Synthesis and frustrated phases of chiral liquid crystals derived from (R)-3-alkoxy-2-methylpropionic acids

A homologous series of chiral compounds, (R)-6-(3-alkoxy-2-methylpropionyloxy)-2-naphthyl 4-alkoxybenzoates, nMPNmB (n = 2-5, m = 6-13), derived from methyl (R)-3-hydroxy-2-methylpropionate, was prepared for the study of mesormorphic phases. The mesophases were determined mainly by their microscopic textures and identified by the racemic modification. The results show that most of these compounds displayed frustrated phases BP, TGB_A* and TGB_C*, and the N*phase. Moreover, the thermal stability of the frustrated phases is significantly affected by the length of the alkyl chain in both achiral and chiral groups of the compounds. The spontaneous polarization in the TGB_C* phase of compounds nMPN10B in a surface-stabilized geometry was measured, giving P_s values of about 20 nC cm^-2.     

Stable frustrated phases in chiral liquid crystals derived from optically active (R)- and (S)-3-ethylmercapto-2-methylpropionic acids

Highly optically pure (R)- and (S)-3-ethylmercapto-2-methylpropionic acids were synthesized by using optically active (D)- and (L)-2,10-camphorsultams as chiral auxiliaries, respectively. Their derivatives, (R)- and (S)-EMMPNmB (m=6-12), were prepared for investigation. Microscopic texture observations demonstrated that the materials possess three stable frustrated phases: BP, TGB_A* and TGB_C* phases. Interestingly, it was found that the N* phase behaves as an intermediary phase between BP and TGB_A* phases in a rather narrow temperature range (calc. 0.5-1.4°C). A study of the racemic mixture, (±)-EMMPNmB (m=10), indicated that the chirality of the molecule could suppress the formation of smectic phases in the heating process. An increase of alkyl chain length favoured the formation of the TGB phases particularly, in accompaniment with a change of TGB phases from monotropic to enantiotropic. Moderate maximum P _S values (calc. 14-19 nC cm^-2) and apparent tilt angle (calc. 20°) were obtained for the TGB_C* phase in a surface stabilized ferroelectric liquid crystal geometry.     

Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. ¹H NMR spectroscopy was employed to investigate their enantiodiscriminating ability. Compared with α-phenylethylamine, a commercially available chiral solvating agent (CSA), these compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as promising and practical CSAs.     

Asymmetric synthesis of (R)- and (S)-4-methyloctanoic acids. A new route to chiral fatty acids with remote stereocenters

The enantioselective synthesis of both enantiomers of 4-methyloctanoic acid, one major aggregation pheromone component of the rhinoceros beetles of the genus Oryctes and an important aroma compound, is described. The key step of the synthesis is based on a stereospecific alkylation with an alcohol-protected alkyl iodide using a pseudoephedrine derivative as a chiral auxiliary followed by subsequent removal of the auxiliary. Both enantiomers are obtained in excellent yields and enantioselectivities (93–94% ee). The strategy outlined allows preparation of a wide variety of enantiopure methyl-branched saturated and unsaturated fatty acids.     

Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid

The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).     

Novel glassy nematic and chiral nematic oligomers derived from 1,3,5-cyclohexanetricarboxylic and (1R,3S)-( )-camphoric acids

Novel nematic and chiral nematic liquid crystals capable of vitrification have been synthesized using 1,3,5-cyclohexanetricarboxylic and (1R,3S)-(+)-camphoric acids as the base structures to which cyanotolan, cyanobiphenyl, methoxybiphenylbenzoate nematogenic groups, (S)-(-)-1-phenylethylamine and (S)-(+)-1,3-butanediol chiral moieties are attached. Once the glassy state is induced by quenching or controlled cooling from the isotropic state, these liquid crystals showed no detectable tendency towards crystallization upon heating through the glass transition temperature. In all cases, the ΔC_p and ΔH_c values resulting from the DSC heating scans are comparable to those previously reported for polymer analogues and other low molar mass glassy liquid crystals. In the nematic series with varying spacer lengths, both T_g and T_c are consistently lower than the linear polymer counterparts, in contrast to the siloxane-based systems. It was also demonstrated that cholesteric mesomorphism can be induced following one of the three approaches: chiral nematic mixture, chiral nematic cyclic cooligomer, and pendant nematogenic groups attached to a chiral ring.     

