Isoquinolines phosphonates

The reaction of nitronaphthalenes and nitroisoquinolines with dimethyl phosphite in MeONa/MeOH (equation 27), proceeded via nucleophilic substitution of hydrogen according to a redox stoichiometry and gave substituted dimethyl naphthalene- and isoquinoline-phosphonates and benzazepines.214... 

Benzo derivatives of the pyrido[l,2-f][l,3,2]oxazaphosphorine ring system, [l,3,2]oxazaphosphorino[4,3- ]isoquino-lines 195, 196, were synthesized by the reaction of hydroxyethyl isoquinoline derivatives 183, 184 with phenylphos-phonic dichloride, bis(2-chloroethyl)phosphonic dichloride or phosphoryl chloride. In almost all cases, the products were formed in about a 1 1 diastereomeric ratio. The only exception observed was when phosphoryl chloride was used as the reagent (X = C1) in this reaction one single diastereomer 196 (R2 = R3 = H) was obtained (Scheme 28) <2000JST(554) 119, 2000JOC316>. 

Katritzky, A.R., Zhang, G., and Jiang, J., Convenient preparations of diethyl [(acylamino)methyl]phosphonates, 2-azabutadienes, and isoquinolines from a 1,2-monoazabisylide equivalent,. Org. Chem., 59, 4556, 1994. 

Katritzky, A.R., Keay, J.G., and Sammes, M.P., Regiospecific synthesis of dialkyl pyridin-4-yl, quinolin-4-yl, and isoquinolin-l-yl-phosphonates, /. Chem. 

Phosphonate analogues of Reissert compounds (76) have been prepared and converted into 1-alkyl-isoquinolines (Scheme 49). Treatment of a number of A -methylisocarbostyrils with mercuric acetate gave rise to 4-mercuri-ated derivatives, which underwent insertion reactions with methyl acrylate and with styrenes in the presence of palladium chloride (Heck reaction). 

Scheme 68 Copper-catalyzed cross-coupling of an H-phosphonate and an isoquinoline...

A more unusual leaving group (H) was employed in copper-catalyzed aerobic phosphonation of sp C-H bonds in an isoquinoline derivative (Scheme 68). A speculative mechanism involving nucleophilic attack on a Cu-complexed imine was proposed [121]. 

The 1 -alkyl substituted isoquinolines have been modified via the reaction between imines and ethyl chloroformate followed by trimethyl phosphite to form carbamate phosphonate intermediates that cyclize into isoquinolines in the presence of Lewis acid. ... 

The data on the Sn reactions of phosphorus-centered nucleophiles with electro-phihc nitroarenes and azines are scarcely available in the literature [11, 159] Although a number of o -adducts derived from the addition of P-nucleophiles to isoquinoline [140], phthalazine [160], 4,7-phenanthroline [161, 162], A -alkyl-pyrazinium, and quinoxalinium salts [163] have been isolated and identified by NMR and X-ray crystallography, no attempts to convert these o -adducts into the corresponding Sn products have been done. For instance, Af-ethylpyrazinium tetrafluoroborate reacts with dialkyl and diaryl phosphonates under very mild conditicHis (room temperature, acetonitrile) to give stable dialkyl 3-phenyl-5,6-dicyano-l-ethyl-l,2-dihydropyrazin-2-yl phosphonates in good yields (Scheme 50) [163],... 

Unequivocal evidence for the formation of o -adducts has been obtained by X-ray diffraction analysis of those adducts which are stable enough to obtain their single crystals [11]. Indeed, the X-ray crystallography data are available for the anionic trinitrobenzene-methoxide and the Janovsky trinitrobenzene-acetone complexes [11, 201, 202] and for the o -adducts of isoquinoline [203], phthalazine [160], and 4,7-phenanthroline [161, 162] with dialkyl phosphonates. Also the X-ray data have been obtained for the neutral o -adducts resulting from the reactions of iV-methylacridinium ion with N-nucleophiles [204, 205] and for the o -adducts of iV-alkyl-substituted 2,3-dicyanopyrazinium and quinoxalinium salts with 0-, C-and P-nucleophiles [163, 194]. 

The quaternary ammonium urethanes produced by iV-acylation of pyridines " and isoquinolines " with chloroformates react with trialkylphos-phites to give the phosphonates (153) and (154), respectively. Wittig-Homer reaction with aldehydes and subsequent re-aromatization then gives the corresponding alkylated heterocycles. 

A noyel approach to 1-phosphoiylated isoquinolines (373) has been realised through a silyer(i)-catalysed tandem reaction of 2-allqmylbenzaldoxime (372) with dialltyl phosphites (ff-phosphonate) (Scheme 111). The reaction proceeded smoothly to construct C-N and C-P bonds in one-pot with good functional group tolerance under mild conditions. ... 

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