Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

Synthesis of 1-(2-naphthyl)dihydro- and 1-(2-naphthyl)-2-thiodihydrouracils and their transformations

1-(2-Naphthyl)dihydro- and 1-(2-naphthyl)-2-thiodihydrouracils were obtained from N-(2-naphthyl)--alanine derivatives. The thiodihydrouracil was converted to a dihydrouracil. Bromination of 1-(2-naphthyl)dihydrouracil gave (1-bromonaphthyl)dihydrouracil. 1-(2-Naphthyl)-2-oxo-, 1-(2-naphthyl)-2-thio-. and 1-(1-bromo-2-naphthyl)-2-oxohexahydro-pyrimidines were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 12, pp. 1695–1697, December, 1971.     

1-benzoyl-2-(2-naphthyl)-selenourea

During our synthesis of N-benzoyl-N'-aryl selenourea derivatives, we isolated the title compound. One of them was selected optically for the diffraction study. The crystal belongs to the Monoclinic space group P21/n, Mr = 353.27, a = 11.073(1)A, b = 5.745(1) A, c = 24.356(5) A, β= 92.10 (1) °, V= 1548.3 (4) A3, Z = 4, Dx=1.515 Mg/m3, λ (Mo Kα )=0.71073 A, θ = 1.67-25, μ= 2.428 mm-1 , T = 296 (2) K.View of the molecule showing the labeling of the non-H atoms are described as:The selenourea and thiourea have analogous structure, a few literatures have reported the crystal of N-benzoyl-N'-aryl thiourea derivative1,2. In the reported crystal structure of N-benzoyl-N'-aryl thiourea derivative, there is a intermolecular hydrogen bond between the carbonyl O and H atom on N', in each -C(O)-NH-N'H- moiety, forming a planar six-membered ring. In this title compound,[2.654(2)A], C (8), N (1) and C (7)l.In the crystal structure of N-benzoy-N'-aryl thiourea derivative, there have a two dimensional With the intramolecular hydrogen bond [2.654(2)A] they form the planar four-membered ring between every molecular. The atom of Se dose not link the moleculars like the S atom of N-benzoyl-N'-aryl thiourea derivative, and it is only out of six-membered ring, which forms by N (2)H…O, C (8), N (1) and C (7).     

Stereoselective functionalization of 2-(1-aminoalkyl)aziridines via lithiation of aziridine-borane complexes

Highly selective functionalization of the aziridine ring of (2S,1'S)-2-(1'-aminoalkyl)aziridines 1, through successive formation of aziridine-borane complexes, lithiation, treatment with a variety of electrophiles and final decomplexation is described. The influence of the structure of the starting complexes 2 and of the electrophiles in the stereoselectivity of this process has been studied. Finally, successive double lithiation-electrophile reactions were carried out affording enantiopure 1,2,3,3-tetrasubstituted aziridine-borane complexes with high selectivity.     

Acetylation of 2-(1-naphthyl)thiophene

Acetylation of 2-(1-naphthyl) thiophene with acetyl chloride in the presence of SnCl₄, or with acetic anhydride in the presence of H₃PO₄ gives 5-aceto-2-(1-naphthyl) thiophene. 5-Ethyl-2-[1-(3, 4-dihydronaphthyl)] thiophene, 5-ethyl-2-(1-naphthyl) thiophene and 3, 4-diacetoxymercuri-5-ethyl-2-(1-naphthyl) thiophene are now synthesized and characterized.     

Pyrroles from ketoximes and acetylene. 23. 2-(1-naphthyl)- and 2-(2-naphthyl)pyrroles and their 1-vinyl derivatives

2-(1-Naphthyl)- and 2-(2-naphthyl)pyrroles and their 1-vinyl derivatives were synthesized in 22–64% yields by the reaction of 1- and 2-acetylnaphthalene oximes with acetylene at both atmospheric pressure and elevated pressures in an alkali metal hydroxide-dimethyl sulfoxide system.See [1] for communication 22.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1351–1353, October, 1982.     

Synthesis of 2-(1-alkoxyvinyl)pyridines

2-(1-Bromovinyl)pyridine, 2-ethynylpyridine, 2-(1-alkoxyvinyl)pyridines, and 2-(2-alkoxyvinyl)pyridines (the cis and trans isomers) were detected in the reaction mixture by mass spectrometry in the reaction of 2-vinylpyridine with bromine with subsequent dehydrobromination of the addition product with an alcohol solution of alkali. The conditions for the preparation of chromatographically pure compounds were found.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 647–650, May, 1978.     

Nitro derivatives of 2-(1-naphthyl) thiophene

2-[1-(3, 4-Dihydronaphythyl)]thiophene, 2-(1-naphthyl)thiophene, 3, 4, 5-triacetoxymercuri-, 3, 4-diacetoxymercuri-5-nitro-, 4, 5-diacetoxymercuri-3-nitro-2-(1-naphthyl)thiophenes and 3, 3, 4-triacetoxymercuri-2[1-(4-nitronaphthyl)]thiophene are synthesized and characterized. Nitration of 2-(1-naphthyl)thiophene with copper nitrate in acetic anhydride leads to formation of two isomeric mono-nitro derivatives, 4-nitro- and 5-nitro-2-(1-naphthyl)thiophene.     

