Synlett最新文献

We have developed a TfOH-catalyzed, highly efficient protocol for the synthesis of biologically active β-acylamino ketones from aldehyde, ketone, and nitrile by avoiding the use of acetyl chloride. The reaction proceeds through a sequential aldol reaction followed by a nucleophilic attack of nitrile and hydrolysis of nitrile in one pot. The attractive features of this tandem process are mild reaction conditions, high atom economy, broad substrate scope with 51–87% yield, gram-scale reaction, and ease of operation.

Azo compounds with a high density, high enthalpy, and excellent detonation performance have received increasing research attention. The conventional method of chemical dehydrogenation that is used to form azo compounds involves the use of strong oxidants, resulting in environmental pollution. Electrochemical organic synthesis is considered an old method and a new technology. In this work, azofurazan tetrazole {H₂AzFT; 5,5′-[diazene-1,2-diylbis(1,2,5-oxadiazole-4,3-diyl)]bis-1H-tetrazole} and azofurazan hydroxytetrazole (H₂AzFTO) were synthesized by a green and efficient electrochemical dehydrogenation coupling of 5-(4-aminofurazan-3-yl)-1H-tetrazole and 5-(4-aminofurazan-3-yl)-1-hydroxytetrazole, respectively. The structures of H₂AzFT and (NH₄)₂AzFTO were fully characterized by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis, and their thermal stabilities were determined by differential thermal analysis.

Over the past years our lab has established a research program towards the late-stage introduction of deuterium into organic molecules using Pd-catalyzed reversible C–H activation as a means to affect hydrogen isotope exchange. Through catalyst design, including the introduction of novel ligand scaffolds, as well as the use of strategically chosen optimization and screening approaches, e.g., exploiting microscopic reversibility by first optimizing de-deuteration processes or using a multi-substrate screening approach, our studies have resulted in a number of synthetically useful labelling protocols and are described herein from a personal perspective.

1 Introduction

2 β-C(sp³)–H Deuteration of Free Carboxylic Acids

3 Nondirected C–H Deuteration of Arenes

4 Nondirected C–H Deuteration of Heteroarenes

5 Conclusion

The electrophilic thiolation of alkenes initiated by DMTSM and the addition of CF₃SO₂Na in one pot has been developed. This reaction also can be extended to ArSO₂Na. This protocol features a good substrate scope, simple procedures, and mild reaction conditions and affords the desired products in moderate yields without metal catalysts.

Herein, we report a simple and noninvasive experimental protocol in which a series of relative reaction rates may be obtained by way of single competition experiments. This approach permits a quantitative comparison of any given number of chiral catalysts relative to a ‘benchmarking’ chiral catalyst – a particularly useful tool since catalyst design and selection have remained largely dependent on chemical intuition. We apply this benchmarking approach towards an asymmetric N-heterocyclic carbene (NHC) catalyzed intramolecular Stetter reaction as a proof-of-concept study. In doing so, we demonstrate a rapid method to assess the complex interplay between catalyst reactivity and stereoelectronic effects – an analytical approach that has heretofore not been attempted for NHCs. To showcase the generality of this method, we apply it to an enantioselective Rh(I)-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and aryl alkynes for a series of chiral phosphoramidite ligands. The results described herein demonstrate that this inexpensive and easily adoptable protocol can reveal complex yet subtle steric and stereoelectronic effects of vastly different chiral catalyst structures, which can further aid with catalyst development and selection for a clearly defined application.

We developed a redox-neutral synthesis of isoindoloindolone via intramolecular arylation of 2-(1H-indole-1-carbonyl)benzoic acids. This protocol facilitates the formation of various substituted isoindoloindolones in yields ranging from 17% to 80%. Our mechanistic investigations indicate the pivotal role of NaI: the iodide anion promotes the formation of the desired isoindoloindolone, and the sodium cation suppresses the formation of acylated byproducts, thereby enabling the selective formation of isoindoloindolones in acceptable yields.

An attempted aryl selenium-catalyzed formation of cis-chlorohydrins from alkenes was unsuccessful but led to an electrochemical investigation for the trans-selective chloroformyloxylation of cyclic and acyclic alkenes in moderate to good yields. Interestingly, when 1,1-disubstituted alkenes were used, the corresponding vinyl chloride derivatives were obtained, and the application of 1-phenylcyclohex-1-ene led to the formation of an allyl chloride derivative.

Over the past two decades, bioorthogonal chemistry has profoundly impacted various chemistry-related fields, including chemical biology and drug delivery. This transformative progress stems from collaborative efforts involving chemists and biologists, underscoring the importance of interdisciplinary research. In this Account, we present the developments in bioorthogonal chemistry within our Institute for Molecules and Materials at Radboud University. The chemistry disclosed here spans from strained alkynes and alkenes to drug release and bioconjugation strategies, mirroring the extensive scope provided by bioorthogonal chemistry. By reflecting on the chemistry originating at Radboud University, this Account emphasizes that teamwork is essential for driving significant progress in bioorthogonal chemistry.

1 Introduction

2 Providing BCN as a Robust Bioorthogonal Tool for Chemical Biology and Beyond

3 Towards Readily Available Click-to-Release trans-Cyclooctenes

4 Giving Molecules Guidance

5 Next Generation of Bioconjugation Strategies: Dynamic Click Chemistry

6 Conclusions