Tris-chelate complexes with chiral ligands: In search of diastereoisomeric selectivity with remote stereogenic centres

The chiral ligands, 4,4′-bis{(1S,2R,4S)-(−)-bornyloxy}-2,2′-bipyridine, (1S,2R,4S)-1, and 4,4′-bis{(1R,2S,4R)-(+)-bornyloxy}-2,2′-bipyridine, (1R,2S,4R)-1, have been prepared and characterized by spectroscopic techniques and, for (1S,2R,4S)-1, by single crystal X-ray diffraction. Despite the use of enantiomerically pure ligands, the formation of the complexes [Fe((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)(bpy)₂]²⁺ and [Ru((1R,2S,4R)-1)(bpy)₂]²⁺ proceeds without preference for either the Δ or Λ-diastereoisomers.     

Asymmetric transfer hydrogenation of ferrocenyl ketones: a new simple route to chiral ferrocenyl alcohols

The asymmetric transfer hydrogenation (ATH) of ferrocenyl ketones, such as FcC(O)CH₂Y [Fc = ferrocenyl, Y = H (1a), CH₃ (1b), Cl (1c) or N₃ (1d)] has been carried out using the Noyori/Ikariya catalysts [(−)-(1R,2S)-ephedrine] or N-tosyl-(1R,2R)-diphenylethylenediamine [(R,R)-TsDPEN] as chiral ligands combined with [RuCl₂(η⁶-benzene)]₂ and 2-PrOH or HCO₂H–Et₃N as the hydrogen sources, respectively. The best results were achieved with the [(R,R)-TsDPEN–Ru^IIHCO₂H–Et₃N] catalytic system, which produced the ferrocenylalcohols (R)-2a, (R)-2c, and (R)-2d in good yields and excellent enantiomeric excesses (>98% ee).     

Synthesis of 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] and derivatives: precursors of long-chain polyketides

Racemic 1,1′-methylene[(1RS,1′RS,3RS,3′RS,5RS,5′RS)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] ((±)-6) derived from 2,2′-methylenedifuran has been resolved kinetically with Candida cyclindracea lipase-catalysed transesterification giving 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] (−)-6 (30% yield, 98% ee) and 1,1′-methylenedi[(1S,1′S,3S,3′S,5S,5′S)-8-oxabicyclo[3.2.1]oct-6-en-3-yl] diacetate (+)-8, (40% yield, 98% ee). These compounds have been converted into 1,1′-methylenedi[(4S,4′S,6S,6′S)- and (4R,4′R,6R,6′R)-cyclohept-1-en-4,6-diyl] derivatives.     

Polyhydroxylated pyrrolizidines. Part 3: A new and short enantiospecific synthesis of (+)-hyacinthacine A2

(1R,2R,3R,7aR)-1,2-Dihydroxy-3-hydroxymethylpyrrolizidine (+)-Hyacinthacine A₂ 1 has been synthesized by Wittig's methodology using [(2′S,3′R,4′R,5′R)-3′,4′-dibenzyloxy-N-tert-butyloxycarbonyl-5′-tert-butyldiphenylsilyloxymethylpyrrolidin-2′-yl]carbaldehyde 3, prepared from a partially protected DMDP 2, and the appropriated ylide, followed by cyclization by an internal reductive amination process of the resulting unsaturated aldehyde 4 and total deprotection.     

Dynamic behaviour and X-ray analysis of chiral η-allylpalladium complexes. II

The DANTE technique and NOESY two-dimensional method have been employed to observe the isomerization of the chiral cationic complex [Pd(η³-CH₂CMeCH₂(P-P′)]⁺ (1a), where P-P′ = the chiral chelating ligand (S)(N-diphenylphosphino)(2-diphenylphosphinoxymethyl)pyrrolidine. The rate constant was found to be 0.5 s⁻¹ in CHCl₃ at 295 K and 1.50 s⁻¹ in the presence of added free ligand. In the latter case the epimerization proceeds by a π-σ-π mechanism via the intermediacy of a primary η¹-allylpalladium complex. Although the intermediate was not detected, the NMR findings reveal that it has the allylic terminus η¹-bonded to palladium. The structure of 1a in its PF₆⁻ salt has been determined. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ with a 10.029(4) b 19.203(8) c 36.115(6) Å, Z = 8, R = 0.0572 and R_w = 0.0712 for 3716 observed reflections with I > 3σ(I).     

