Synthesis of stereoisomeric 1,3-dimethyl- and 1,2,5-trimethyl-4-acyl(benzoyl)-4-piperidinols

In order to synthesize stereoisometric 4-acyl(benzoyl)-1, 3-dimethyl and-1, 2, 5-trimethyl-4-piperidinols, the reaction of the geometrical isomers of 4-cyano-1, 3-dimethyl- and -1, 2, 5-trimethyl-4-piperidinols and the amines and imidic esters corresponding to them with some alkyl- and arylmagnesium halides, leading to the corresponding isomeric piperidinic -ketols, has been studied. The dependence of the reactivity of the geometrical isomers of the compounds studied on the spatial orientation of their functional groups has been shown.     

Synthesis and three-dimensional structures of geometrical isomers of some 4-substitute d 1,2,5-trimethyl-4-acetoxy- and 1,2,5-trimethyl-4-benzoxypiperidines

Stereoisomers of the corresponding 4-substituted 1,2,5-trimethyl-4-acetoxy- and 1,2,5-trimethyl-4-benzoxypiperidines were obtained by acylation of the geometrical isomers of 1,2, 5-trimethyl-4-piperidol and its 4-ethynyl, 4-ethyl, and 4-phenyl-substituted derivatives. The preferred conformations of the investigated esters were elucidated by means of the PMR and IR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.1, pp. 50–55, January, 1973.     

Synthesis of 4-hydroxy-1,2,5-trimethyl-4-piperidyl carbinols

Spatial directivity of reactions of the geometrical isomers of 4-acetyl-, 4-propionyl-, and 4-benzoyl-1,2,5-trimethyl-4-piperidols with Grignard reagents and lithium aluminum hydride has been studied. Stereospecific synthesis of some stereoisomeric 4-hydroxy-1,2,5-trimethyl-4-piperidyl carbinols has been effected and their probable spatial configurations have been discussed.     

Synthesis and three-dimensional structure of the benzoates and p-nitrobenzoates of the geometrical isomers of substituted 4-hydroxypiperidines

The corresponding stereoisomeric p-nitrobenzoates were obtained by reaction of the geometrical isomers of 1,3-dimethyl-, 1,2,5-trimethyl-, and 1-tert-butyl-3-methyl-4-hydroxypiperidines with p-nitrobenzoyl chloride. The stereoisomers of the corresponding benzoates were also synthesized from the geometrical isomers of 1,3-dimethyl-4-hydroxypiperidines. The primary conformations of the investigated compounds in solution were established by means of their PMR spectra.     

New stereoselective syntheses of cis- and trans-2-methyl-4-arylpiperidines

A stereoselective approach has been developed for the synthesis of cis- and trans-2-methyl-4-arylpiperidines from a common intermediate. The Ni-catalyzed hydrogenolysis of N-Boc-2-methyl-4-aryl-4-piperidinols, obtained by addition of organometallic reagents on N-Boc-2-methyl-4-piperidone, afforded the trans derivatives with up to 95% selectivity whereas the corresponding cis isomers were obtained in the presence of palladium catalysts.     

Stereochemistry of hydroboration of 3(or 5)-methyl-4-phenyl-1,2,5,6-tetrahydropyridines

Hydroboration of N-substituted 5 - methyl - 4 - phenyl - 1,2,5,6 - tetrahydropyridines gave, as a sole product, the 5-methyl-4-phenyl-3-piperidinols, while the 3 - methyl - 4 - phenyl - 1,2,5,6 - tetrahydropyridines gave the 3-methyl-4-phenyl-3-piperidinols together with the 4-boryl-3-methyl-4-phenylpiperidine amine boranes. Structural and configurational assignments were made through the analysis of spectral data (IR, ¹H NMR and MS).     

Reaction of Zinc Enolates of Alkyl Esters of Substituted 4-Bromo-3-Oxoalkanoic Acids with Aldehydes

Zinc enolates formed from ethyl 4-bromo-2,2,4-trimethyl-3-oxopentanoate react under the conditions of one- of two-stage synthesis with aliphatic, unsaturated, or aromatic aldehydes to form 6-R-2,2,4,4-tetramethyl-2,3,5,6-tetrahydropyran-2,4-diones. Zinc enolates obtained from ethyl 4-bromo-2,2-dimethyl-3-oxopentanoate, -hexanoate, and -2,2,5-trimethyl-3-oxohexanoate under the similar conditions react with aliphatic or aromatic aldehydes to give mainly 5-R¹-6-R²-3,3-dimethyl-2,3,5,6-tetrahydropyran-2,4-diones as E or Z isomers or their mixtures. Zinc enolates generated from the ethyl 4-bromo-2,2-diethyl- or 2-benzyl-2-ethyl-3-oxobutanoates react with aromatic aldehydes to give ethyl 5-R-2-R-2-ethyl-3-oxo-4-pentenoates as E isomers.     

