Irina Soloshonok

Chiral sulfoxide controlled asymmetric additions to CN double bond. An efficient approach to stereochemically defined α-fluoroalkyl amino compounds

Abstract This paper presents a full account of studies into the asymmetric addition reactions between α-lithium derivatives of enantiomerically pure methyl and benzyl p-tolyl sulfoxides and the N-(p-methoxyphenyl)aldimines, bearing trifluoromethyl, pentafluoroethyl and ω-hydrotetrafluoroethyl groups, to afford the corresponding α-fluoroalkyl β-sulfinylamines, synthetically versatile precursors of a series of enantiomerically pure biomedicinally important α-fluoroalkylalkylamines and α-fluoroalkyl-β-hydroxyalkylamines. The addition reactions were found to proceed under mild conditions allowing for convenient preparation of the corresponding α-fluoroalkyl β-sulfinylamines in excellent yields and good enantiomeric purity. The stereochemical outcomes of these reactions were shown to be subject to kinetic control, that is in sharp contrast to the corresponding reactions of fluorine-free imines. The absolute configurations of the addition products suggest that the fluoroalkyl group on starting imines plays a role of enantiodirecting, sterically larger substituent causing realization of an unusual for this type of reactions transition states.

Novel way of separating polyfluorocarboxylic acids by ion-exclusion chromatography

Ion-exclusion chromatography has been successfully applied to the separation of a number of polyfluorocarboxylic acids. The separation of various mono- and dibasic polyfluorocarboxylic acids having a different alkyl group was investigated using a polymethacrylate-based weakly acidic cation-exchange resin (TSK gel OApak-A) in the H -form and conductimetric detection. When water was used as the eluent, polyfluorocarboxylic acids could not be resolved. When an aqueous solution of sulfuric acid, benzoic acid, o-phthalic acid, 1,3,5-benzenetricarboxylic acid, 1,2,4,5-benzenetetracarboxylic acid, and tartaric acid was used, the separation of polyfluorocarboxylic acids occurred for monobasic ones. While, for fluorine-containing dibasic acids, imperfect separation of peaks occurred. In order to improve their separation, the effect of an addition of organic modifiers such as methanol, 2,2,2-trifluoroethanol and 2H-hexafluoro-2-propanol in the eluent was also investigated.

Electrochemical fluorination of N-containing carboxylic acids Part 5. Fluorination of the methyl esters of cis-2,6-dimethylmorpholino-group substituted carboxylic acids

Abstract Cis -2,6-dimethylmorpholine and its derivatives having an ester group were subjected to electrochemical fluorination. The electrochemical fluorination of cis -2,6-dimethylmorpholine afforded only a small quantity of F -( N -fluoro-2,6-dimethyl-morpholine), whereas the N -(methoxycarbonylalkyl)-substituted cis -2,6-dimethyl-morpholines gave the corresponding F -acid fluorides in fair yields. Cis -and trans -isomerization on two methyl substituents of the morpholine ring occurred through electrochemical fluorination of pure cis -2,6-dimethylmorpholine to give a 1:0.25–0.5 mixture of cis - and trans -isomers having a F -2,6-dimethylmorpholino-moiety. The formation of a seven-membered ring expanded product was confirmed as a by-product in the fluorination of methyl cis -2,6-dimethylmorpholino-acetate. Spectroscopic data as well as physical properties of new nitrogen-containing F -carboxylic acids are presented.

ELECTROCHEMICAL FLUORINATION OF DI- AND TRI-(2-HYDROXYETHYL)-SUBSTITUTED ALKYLAMINES

Abstract Several 2-(hydroxyethyl)-substituted alkylamines like 1,4-bis(2-hydroxyethyl)piperazine, N , N -bis(2-hydroxyethyl)methylamine, N , N -bis(2-hydroxyethyl)ethylamine, and N , N , N -tris(2-hydroxyethyl)amine as well as their derivatives (HCl salts, a borate and trimethylsilylethers) were subjected to electrochemical fluorination. From 1,4-bis(2-hydroxyethyl)piperazine, F -[1,4-bis(fluorocarbonylmethyl)piperazine] was obtained in low yield. In the fluorination of N , N -bis(2-hydroxyethyl)alkylamines and N , N , N -tris(2-hydroxyethyl)amine, cyclization occurred extensively, affording large quantities of F -morpholine derivatives. However, F - N , N -bis(fluorocarbonylmethyl)methylamine was obtained from the former in low, isolated yield.