Asymmetric radical additions using chiral 1,3-dioxolane-4-ones

Moderate facial selectivities are observed in additions of alkyl radicals to the chiral (c,d) olefin (2S)-2-tert-butyl-5-ethoxycarbonylmethylene-1,3-dioxolane-4-one 1. The following hydrogen abstraction from tributylstannane proceeds with excellent asymmetric stereocontrol, leading to two of four possible diastereoisomers with high diastereomeric excesses. Additions of chiral radicals obtained from (2R,5R)-5-alkyl-5-bromo-1,3-dioxolane-4-ones to ethyl acrylate show high asymmetric 1,3-induction.     

Stereochemical studies of optically active 2-hydroxy-5-alkyl-δ-valerolactone derivatives as chiral dopant for ferroelectric liquid crystals

Both (2S, 5R)- and (2R, 5R)-2-hydroxy-5-alkyl-δ-valerolactone derivatives, cis and trans, respectively, show almost the same magnitude of spontaneous polarization (P_s) when added to a non-chiral smectic C mixture. The stereochemistry of these chiral dopants was studied using ¹H NMR. Trans derivatives seem to have a half-chair conformation with the 2, 5-diequatorial substituents and the cis derivatives have rather a flat conformation in solution. However in the liquid-crystalline phase, the cis and trans derivatives appear to change their conformation or the distribution of their conformations as the alkyl chain length is varied. The difference in the effect as a chiral dopant depends upon lateral interactions between chiral molecules through the solvent liquid crystal phase.     

Inokosterone, an insect metamorphosing substance from Achyranthes fauriei : Absolute configuration and synthesis

Inokosterone, a phytoecdysone isolated from Achyranthes fauriei (Amaranthaceae), has been partially acetylated to give the 2,26-diacetate (4) which has been converted into methyl 5 - acetoxy - 4 - methylpentanoate (7), showing no apparent []_D, and 2β - acetoxy - 3β,14 - dihydroxy - 5β - pregn - 7 - ene - 6,20 - dione (8). Chemical and physiochemical studies have shown the configurations at C-20 and C-22 to be R. Inokosterone has thus been concluded to be a mixture of C-25 epimers of (20R,22R) - 2β,3β,14,20,22,26 - hexahydroxy - 5β - cholest - 7 - en - 6 - one (1). After the synthesis of the model compound, a C-25 epimeric mixture of (20R,22R) - 3β,20,22,26 - tetrahydroxy - 5 - cholestane (23), inokosterone has been synthesized via (20R) - 2β,3β,14,20 - tetrahydroxy - 20 - formyl - 5β - pregn - 7 - en - 6 - one (25) by Grignard reaction with 4 - (tetrahydrofuran - 2 - yloxy) - 3 - methylbutynylmagnesium bromide (15) followed by hydrogenation and hydrolysis. The use of an NMR shift reagent with the inokosterone acetates (9, 29) and the optical activity measurement of - methylglutaric acid (3) derived from inokosterone have established that inokosterone is a 1:2 mixture of the C-25 R and S epimers.     