Mesogenic properties of chiral compounds derived from 2( S )-[2( S )-ethylhexyloxy] propionic acid and its ( S, R )-diastereomer

Two acids, 2( S )-[2( S )-ethylhexyloxy] propionic acid and 2( S )-[2( R )-ethylhexyloxy] propionic acid, were used as the chiral building block for the preparation of four liquid crystals 5, 6, 7 and 8 . The diastereomers of the biphenyl ring system, 5 and 6 , possess the phase sequence I-N * -SmC * -Cr1-Cr2, while the diastereomers of the naphthalene ring system, 7 and 8 , exhibit the sequence I-SmA-SmC * -Cr. The temperature ranges of the SmC * phase for 5 and 6 are wider than those for 7 and 8 ; the phase transition temperatures of the SmC * phase for 7 and 8 are lower than those for 5 and 6 . In the case of the diastereomers of naphthalene ring system, the larger the size of the lateral substituent at the second chiral centre, i.e. ethyl or methyl group, the wider the temperature range of the SmC * phase.     

A practical and efficient synthesis of chiral N,N-disubstituted C2 symmetric diamines derived from (R,R)-1,2-diaminocyclohexane

An improved synthesis of chiral diamine ligands derived from (R,R)-1,2-diaminocyclohexane is described, providing N-substituted diamines. The synthesis of other new ligands based on this methodology is also reported.     

New chiral auxiliaries derived from (S)-α-phenylethylamine as chiral solvating agents for carboxylic acids

The two new diastereoisomeric chiral auxiliaries 1a and 1b were synthesized conveniently and effectively. ¹H NMR was employed to investigate their chiral recognition ability. Compared with (S)-PEA, these new chiral auxiliaries exhibited better enantioselectivity towards the carboxylic acids we had chosen.     

Straightforward synthesis of (S)- and (R)-alpha-trifluoromethyl proline from chiral oxazolidines derived from ethyl trifluoropyruvate

[Structure: see text] A concise synthesis of both enantiomers of alpha-Tfm-proline and (S)-alpha-Tfm-prolinol from ethyl trifluoropyruvate is reported. The key step is a diastereoselective allylation reaction of ethyl trifluoropyruvate and (R)-phenylglycinol-based oxazolidines or imine. The lactone obtained by cyclization of the resulting hydroxy ester proved to be a valuable intermediate for the synthesis of (S)-alpha-Tfm-allylglycine and (S)-alpha-Tfm-norvaline in enantiopure form.     

A useful chiral synthon from (R)-4-menthenone

Russian Chemical Bulletin -     

Liquid chromatographic resolution of 2-hydroxycarboxylic acids on a new chiral stationary phase derived from (S)-leucine

Enantiomers of racemic 2-hydroxycarboxylic acids have been resolved as their O-ethoxycarbonyl pi-basic anilide derivatives on a new chiral stationary phase (CSP) derived from N-(3,5-dinitrobenzoyl)leucine N-phenyl N-alkylamide and the resolution results have been compared with those on various commercial pi-acidic CSPs. The resolution results demonstrate that the new CSP derived from N-(3,5-dinitrobenzoyl)leucine N-phenyl N-alkylamide is most effective among the five CSPs tested for the resolution of 2-hydroxycarboxylic acid derivatives. In order to elucidate the chiral recognition mechanism exerted by the new CSP, the resolution of slightly differently modified derivatives of 2-hydroxycarboxylic acids on the new CSP has been investigated. Based on the resolution results, a chiral recognition mechanism utilizing three simultaneous interactions such as the face to face pi-pi interaction and the two hydrogen bonding interactions between the CSP and the more retained enantiomer of the analyte has been proposed.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

A new chiral diol derived from tetralone for the complexation of Lewis acids

A new approach to the rational design of Lewis acids based on face-face π-π interactions is described. The synthesis of two novel diols (−)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol (−)-1 and (−)(1S,3R)-trans-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1-3-diol (−)-9 is reported in six and five steps respectively starting from α-tetralone. Complexation of (−)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol (−)-1 to phenylboronic acid shows the interplanar distance between the boron atom and the aromatic ring to be 3.05 Å, which is ideal for the proposed interactions.     

Synthesis of chiral 1,5-disubstituted pyrrolidinones via electrophile-induced cyclization of 2-(3-butenyl)oxazolines derived from (1R,2S)- and (1S,2R)-norephedrine

Starting from (1R,2S)- and (1S,2R)-norephedrine, enantiomers of the corresponding 2-(3-butenyl)oxazolines were prepared in a two-step process. The cyclization of the intermediate alkenylamides with phenylselenyl bromide afforded cyclic imidates instead of the expected pyrrolidinones. The electrophile-induced cyclizations of 2-alkenyloxazolines with bromine or iodine produced diastereomeric mixtures of chiral 1,5-disubstituted pyrrolidinones. The ring closure of the all-cis (1R,2S,5R)-diastereomer 7 with NaH resulted in the tetrahydropyrrolo[2,1-b]oxazol-5-one derivative 18, which was alternatively prepared by the cyclocondensation of (1R,2S)-norephedrine with levulinic acid.     