Electrochemical fluorination of (N,N-dialkylamino)alcohols

Abstract Series of amino alcohols including 2-( N,N -dialkylamino)ethanols, 3-( N,N -dimethylamino)propanol and 4-( N,N -dimethylamino)butanol were subjected to electrochemical fluorination. In the case of 2-( N,N -dialkylamino)ethanols, the F -(2- N,N -dialkylamino)acetyl fluorides were obtained in fair to good yields. Yields of each target compound were strongly dependent on the kind of the dialkylamino group. Cyclic amines having an N -(2-hydroxylethyl) group afforded the corresponding F -[ N -( c -alkylamino)-substituted acetyl fluorides]. Their yields were generally better than those of acyclic analogs. Several 2-( N,N -dialkylamino)ethanols and 3-( N,N -dimethylamino)propanol were converted into the corresponding trimethylsilylethers, aminoalkyl methyl carbonates and bis-aminoalkyl carbonate, respectively, and they were subjected to fluorination for a comparison of the yield with that obtained from that of the parent aminoalcohol.

Electrochemical fluorination of several 1,4-bis[(methoxycarbonyl)alkyl] substituted piperazines

Abstract Four piperazines, having bis[(methoxycarbonyl)alkyl] groups ( CH 2 CH 2 C(O)OMe ( 1 ), CH(CH 3 )C(O)OMe ( 2 ), CH 2 CH(CH 3 )C(O)OMe ( 3 ) and CH(CH 3 )CH 2 C(O)OMe ( 4 ) at the 1- and 4-positions of the piperazine ring), were subjected to electrochemical fluorination (ECF). Two bis[(methoxycarbonyl)alkyl] derivatives of N,N′ -dimethylethylenediamine (molecular formulae: MeO(O)CH 2 CH 2 N(CH 3 )CH 2 CH 2 N(CH 3 )CH 2 CH 2 C(O)OMe ( 5 ) and MeO(O)CH(CH 3 )CH 2 N(CH 3 )CH 2 CH 2 N(CH 3 )CH 2 CH(CH 3 )C(O)OMe] ( 6 )) were also similarly fluorinated for a comparative study. On ECF of piperazine derivatives ( 1 – 4 ), the corresponding perfluoropiperazines having bis[(fluorocarbonyl)perfluoroalkyl] groups were formed, while the ECF of the substrates 5 and 6 afforded degraded products only. Yields of the targeted di-basic perfluoroacid fluorides containing a perfluoropiperazinyl group varied, depending on the type of bis[(methoxycarbonyl)alkyl] groups at the 1- and 4-positions. The best yield of the di-basic perfluoroacid fluorides was obtained from the ECF of 1,4-bis[2-(methoxycarbonyl)propyl]piperazine ( 3 ). Spectroscopic data as well as physicochemical properties are described for new perfluoroacid fluorides and perfluoro(1,4-dialkylpiperazines).

Electrochemical fluorination of 1-ethylpiperazine and 4-methyl- and/or 4-ethylpiperazinyl substituted carboxylic acid methyl esters

Abstract Electrochemical fluorination (ECF) of 1-ethylpiperazine and eight methyl esters of 4-methyl- and/or 4-ethylpiperazinyl substituted carboxylic acids were studied. Corresponding perfluoro(4-fluoro-1-ethylpiperazine) was obtained from 1-ethylpiperazine in a small yield along with perfluoro(1-methyl-3-ethylimidazolidine), perfluoro[2-( N′,N′- difluoroaminoethyl) -N,N -diethylamine)] and perfluorotriethylamine. The corresponding mono-basic perfluoroacid fluorides with a perfluoro(4-alkylpiperazinyl) group were obtained in fair to good yields from the fluorination of methyl esters of 4-alkylpiperazinyl-substituted carboxylic acids. Yields of the targeted perfluoro(4-alkylpiperazinyl) group containing perfluorocarboxylic acid fluorides varied depending on both the type of N -alkyl (alkyl=CH 3 − or C 2 H 5 − ) group at the 4-position and the (ω-methoxycarbonylalkyl) group at the 1-position of the piperazine ring of the substrate. Higher yields of perfluoroacid fluorides were obtained by the ECF of 4-ethyl substituted piperazine derivatives than of the 4-methyl substituted piperazine derivatives when 4-alkylpiperazines with the same carboxylic acid ester group were fluorinated electrochemically. Spectroscopic data as well as physical properties are described for new perfluoro(1,4-dialkylpiperazines) and N -containing perfluorocarboxylic acids with a perfluoropiperazinyl group.