3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.     

Functionalisation of 1,2,3-triazole via lithiation of 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazole

The preparation of a number of 5-substituted 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazoles via reaction of 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazole with n-butyllithium followed by addition of various electrophiles is reported. Removal of the protecting group by action of diluted aqueous hydrochloric acid or by tetrabutylammonium fluoride in tetrahydrofuran leads to the appropriate 4-substituted 1H-1,2,3-triazoles.     

Conformational analysis of methyl 2-methyl-2-(1-naphthyl)propionate

(S)-2-Methoxy-2-(1-naphthyl)propionic acid (MαNP acid 1) is used for enantioseparation of many secondary alcohols and for determining the stereogenic centers. In the liquid state, based on the ¹H NMR anisotropy effect and reported results, it was shown that the MαNP ester preferred a coplanar relation between the methyl and naphthyl groups and a synperiplanar relation between the Cα-OMe and CO groups. In the case of 1,2,3,4-tetrahydro-4-phenanthrenol, which is a secondary alcohol, the stereogenic center was determined by X-ray analysis. It was shown that MαNP ester adopted similar arrangements in the solid state. However, it was presumed that the strong repulsion between oxygen atoms may be disadvantageous in the solid state. Therefore, we carried out conformational analysis using the simplest MαNP methyl ester to clarify this unique relationship. From detailed results based on the energy surface determined using the RHF/STO-3G basis set, the synperiplanar positional relation was the most stable, and the calculated results agreed with many reported experimental results. At the same time, all conformational isomers of the MαNP methyl ester were used to clarify the internal conversion pathways.     

Analyses of in-cage singlet radical-pair motions from irradiations of 1-naphthyl (R)-1-phenylethyl ether and 1-naphthyl -2-phenylpropanoate in n-alkanes

[reaction: see text] The regio- and stereochemistries of photo-Claisen reactions of 1-naphthyl (R)-1-phenylethyl ether ((R)-2), in combination with photo-Fries and photo-Claisen-type reactions of 1-naphthyl (R)-2-phenylpropanoate ((R)-1), have been investigated in n-alkanes of different viscosities and at several temperatures. Analyses of the results provide detailed information about the in-cage motions of the singlet prochiral 1-naphthoxy/1-phenylethyl radical pairs (radical-pair B) that are formed directly from (R)-2 and indirectly from (R)-1 via decarbonylation of singlet chiral 1-naphthoxy/2-phenylpropanoyl radical pairs (radical-pair A). In hexane at 23 degrees C, the photo-Claisen products from irradiations of (R)-2 retain up to 31% enantiomeric excess (ee), but the ees of the same photoproducts from (R)-1 are near 0%. This disparity is attributed to differences between the initial orientations of the constituent radicals of radical-pair B at the moment of their "birth". The regio- and stereoselectivities reach plateau values as the solvent viscosity increases, indicating that the relationships between the rates of radical-radical bond formation and either translational or tumbling motions within a solvent cage reach an asymptotic limit. Detailed analyses are presented of the various motions that are in competition within a solvent cage during the very short lifetimes of the radical pairs. The data, in toto, present interesting insights into how radical pairs move during short periods and over short distances when their solvent cages have walls of varying flexibility.     

Synthesis and deprotonation of 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines

The ability of the 2-pyridyl and 1-isoquinolyl groups to direct metalation was studied in the benzene series. For this purpose, 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines were prepared. Interestingly, nucleophilic addition reactions on the azine ring were not observed under kinetic control using butyllithium, and the substrates were cleanly deprotonated on the benzene ring: the azine ring acidifies the adjacent hydrogen H2' (N-H2' interaction through space and/or inductive electron-withdrawing effect) and probably favors the approach of butyllithium (chelation). Under thermodynamic conditions using lithium dialkylamides, the presence of the azine group makes the lithio derivative at C2' more stable (chelation and/or inductive electron-withdrawing effect). This was evidenced in two ways: (1) syntheses of 2-halophenyllithiums (F, Cl, Br) substituted at C6 by a 2-pyridyl or 1-isoquinolyl group without elimination of lithium halide and (2) iodine migration from C2' to C4' when treating 2-(3-halo-2-iodophenyl)pyridines or 1-(3-fluoro-2-iodophenyl)isoquinoline with LTMP. Comparisons between the 2-pyridyl and fluoro units showed the latter was the stronger directing group for deprotonation.     

Nitrogen derivatives of 2-(1-naphthyl) thiopene. II

5-Amino-2-(1-naphthyl) thiophene and 4-amino-2-(1-naphthyl) thiophene are synthesized in the form of their complex salts with stannic chloride. It is shown that the stannic chloride complexes with amino derivatives of 2-(1-naphthyl) thiophene diazotize, and can be used as azo components.For Part I see [1].     

Regioselective synthesis of 2-substituted pyridines via grignard addition to 1-(alkoxycarboxy)-pyridinium salts

A regioselective one pot synthesis of 2-substituted pyridine derivatives from pyridine-1-oxides is described.