Alkylation of 4-oxo-3-methyl-4,5,6,7-tetrahydroindazoles

The alkylation of 4-oxo-3,6,6-trimethyl-4,5,6,7-tetrahydroindazole with alkyl halides forms mixtures of 1-alkyl and 2-alkyl derivatives which have been separated by fractional crystallization from n-hexane. The 4-oxo-1-alkyl-,-1-aryl-, and -1-acyl-4,5,6,7-tetrahydroindazoles have characteristic frequencies in their IR spectra at 1540-1530 cm^–1, and the corresponding 2-substituted derivatives have frequencies at 1565-1555 cm^–1. The introduction of an alkyl substituent at a nitrogen atom decreases the basicity of 4,5,6,7-tetrahydroindazole by 0.6 orders of magnitude, the 1-alkyl isomers being somewhat stronger bases than the 2-alkyl isomers.     

Studies of the elimination of 4-aryl-3-methyl-4-piperidinols—I The conformation of epimeric 1-alkyl (and aralkyl)-4-aryl-5-methyl-1,2,5-6-tetrahydropyridine hydrochlorides

A detailed study of the products of elimination of some 4-aryl-3-methyl-4-piperidinols has been made and the PMR spectra of derived 1-alkyl (and aralkyl)-4-aryl-5-methyl-1,2,5,6-tetrahydropyridines and the corresponding hydrochloric salts reported and discussed. The 5-methyltetrahydropyridine hydrochlorides are shown to exist in epimeric forms in deuterochloroform and their PMR spectra have been interperted in terms of probable conformations.     

Stereoselective additions to the exocyclic CC bond of some α-alkylidene-(+)-camphor derivatives

Stereoselective additions to the exocyclic CC double bond of some (1R,3E,4S)-3-alkylidene-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4E,5S)-4-alkylidene-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones were studied. All additions took place predominantly from the less hindered endo-face of the methylidene compounds to give the corresponding exo-adducts as the major isomers. Thus, catalytic hydrogenations afforded the α-alkylated (1R,3R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4R,5R)-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones in 28–100% de. Similarly, 1,3-dipolar cycloadditions of 2,4,6-trisubstituted benzonitrile oxides gave the corresponding spiro cycloadducts in 66–100% de. The structures were determined by 2D NMR techniques, NOESY spectroscopy and X–ray diffraction.     

Reactions of Sodium Enolates Derived from 6-Aryl-3,5,5-trimethyl-2,3,5,6-tetrahydropyrane-2,4-diones with Substituted Benzenesulfonyl Chlorides and Arenediazonium Salts

Sodium enolates derived from 6-aryl-3,5,5-trimethyl-2,3,5,6-tetrahydropyrane-2,4-diones react with substituted benzenesulfonyl chlorides to give the corresponding O-sulfonation products, 6-aryl-4-(4-R-phenylsulfonyloxy)-3,5,5-trimethyl-5,6-dihydropyrane-2-ones. Reactions of the title compounds with arenediazonium tetrafluoroborates afford 6-aryl-3-arylazo-3,5,5-trimethyl-2,3,5,6-tetrahydropyran-2,4-diones as mixtures of syn and anti isomers.     

New isomeric N-substituted hydrazones of 2-, 3-and 4-pyridinecarboxaldehydes

Eighteen compounds unknown in the literature, N-(E)-stilbenyloxyalkylcarbonyl- and N-(E)-stilbenyloxyalkylcarbonylaminoalkylcarbonyl-substituted hydrazones of 2-, 3- and 4-pyridinecarboxaldehydes have been prepared. The stereochemical behavior of these compounds in dimethyl-d₆ sulfoxide solution has been studied by ¹H-nmr technique. The E geometrical isomers and cisltrans amide conformers have been found for N-substituted-hydrazones 1–16 .     

Peculiarities of the three-dimensional structures of isomers of 1,2,5-trimethyl-4-amino(amido)piperidines from the 1H and 13C NMR spectra

The three-dimensional structures of seven 1,2,5-trimethyl-4-amino(amido)piperidines were studied by means of the ¹H and ¹³C NMR spectra. The ³J_HH values and the ¹³C chemical shifts indicate that the substituents in the piperidine ring of all of the 2c,5c,4r isomers have a 2e,4e,5a orientation, while those in the piperidine ring of all of the 2c,5t,4r isomers have a 2e,4e,5e orientation. The conformational change (as a result of ring conversion) 2e,4a,5e 2a,4e,5a was observed for the 2t,5c,4r isomers on passing from the corresponding amine to the amide; this change is associated with striving of the more bulky amide substituent to become equatorially oriented. Retarded rotation about the C₍₄₎-N bond was observed in the 2c,5t,4r isomer of the 4-(N-phenylbenzamido) derivative; this is explained by steric hindrance due to the 5e-CH₃ group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 54–57, January, 1988.The authors thank I. I. Chervin for assistance in recording the NMR spectra with a WM-400 spectrometer.     