Ferroelectric liquid crystals induced by atropisomeric biphenyl dopants: the effect of chiral perturbations on achiral dopants

The addition of the achiral biphenyl dopant 2,2',6,6'-tetramethyl-4,4'-bis(4-n-nonyloxybenzoyloxy)biphenyl (3) or its dithionoester or dithioester analogue (4, 5) to a 4 mol % mixture of the atropisomeric biphenyl dopant (R)-2,2',6,6'-tetramethyl-3,3'-dinitro-4,4'-bis(4-n-nonyloxybenzoyloxy)biphenyl, (R)-1, in the phenylpyrimidine SmC host PhP1 produces a significant amplification of the spontaneous polarization induced by (R)-1. This amplification may be due to a chiral perturbation by (R)-1 which causes a shift in the equilibrium between enantiomeric conformations of the achiral dopant. The degree of polarization amplification afforded by the achiral dopant, as expressed by the polarization amplification factor PAF, varies with the nature of the linking group. This may be ascribed to different rotational distributions of the core transverse dipole moments relative to the polar axis of the SmC* phase and/or to differences in lateral bulk of the polar linking groups. The latter may affect the degree of chiral molecular recognition achieved by 3-5 in the binding site of the SmC* phase.     

Ferroelectric liquid crystals induced by dopants with axially chiral 2,2'-spirobiindan-1,1'-dione cores: diether vs. diester side-chains

A series of axially chiral 5,5'- and 6,6'-dialkanoyloxy-2,2'-spirobiindan-1,1'-dione dopants, (R)-2 and (R)-4a-4c were synthesized in optically pure form and their ferroelectric polarization powers, δ_p, measured in four liquid crystal hosts with isotropic (I)-nematic (N)-smectic A (SmA)-smectic C (SmC) phase sequences. The results show that the sign of polarization P _S induced by (R)-2 and (R)-4a-4c follows the same trend as that previously reported for the 5,5'- and 6,6'-diheptyloxy-2,2'-spirobiindan-1,1'-dione dopants, (R)-1 and (R)-3. The polarization induced by (R)-2 in the host DFT is below detection limits, and the sign of P _S was found to invert as a function of temperature at mole fractions as low as 0.01. On the other hand, the polarization power of the 6,6'-diheptanoyloxy dopant (R)-4b in the host NCB76 is -1449 nC cm^-2, the fourth highest value reported so far, and more than three times the δ_p value of the 5,5'-diheptanoyloxy analogue (R)-2 in that host (+474 nC cm^-2). Results of ²H NMR experiments suggest that (R)-4b exerts stronger local perturbations in NCB76 than (R)-2, and that these perturbations may be chiral in nature.     

Antiferroelectric liquid crystals derived from a new optically active (R)-3-ethylmercapto-2-methylpropionic acid

A new optically active (R)-3-ethylmercapto-2-methylpropionic acid has been synthesized using D(-)—2,10-camphorsultam as a chiral auxiliary. The optical purity of the acid obtained was greater than 98 per cent. Its derivatives, (R)-4-(3-ethylmercapto-2-methylpropionyl)phenyl 4'-alkoxybiphenyl-4-carboxylates (EMMPPmBC; m = 7-16), have been prepared for the investigation of liquid crystalline properties as a function of peripheral alkyl chain length. Optical studies showed that all members exhibited an antiferroelectric S*c_A phase. The results also indicate that a lengthened alkyl chain length is favoured for S_cA* phase formation.     

Enantiodivergent synthesis of 3-amino-4,4-dimethyl-1-phenylpyrrolidin-2-one and derivatives: amino analogues of pantolactone

An enantiodivergent preparation of (+)-(R)- and (−)-(S)-3-amino-4,4-dimethyl-1-phenylpyrrolidin-2-one, (R)- and (S)-9, and several derivatives, from 4,4-dimethyl-1-phenylpyrrolidin-2,3-dione, 4, and (R)- or (S)-1-phenylethylamine, (R)- or (S)-5, as the chirality transfer agents, is described. Amine (S)-9 has also been used as a chiral auxiliary in a diastereoselective Michael reaction.     

