyclic isobenzofurans are obtained with good efficiency and diastereoselectivity under these mild conditions, and this new protocol avoids the use of any transition-metal reagents.

In situ 1D NMR spectroscopic reaction monitoring allows detailed investigation of chemical kinetics and mechanism. Concentration versus time data are derived from a time series of NMR spectra. Each spectrum in the series is obtained by Fourier transform of the corresponding FID. When the spectrometer outputs FIDs recorded from multiple scans, the spectra benefit from an increase in signal-to-noise (S/N). However, this reduces the number of FIDs and, thus, kinetic data points. We report a simple alternative in which the same number of scans is acquired by the spectrometer, but each scan is saved independently. Signal averaging is then conducted by postacquisition processing. This leads to an increase in both the S/N and the number of kinetic data points and can avoid “overaveraging” effects. The entire series of single-scan FIDs spanning the reaction lifetime can be summed to yield a “total reaction spectrum” in which intermediates can be identified. The method can be applied in coherence with phase cycling to minimize spectral distortion during solvent signal suppression. Overall, the approach simplifies the preacquisition parameters to the estimation of the reaction duration and T₁^max and then the selection of the pulse angle, θ, and scan repetition time, τ_R, without the need to set the signal averaging before the experiment.