Synthetic applications of N–N linked heterocycles. Part 11. Regiospecific synthesis of dialkyl pyridin-4-yl-, quinolin-4-yl-, and isoquinolin-1-yl-phosphonates

Katritzky, Alan R.; Keay, James G.; Sammes, M. P.

doi:10.1039/p19810000668

Cited by 17 publications

(14 citation statements)

References 3 publications

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“…This reaction is advantageous because the previous methods 80,81 82 Very recently, McNally and co-workers reported a new approach for the two-step C4-functionalization of pyridine (Figure 6). 83 Heterocyclic phosphonium salts, which can be prepared via reactions of azines with triphenylphosphine in the presence of trifluoromethanesulfonic anhydride, 84,85 undergo S N Ar reactions with various nucleophiles such as alkoxides, thiolates, azides, or organolithium reagents. The reaction of C4substituted azines proceeds at the C2-position.…”

Section: Introductionmentioning

confidence: 99%

C–H Functionalization of Azines

et al. 2017

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Azines, which are six-membered aromatic compounds containing one or more nitrogen atoms, serve as ubiquitous structural cores of aromatic species with important applications in biological and materials sciences. Among a variety of synthetic approaches toward azines, C-H functionalization represents the most rapid and atom-economical transformation, and it is advantageous for the late-stage functionalization of azine-containing functional molecules. Since azines have several C-H bonds with different reactivities, the development of new reactions that allow for the functionalization of azines in a regioselective fashion has comprised a central issue. This review describes recent advances in the C-H functionalization of azines categorized as follows: (1) SAr reactions, (2) radical reactions, (3) deprotonation/functionalization, and (4) metal-catalyzed reactions.

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Section: Introductionmentioning

confidence: 99%

C–H Functionalization of Azines

et al. 2017

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“…For example, exclusive C4 attack requires bulky substituents at the C2 and C6 positions. [7][8][9] Redmore reported methods, which were very useful in the case of C2 substitution, but needed 2,6-dialkyl-substituted N-alkoxypyridinium or N-tritylpyridinium salts to protect both the C2 and C6 positions in order to synthesize the 4-isomer, using sodium phosphonates as nucleophiles. 8, 10 Akiba synthesized the pure diisopropyl 1-(ethoxycarbonyl)-1,4-dihydropyridine-4-phosphonate, 7 while in the case of other phosphites, unpredictable molar ratios of isomeric C2/C4 dihydropyridines were also observed.…”

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confidence: 99%

Synthesis of PO(OR)2- and PR3+-Disubstituted Pyridines via N-(Trifluoromethylsulfonyl)pyridinium Triflates

Haase¹,

Goerls²,

Anders³

1998

Synthesis

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The efficient synthesis of dialkoxyphosphoryl-and phosphonio-substituted pyridines is reported. The cationic heterocycle of N-(trifluoromethylsulfonyl)pyridinium triflate (3), or of analogous N-(trifluoromethylsulfonyl) compounds prepared from pyridine-4phosphonium salts 5, turns out to be sufficiently activated to allow attack of P(OR) 3 and PR 3 + nucleophiles to give the novel compounds bis(dialkoxyphosphoryl)pyridines 11 and phosphonio(dialkoxyphosphoryl)pyridines 13. For example, 13a-d, with PO(OR) 2 at the C2 and PR 3 + at the C4 position, represent the first examples of an Nheteroaromatic ring substituted by both dialkoxyphosphoryl and phosphonio moieties. The structure of 13b [PPh 3 + /PO(O-i-Pr) 2 ] was confirmed by X-ray analysis. In most cases, the intermediate 1-(trifluoromethylsulfonyl)dihydropyridines, such as 7, 8 (monosubstituted) or 10a and b and 12a-d (disubstituted), are sufficiently stable for isolation.