Diastereoselective synthesis of a resolved secondary arsine complex: asymmetric synthesis of (R-(−)589-ethylmethylphenylarsine

The reaction of [R-(R,R)]-(+)₅₈₉-[(η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}Fe(NCMe)]PF₆ with (±)-AsHMePh in boiling methanol yields crystalline [R-[(R)-(R,R)]-(+)_{589)-[(η⁵-C5H5){1,2-C6H4(PMePh)2}Fe(AsHMePH)}PF₆, optically pure, in ca. 90% yield, in a typical second-order asymmetric transformation. This complex contains the first resolved secondary arsine. Deprotonation of the secondary arsine complex with KOBu^t at −65°C gives the diastereomerically pure tertiary arsenido-iron complex [R-[(R),(R,R)]]-[((η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}FeAsMePh] · thf, from which optically pure [R-[(S),(R,R)]]-(+)₅₈₉-[(η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}Fe(AsEtMePh)PF₆ is obtained by reaction with iodoethane. Cyanide displaces (R)-(−)₅₈₉-ethylmethylphenylarsine from the iron complex, thereby effecting the asymmetric synthesis of a tertiary arsine, chiral at arsenic, from (±)-methylphenylarsine and an optically active transition metal auxiliary.     

Preparation and crystal structure of a 1:1 inclusion compound of 1,4,11,14-tetramethoxy-dibenzo[b,n]tetraphenylene with pyridine

The new host 1,4,11,14-tetramethoxy-dibenzo[b,n]tetraphenylene forms a 1:1 inclusion compound with pyridine, in which a pair of centrosymmetrically-related guest species are enclosed in the cage surrounded by six host molecules. C₃₆H₂₈O₄·C₅H₅N, F_W=603.68, triclinic, space group P-1, a=11.796(2), b=16.075(3), c=9.004(2) Å; =98.39(3)°, β=90.01(3)°, γ=108.19(3)°, V=1602.8(5) Å³, Z=2, F(000)=636, D_c=1.251 g/cm³, μ=0.080 mm⁻¹. The final R indices [I>2σ(I)] R₁=0.0759, wR₂=0.1970 for 5623 MoK observed data.     

(R)-Binaphthoxy diiodide lanthanides

The synthesis and characterization of novel enantiopure binaphthoxy-diiodo lanthanides [(R)-2-(1-naphthol)-1′-naphthoxide)LnI₂(THF)₃] (Ln=Sm (4a), Yb (4b), La (4c)) are described. These complexes have been prepared by reacting the mono potassium salt of (R)-binaphthol with the corresponding lanthanide triiodides and were characterized by elemental analysis, IR and NMR spectroscopies. Recrystallization of 4c from THF–hexane led to monocrystals of [(R)-2-(1-naphthol)-1′-naphthoxide)]-diiodolanthane-tetrakistetrahydrofurane] (4c*). Complex 4c* crystallizes in the orthorhombic space group, P2₁2₁2₁ with cell parameters a=13.086(1) Å, b=15.496(1) Å, c=18.854(1) Å, V=3823.2(6) ų, and Z=4.     

Synthesis of four enantiomerically pure 4-(4-carbamoyl-1,2,3-triazol-1-yl)-2,3-dihydroxy-1-methoxybutylphosphonic acids

CuCl-catalysed cycloaddition of methyl propiolate to O,O-diisopropyl (1S,2R,3S)- and (1R,2R,3S)-, or O,O-dibenzyl (1S,2R,3S)-, (1R,2R,3S)-, (1S,2R,3R)- and (1R,2R,3R)-4-azido-1,2,3-trihydroxy-2,3-O-isopropylidenebutylphosphonates followed by methylation of HO–C-1, ammonolysis of methoxycarbonyl groups and hydrolysis of isopropylidene acetals led to diisopropyl (1S,2R,3S)- and (1R,2R,3S)-4-(4-carbamoyl-1,2,3-triazol-1-yl)-2,3-dihydroxy-1-methoxybutylphosphonates or, after hydrogenolytic removal of benzyl groups, to (1S,2R,3S)-, (1R,2R,3S)-, (1S,2R,3R)- and (1R,2R,3R)-4-(4-carbamoyl-1,2,3-triazol-1-yl)-2,3-dihydroxy-1-methoxybutylphosphonic acids.     

