Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro-2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

Parks, Emma L.; Sandford, Graham; Christopher, John; Miller, David D.

doi:10.3762/bjoc.4.22

Cited by 9 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described in our previous report, we synthesized a novel P-heteroarylated 1,3-diphosphacyclobutane-2,4-diyl via the S N Ar reaction of the 1,3-diphosphacyclobuten-4-yl anion. Reaction of phosphaalkyne 1 , , 0.5 equiv of t -butyllithium, and 5-chloro-2,4,6-trifluoropyrimidine afforded the pyrimidine-substituted 3 in 80% isolated yield via regioselective activation of the C–F bond by 2 (Scheme ). The calculated highest occupied molecular orbital (HOMO) of 2 , optimized at the CAM-B3LYP/6-31+G(d) level (Figure ), indicated that P–C bond formation is not regulated by orbital control.…”

Section: Resultsmentioning

confidence: 99%

Chemical Detection of Hydrogen Fluoride by the Phosphorus Congener of Cyclobutane-1,3-diyl

2015

View full text Add to dashboard Cite

Heteroaryl-substituted air-tolerant 2,4-bis(2,4,6-tri-t-butylphenyl)-1,3-diphosphacyclobutane-2,4-diyls in the open-shell singlet state were synthesized by a sterically promoted regioselective S(N)Ar process. Here we demonstrate that these diyls are effective for capturing hydrogen fluoride (HF) generated by intermediary base-coordinated HF and amine-stabilized HF reagents. The hydrofluorination reaction predominantly occurred on the λ(3)σ(3)-phosphorus atoms to afford the energetically disfavored 1λ(5),3λ(5)-diphosphete. The positively charged t-butyl-substituted phosphorus atom trapped the fluoride anion, and the subsequent protonation was controlled by the steric effect. X-ray crystallographic analysis and an Atoms in Molecule study of the air-stable 1λ(5),3λ(5)-diphosphete bearing P-H and P-F bonds revealed that the delocalized ylidic linkages in the four-membered ring were almost identical, in contrast to the nonsymmetrically substituted 2,4-bis(2,4,6-tri-t-butylphenyl)-1,3-diphosphacyclobutane-2,4-diyl. Hydrofluorination efficiently induced a remarkable exchange of visible photoabsorption. The charge-transfer-type transition from highest occupied molecular orbital to lowest unoccupied molecular orbital was highly tuned, which is advantageous for the facile identification of HF. In contrast to hitherto known trapping reagents for HF based on cleavage of the H-F bond, several hydrofluorinated P-heterocycles were reconverted into the 1,3-diphosphacyclobutane-2,4-diyl by treatment with sodium hydride. However, in the hydrofluorination of the benzoyl-substituted 1,3-diphosphacyclobutane-2,4-diyl, fluorination and protonation occurred at the t-butyl-substituted phosphorus atom and the skeletal carbon atom, respectively, and the energetically preferable 1λ(5),3λ(3)-dihydrodiphosphete was isolated as a purple-blue crystalline compound. These findings are promising not only for the practical detection of HF but also for the development of fluorine technology based on the chemistry of phosphorus heterocycles.

show abstract

Section: Resultsmentioning

confidence: 99%

Chemical Detection of Hydrogen Fluoride by the Phosphorus Congener of Cyclobutane-1,3-diyl

2015

View full text Add to dashboard Cite

show abstract

“…Large number of synthetic methods have been described for the preparation of pyrimidine-based compounds [11][12][13][14][15][16]. Cyclocondensation between guanidine, amidine or thiourea derivatives and 1,3-diketones or 1,3-diesters is the most classical method for the synthesis of the main pyrimidine core [15,17], whereas one of the approaches to prepare substituted pyrimidine rings is via halogenated pyrimidines [18][19][20], which are greatly commercially available. The most common reactions involving various halogenated pyrimidines are cross-coupling reactions since pyrimidine ring is an electron-deficient aromatic system being far more reactive in comparison with analogous benzene halides [17,20].…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Regioselective Suzuki Coupling of 2,4-Dichloropyrimidines with Aryl and Heteroaryl Boronic Acids

2021

View full text Add to dashboard Cite

Suzuki coupling reaction has been often used for the preparation of a diverse set of substituted pyrimidines. In this study, the Suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation led to a very efficient and straightforward synthetic procedure providing C4-substituted pyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) are the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of substituted pyrimidine rings.

show abstract

“…Aromatic nucleophilic substitution in per-and poly-fluorinated arenes 1,2 is a valuable method for constructing highly functionalised heterocycles and aromatics. 3 Such compounds have been widely investigated by Chambers 4 and Sandford 5 and have been used as scaffolds for drug discovery. 6 The mechanistic and synthetic potential of fluorinated arenes has been reviewed.…”

mentioning

confidence: 99%

Synthesis of fluorinated fused benzofurans and benzothiophenes: Smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides

et al. 2011

View full text Add to dashboard Cite

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro-2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

Abstract: Background

Cited by 9 publications

References 16 publications

Chemical Detection of Hydrogen Fluoride by the Phosphorus Congener of Cyclobutane-1,3-diyl

Chemical Detection of Hydrogen Fluoride by the Phosphorus Congener of Cyclobutane-1,3-diyl

Microwave-Assisted Regioselective Suzuki Coupling of 2,4-Dichloropyrimidines with Aryl and Heteroaryl Boronic Acids

Synthesis of fluorinated fused benzofurans and benzothiophenes: Smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides

Contact Info

Product

Resources

About