Synthesis of a new (1R)-(-)-myrtenal-derived dioxadithiadodecacycle and its use as an efficient chiral auxiliary

[reaction: see text] The new macrocycle 9 (>70% yield from hydroxythiol 10) was treated with several nucleophilic reagents (RMgX, RLi, and LiAlH4) affording carbinols 12a-j (80-96% yield, >99:1 dr). Oxidative hydrolysis of 12a,c,e, followed by LiAlH4 reduction of the resulting mixture, gave 16a,c,e in >95% ee,16c being a key precursor for the preparation of fungicide 17. The absolute configuration of 9 and 12j (Nu = H) was established by single-crystal X-ray diffraction analyses and chemical correlation.     

Synthesis and asymmetric catalytic application of chiral imidazolium–phosphines derived from (1R,2R)-trans-diaminocyclohexane

Reaction between a chiral imidazole–amine precursor derived from (1R,2R)-trans-diaminocyclohexane and P¹Cl (where P¹ = PPh₂, P(1,3,5-Me₃C₆H₃)₂, P(2,2′-O,O′-(1,1′-biphenyl), P((R)-(2,2′-O,O′-(1,1′-binaphthyl))) and P((S)-(2,2′-O,O′-(1,1′-binaphthyl)))) followed by RX (where R = ⁿPr, ⁱPr, CHPh₂, X = Br; R = ⁱPr, X = I), respectively, gives a selection of chiral imidazolium–phosphine compounds. Deprotonation of the imidazolium salt gives the corresponding NHC–P ligands that can be used in metal-mediated asymmetric catalytic applications. Catalytic reactions show that NHC–P ligands give a significantly greater rate of reaction for a palladium catalysed allylic substitution reaction in comparison to analogous di-NHC or NHC–imine ligands and that NHC–P hybrids are also effective for iridium catalysed transfer hydrogenation.     

Lanthanide complexes of chiral 3 + 3 macrocycles derived from (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol

The enantiopure amine macrocycle H(3)L, as well as the parent macrocyclic Schiff base H(3)L1, the 3 + 3 condensation product of (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol, are able to form mononuclear complexes with lanthanide(III) ions. The lanthanide(III) complexes of H(3)L have been studied in solution using NMR spectroscopy and electrospray mass spectrometry. The NMR spectra indicate the presence of complexes of low C(1) and C(2) symmetry. The (1)H and (13)C NMR signals of the Lu(III) complex obtained from H(3)L have been assigned on the basis of COSY, TOCSY, NOESY, ROESY and HMQC spectra. The NMR data reveal unsymmetrical binding of lanthanide(III) ion and the presence of a dynamic process corresponding to rotation of Lu(III) within the macrocycle. The [Ln(H(4)L)(NO(3))(2)](NO(3))(2)(Ln = Sm(III), Eu(III), Dy(III), Yb(III) and Lu(III)) complexes of the cationic ligand H(4)L(+) have been isolated in pure form. The X-ray analysis of the [Eu(H(4)L)(NO(3))(2)](NO(3))(2) complex confirms the coordination mode of the macrocycle determined on the basis of NMR results. In this complex the europium(III) ion is bound to three phenolate oxygen atoms and two amine nitrogen atoms of the monoprotonated macrocycle H(4)L(+), as well as to two axial bidendate nitrate anions. In the presence of a base, mononuclear La(III), Ce(III) and Pr(III) complexes of the deprotonated form of the ligand L(3-) can be obtained. When 2 equivalents of Pr(III) are used in this synthesis Na(3)[Pr(2)L(NO(3))(2)(OH)(2)](2)NO(3).5H(2)O is obtained. The NMR, ES MS and an X-ray crystal model of this complex show coordination of two Pr(III) ions by the macrocycle L. The X-ray crystal structure of the free macrocycle H(3)L1 has also been determined. In contrast to macrocyclic amine H(3)L, the Schiff base H(3)L1 adopts a cone-type conformation resembling calixarenes.     

A new route to (2S,4R)- and (2R,4S)-4-hydroxypipecolic acid

Both enantiomers of cis-4-hydroxypipecolic acid have been prepared by asymmetric synthesis using (S)- or (R)-glycidol as the chiral source, and involving a stereoselective hydrogenation of a six-membered cyclic imine. The latter is obtained by reduction and cyclization of a cyano β-hydroxy ketone.     

New chiral amino-phosphoramidite and bisphosphoramidite ligands derived from (R,R)-1,2-diaminocyclohexane: application in Cu-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone

New bidentate amino-phosphoroamidite and diphosphoroamidite ligands derived from inexpensive (R,R)-1,2-diaminocyclohexane have been synthesized and screened in the Cu-catalyzed asymmetric conjugate addition of Et₂Zn to 2-cyclohexenone. The highest 74% ee value was reached with the N,N′-dimethyl substituted P,N-ligand and Cu(OAc)₂·H₂O.