Unusual sulfated marine steroids from the ophiuroid ophioderma longicaudum

Polar extracts of the ophiuroid Ophioderma longicaudun contain unusual sterol sulfates together with a mixture of common 3β-hydroxysterol sulfates. The more polar compound has been shown to be 5β-cholestane-3, 4,11β,12β,21-pentol 3,21-disulfate 1. A second group of unusual compounds are disulfated 3,21-dihydroxysteroids. After solvolysis to remove the sulfate groups they have been identified as : (20R)-5-cholestane-3, 21-diol 4a, (20R)-cholest-5-ene-3,21-diol 5a, (20R22E)-cholest-5,22-diene-3,21-diol 6a and (20R)-24-methylcholest-5,24(28)-diene-3,21-diol 7a. Analysis of the “non-sulfated” sterol fractions has shown the presence of common 3β-hydroxy sterols.     

Enantioselektive Katalyse VII. Komplexe von (P(R,S),3R,4R,P′(R,S))-3,4-Bis(phenylphosphino)pyrrolidinen. Die Darstellung optisch reiner 1,2-Bisphosphanliganden mit vier Stereozentren, die zusätzliche funktionnelle Gruppen enthalten

Diastereomeric mixtures of the palladium, the platinum, and the rhodium complexes were prepared from [P(R,S),3R,4R,P′(R,S)]-3,4-bis(phenylphosphino)pyrrolidine (1a). The phosphorus atoms in bis[(P(R,S),3R,4R,P′(R,S))-1-(t-butoxycarbonyl)-3,4-bis(phenylphosphino)pyrrolidine-P,P′]dihalogenopalladium (2) can be alkylated stereoselectively with iodomethane. The P---H bonds in 2 open epoxides, and add to Michael systems, to give new ligands, which can be split off from the palladium with cyanide. The three isomerically pure [(PR,3R,4R,P′R)(PS,3R,4R,P′S)(PR,3R,4R,P′S)]-1-(t-butoxycarbonyl)-3,4- bis[(2-cyanoethyl)phenylphosphino]pyrrolidines were prepared via the neutral diiodopalladium complexes. [(PS,3R,4R,P′S)1-(t-butoxycarbonyl)-3,4-bis[(2-cyanoethyl)phenylphosphino]pyrrolidine-P,P′]diiodopalladium(II) (14-1) was characterised by X-ray crystallography.     

Analogues of DIOP. Synthesis, reactivity, and NMR behaviour

The (4R,5R)-4,5-Bis(diphenylphosphinomethyl)-2-(-naphthoxy)-1,3,2-dioxaphospholane (1) and (4R,5R)-4,5-bis(diphenylphosphinomethyl)-2-dimethylamino-2-oxo-1,3,2-dioxaphospholane (2), analogues of the chiral bisphosphine ligand DIOP, have been synthesized. Both compounds have a second phosphorus functionality in the backbone of the chiral bisphosphine. That the reactivities of the various phosphorus atoms in 1 are different was shown for the reaction with BH₃. The complexation behaviour of 1 towards Rh^I was studied with the aid of ³¹P NMR spectroscope.     

Synthesis and mesomorphic properties of chiral swallow-tailed thioester liquid crystals with lateral substituents

Two homologous series of chiral swallow-tailed thioester materials, 1-ethylpropyl (R)-2-[3-fluoro-4-(4'-alkyloxybiphenylcarbonylthio)phenoxy]propionates, I-6 (m = 8-12), and 1-ethylpropyl (R)-2-[3-methyl-4-(4'-alkyloxybiphenylcarbonylthio)phenoxy]propionates, II-6 (m = 8-12), have been synthesized and their mesomorphic phases studied. The results show that materials I-6 (m = 8-12) with a fluoro substituent, display the phase sequence I-BPII-N*-SmC*-Cr, whereas materials II-6 (m = 8-12) with a methyl substituent display the phase sequence I-N*-TGBA*-SmA*-Cr during cooling. The physical properties of the SmC* phase in materials I-6 were measured. The results show that the maximum P _s values are in the range 91-95 nC cm^-2 and the maximum tilt angles are about 34-37°.