Pyrimidin‐6‐yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis

Cousins, David L.; Fricero, Prisca; Kopf, Kenji P. M.; McColl, Elliot J.; Czechtizky, Werngard; Lim, Yee Hwee; Harrity, Joseph P. A.

doi:10.1002/anie.202101297

Cited by 7 publications

(2 citation statements)

References 27 publications

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“…We envisage that the introduction of boron substituents at β position will enable us to tune the chemoselectivity and stability, preventing retro processes via coordination of the carbonyl group with the boron moiety ( 46 ), thereby overcoming the limitations of the existing methods. Previously, β-boryl alkynyl ketones were applied in the heterocycle synthesis such as pyrazoles ( 47 ) and pyrimidines ( 48 ) from hydrazine and amidines, respectively. So far, no precedent has been reported in the direct conjugate addition of simple amines or amino biomolecules to alkynyl carbonyl β-borates, especially in water or under biocompatible conditions.…”

Section: Introductionmentioning

confidence: 99%

Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents

Teng

Zhang

et al. 2023

Sci. Adv.

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Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods reported thus far. Here, we report an amine-specific click reagent using alkynone β-trifluoroborates as the electrophiles. These boron-containing alkynyl reagents exhibit extremely high chemoselectivity toward amines even in the presence of thiols. The resulting oxaboracycle products are bench-stable, displaying the reactivities of both organoborates and enaminones. Intrinsic advantages of this methodology include benign reaction conditions, operational simplicity, remarkable product stability, and excellent chemoselectivity, which satisfy the criteria of click chemistry and demonstrate the high potential in bioconjugation. Hence, this water-based chemical approach is also applicable to the modification of native amino acids, peptides, and proteins. Ultimately, the essential role of water during the reaction was elucidated.

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Section: Introductionmentioning

confidence: 99%

Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents

Teng

Zhang

et al. 2023

Sci. Adv.

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“…These compounds were isolated as single regioisomers and the regioselectivity was assigned by X-ray crystallography and HMBC spectroscopy (see Supporting Information). [16] Turning to the trifluoroborate, we were pleased to find that this group proved to be amenable to promoting cross-coupling with aryl iodides, furnishing biaryl products 11 a,b in good yield. Finally, subjecting 4 a to bromination results in clean electrophilic aromatic substitution at the pyrimidine C5 position, leaving the trifluoroborate group intact.…”

mentioning

confidence: 99%

Pyrimidin‐6‐yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis

et al. 2021

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We report a novel and general method to access a highly under‐studied privileged scaffold—pyrimidines bearing a trifluoroborate at C4, and highlight the broad utility of these intermediates in a rich array of downstream functionalization reactions. This chemistry is underpinned by the unique features of the trifluoroborate group; its robustness provides an opportunity to carry out chemoselective reactions at other positions on the pyrimidine while providing a pathway for elaboration at the C−B bond when suitably activated.

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Tandem [3+1+1+1] Heterocyclization of α‐Acyl Ketene Dithioacetals with Ammonia and Methanol: Rapid Assembly of Polysubstituted Pyrimidines

Wang

Zhang

et al. 2022

Eur J Org Chem

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A straightforward copper‐catalyzed aerobic cyclocondensation reaction of α‐acyl ketene dithioacetals with ammonium acetate and methanol was developed for synthesizing highly functionalized pyrimidines. This domino conversion relied on the dual activities of CuCl2, namely Lewis acid and dehydrogenation, which began with single C−S ammonolysis directed by an in situ generated imine, followed by cyclocondensation with aldehyde produced from alcohol and concomitant oxidative dehydrogenation under an oxygen atmosphere. Notably, readily accessible and flexible substrates, common chemical feedstock nitrogen and C1 sources, good functional group tolerance and procedural simplicity exhibit the efficiency and potential application of the new method.

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Pyrimidin‐6‐yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis

Cited by 7 publications

References 27 publications

Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents

Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents

Pyrimidin‐6‐yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis

Tandem [3+1+1+1] Heterocyclization of α‐Acyl Ketene Dithioacetals with Ammonia and Methanol: Rapid Assembly of Polysubstituted Pyrimidines

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