1,2,5-Trimethyl-4-allyl(propargyl)-4-aryl(hetaryl)aminopiperidines

Individual geometrical isomers of some 1,2,5-trimethyl-4-allyl-4-aryl(hetaryl)aminopiperidines were isolated, and their structures were established. 1,2,5-Trimethyl-4-propargyl-4-aryl(aralkyl)aminopiperidines were obtained from 1,2,5-trimethyl-4-aryliminopiperidines and propargylmagnesium bromide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 942–946, July, 1991.     

Cyanoethylation of some n-substituted 2,5-dimethyl-4-piperidones

1,2,5-Trimetnyl- and 1-(-chlorocrotyl)-2,5-dimethyl-5-(-cyanoethyl)-4-piperidones were synthesized and separated into individual isomers. The corresponding isomeric 5-(-carboxyethyl)-4-piperidones were obtained by hydrolysis. The isomeric 1,2,5-trimethyl-3,5-bis(-cyanoethyl)- and 1,2,5-trimethyl-3,3,5-tris(-cyanoethyl)-4-piperidones were synthesized by subsequent cyanoethylation of the individual 1,2,5-trimethyl-5-(-cyanoethyl)-4-piperidone isomers.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 479–481, April, 1971.     

Asymmetric synthesis,stereochemistry, and absolute configuration of 1,2-5-trimethyl-5-(2-cyanoethyl)- and 1,2,5-trimethyl-4-piperidinones

The asymmetric Michael alkylation of (–)-1,2,5-trimethyl-4-(1S-phenylethylimino)piperidine by electrondeficient alkenes proceeds with the formation of(+)-cis-(2S,5S)- and (–)-trans-(2R,5S) diastereomers of 1,2,5-trimethyl-5-(2-cyanoethyl)- and 1,2,5-trimethyl-5-(2-methoxycarbonylethyl)-4-piperidinones containing a chiral quaternary center C(₅). The spatial structure of these new chiral 4-piperidinones has been established on the basis of ¹H and ¹³C NMR spectroscopic data. The absolute configuration of the C(₂) and c(₅) chiral centers in the diastereomers has been determined by stereochemical correlation on the basis of circular dichroism data.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1369–1378, October, 1992.     

Synthesis of siloxanes : XXII. Synthesis and crystal structure of 2-t-butoxy-2,4,6-trimethyl-4,6-diphenyl-(2α,4α 6α)-cyclotrisiloxane

The structure of 2-t-butoxy-2,4,6-trimethyl-4,6-diphenyl-(2α,4α,6α)-cyclotrisiloxane has been determined by an X-ray crystallographic study. The structure revealed confirms the validity of the basis of our ²⁹Si and ¹H NMR assignments previously made to configurational isomers of several model compounds, which are suitable for studying the stereochemistry of substitutions at silicon atoms in siloxanes     

1,4-bis(4′-hydroxy-1′,2′,5′-trimethyl-4-piperidyl)-1,3-butadiyne and its derivatives

1.4-Bis(4-hydroxy-1,2,5-trimethyl-4-piperidyl)-1.3-butadiyne has been synthesized from the individual isomers of 4-ethynyl-1,2,5-trimethyl-4-piperidol. Hydrogenation, bromination, and cleavage have given, respectively, 1,4-bis(4-hydroxy-1,2,5-trimethyl-4-piperidyl)butane, 1,4-bis(4-nydroxy-1,2,5-trimethyl-4-piperidyl)-1,2,3,4-tetrabromo-1, 3-butadiene, and 4-(1,3-butadiynyl)-1,2,5-trimethyl-4-piperidol.     

Stereochemistry of diastereoisomeric propionyl esters of 4-(2-furyl)-3-methyl-1-phenethyl-piperidin-4-ols and the analgesic ether derived from their acid-catalysed ethanolysis

The stereochemistry of diastereoisomeric propionyl esters of 4-(2-furyl)-3-methyl-1-phenethylpiperidin-4-ols has been established by ¹³C NMR analysis. Both isomers, after acid-catalysed ethanolysis, are converted to the corresponding 4-ethoxy derivative of configuration (t-3-Me, r-4-OEt) that correlates with its analgesic properties.     

Synthesis of (5R*)- and (5S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-ones

Heating of N-benzoyl-N-[2-(1-methylbut-2-en-1-yl)-4-methylphenyl]glycine with ethyl chloroformate or acetic anhydride gave (5R*) and (5S*) isomers of (1R*,3aS*,4S*,11S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one.