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“…In contrast to related dihydropyridines, 3 it is more convenient to separate the dihydroquinolines 9 and 10 by simple column chromatography. Both dihydro isomers could be successfully deprotonated with Et 3 N either in the crude reaction mixture or after column chromatography to obtain 11 1 and 12 1 , 5 . This behavior contrasts with that of related pyridine systems, 3 in which only the 1,4-dihydro compounds could be deprotonated.…”

Section: Methodsmentioning

confidence: 99%

“…We have mentioned that it was necessary to use a stronger base than Et 3 N for the deprotonation of compound 13. When BuLi was used, 1-butylisoquinoline (26a) was obtained in 16% yield 14 in addition to the expected product 14 1,5,15 (49%) and the starting compound 13 (35%). The formation of the isoquinoline 26a is due to the competition between hydrogen abstraction and nucleophilic substitution of the phosphonato group with BuLi.…”

Section: Methodsmentioning

confidence: 99%

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N-Heteroarylphosphonates, Part II. Synthesis and Reactions of 2- and 4-Phosphonatoquinolines and Related Compounds

Haase¹,

Günther²,

Görls³

et al. 1999

Synthesis

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We extend our synthetic method for the efficient preparation of dialkoxyphosphoryl-and phosphonio-disubstituted pyridines to include the preparation of other phosphonato substituted N-heterocycles. The key to the success of this method lies in the employment of cationic N-(trifluoromethylsulfonyl)heteroarylium triflates that are activated towards nucleophilic attack. The P(O)(OR) 2 group can be transformed into the P(S)(OR) 2 functionality. We report first attempts to substitute the P(O)(OR) 2 moiety with C-nucleophiles. In addition to our synthetic results, the X-ray structures of two (dimethoxyphosphoryl)trifluoromethanesulfonyldihydro-Nheteroarenes are discussed. We also give complete carbon ( 13 C) and phosphorus ( 31 P)-NMR spectra of a series of 2-and 4-phosphonic ester substituted heteroaryl compounds and their dihydro analogs.Heterocyclic compounds containing P(O)(OR) 2 functionalities in which the phosphorus group is ortho or para to the nitrogen in the heterocycle deserve interest as they have been used to inhibit the corrosion of ferrous metals and can be employed as passive coating agents by dissolving them in the corrosive medium. Examples are brines, weak inorganic acids, CO 2 , H 2 S, etc. These compounds and their derivatives are also employed as additives for sludging and cutting oils, as wetting, rewetting, dispersing and as antistatic agents in the textile and polymer industry. Further useful applications are as emulsifiers for insecticides and agricultural chemical mixtures. 1 In contrast to the corresponding non-quaternized compounds, which show no microbiocidal activity, the quaternized compounds are active as biocides or biostats. These compounds are employed in many areas of industrial chemistry such as bactericides, herbicides, chelating agents, etc. 2 We reported in a recent article 3 that the conclusions drawn from our new synthetic procedure for the preparation of dialkoxyphosphoryl substituted pyridines via N-(trifluoromethylsulfonyl)pyridinium triflates and the appropriate dihydropyridines lead away from the exclusive use of pyridine itself. This procedure profits from the quantitative in situ formation of N-(trifluoromethylsulfonyl)pyridinium triflate, which reacts with P(OR) 3 . 4 The addition of Et 3 N to the reaction mixture transforms the intermediate N-trifluoromethanesulfonyldihydropyridines in to the corresponding 4-phosphonato substituted pyridines. The easy removal of the N-triflyl group then allows the straightforward repetition of this procedure, which finally yields 2,4-bis(dialkoxyphosphoryl)pyridines.In the present article, we report on investigations which tested the influence of steric hindrance (Scheme 1) on the success of our method by employing 3,5-diphenylpyridine (1) and 2,6-diphenylpyridine (5). The di-meta substituted compound 1 reacted as expected to form compound 3, which could be rearomatized to 4 by deprotonation with BuLi. However, the di-ortho substituted compound 5 did not react with Tf-O-Tf 2. Since the electronic properties of the nitrogen atom can...

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Synthetic applications of N–N linked heterocycles. Part 11. Regiospecific synthesis of dialkyl pyridin-4-yl-, quinolin-4-yl-, and isoquinolin-1-yl-phosphonates

Cited by 17 publications

References 3 publications

C–H Functionalization of Azines

C–H Functionalization of Azines

Synthesis of PO(OR)2- and PR3+-Disubstituted Pyridines via N-(Trifluoromethylsulfonyl)pyridinium Triflates

N-Heteroarylphosphonates, Part II. Synthesis and Reactions of 2- and 4-Phosphonatoquinolines and Related Compounds

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