Stereoselectivity in Reactions of Metal Complexes. Part XV. Structure and stability of chiral cobalt(III) complexes with pentadentate ligands

The syntheses and characterization of four new linear pentadentate ligands and their Co^III complexes are described: N,N′-[(pyridine-2,6-diy)bis(methylene)]bis[sarcosine] (sarmp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[(R)- or (S)-proline] ((R,R)- or (S,S)-promp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[N-(methyl)-(R)- or (S)-alanine] ((R,R)- or (S,S)-malmp); 2,2′-[pyridine-2,6-diyl]bis[(S)- or rac-N-(acetic acid)pyrrolidine] ((S,S)- or rac-bapap). The complexes were characterized and, with but one exception, complex formation is stereospecific: Δ-exo-(R,R) (or Λ-exo-(S,S)) for promp and Λ-(R,R) (or Δ-(S,S)) for bapap. The exception is [Co((R,R)- or (S,S)-malmp)H₂O]ClO₄ for which two forms are obtained, to which Λ-endo-(R,R) (or Δ-endo-(S,S)) and, tentatively, Δ-unsymmetric-(R,R)- (or Λ-unsymmetric-(S,S)-) configurations are assigned. X-Ray crystal structures are presented for the complexes [Co(sarmp)H₂O]ClO₄, [Co((S,S)-promp)H₂O]ClO₄, [Co(rac-bapap)H₂O]ClO₄ and endo-[Co(rac-malmp)H₂O]ClO₄. Ligand acid dissociation and Co^II and Fe^II complex-formation constants are reported.     

C45- and C50-Carotinoide. 1. Mitteilung. Synthese von (R)- and (S)-Lavandulol

C₄₅- and C₅₀-Carotenoids, 1st Communication. Synthesis of (R)- and (S)-Lavandulol Starting with methyl (3 R)-3-hydroxybutanoate ((R)-7) and ethyl (3 S)-3- hydroxybutanoate ((S)- 11 ), respectively, (R)- and (S)-lavandulol ((R)- 1 and (S)- 1 ) were synthesized with high optical purity. The synthesized key intermediates (R)- 6 and (S)- 6 are suitable compounds for the synthesis of optically active acyclic C₄₅- and C₅₀-carotenoids.     

Arylacetic acid derivatization of 2,3- and internal erythro-squalene diols. Separation and absolute configuration determination

We have studied a new approach for the resolution and absolute configuration determination of the enantiomers of squalene diols as intermediate precursors in the chemical synthesis of different squalene oxides (SOs); (3R)- and (3S)-2,3-SO, (6R,7R)- and (6S,7S)-6,7-SO, and (10R,11R)- and (10S,11S)-10,11-SO. Monoderivatization of the corresponding racemic squalene diol intermediates with pure stereoisomers of (S)-(+)-methoxyphenyl acetic acid ((S)-(+)-MPA), (S)-(+)-9-anthrylmethoxyacetic acid ((S)-(+)-9-AMA) and (S)-(+)-acetoxyphenylacetic acid ((S)-(+)-APA) afforded the diastereomeric esters which could be easily separated by column flash chromatography with silica gel. In addition, the absolute configuration for these diastereoisomers of the derivatized diols was advantageously inferred from ¹H NMR data according to the models depicted for these derivatizing chiral agents. In order to demonstrate the absolute configuration assignment of the different stereoisomers, (S)-(+)-AMA showed the larger Δδ by ¹H NMR, however, (S)-(+)-MPA esters were much more stable derivatives.     

Synthèse des (−)-(6R)-et(+)-(6S)-tétrahydro-6-[(Z)-pent-2-ényl]-2H-pyran-2-one,lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L.

Synthesis of (?)-(6R)- and (+)-(6S)-Tetrahydro-6-[(Z)-pent-2-enyl]-2H-Pyran-2-one, lactones from Jasminum grandiflorum L. and from Polianthes tuberosa L. (?)-(2S)-Ethyl 2-hydroxyhexanedioate ((2S)- 2 ) was obtained by kinetic resolution of racemic ethyl 2-hydroxy-hexanedioate with baker's yeast. The key intermediates (+)-(5R)- and (?)-(5S)-ethyl 5,6-epoxyhexanoate ((5R)- and (5S)- 6 , resp.) are proved to be useful synthons for the total synthesis of chiral 6-alkyl-δ-lactones, as exemplified by the preparation of both enantiomers of jasmine lactone ((6R)- and (6S)- 10 , resp.).     

Chiral Tetraamines Based on (S)-2-(Aminomethyl)pyrrolidine: Template synthesis and properties of copper(II) complexes

The template reaction of {bis[(S)-2-(aminomethyl)pyrrolidine]}copper(II) with formaldehyde, nitroethane, and base in MeOH yields optically pure {1,7-bis[(S)-pyrrolidin-2-yl]-4-methyl-4-nitro-2,6-diazaheptane}- copper(II) ([Cu((S,S)-mnppm)]²⁺) in high yield. The same reaction with rac-2-(aminomethyl)pyrrolidine is also described. Preparative details and spectroscopic and electrochemical properties of the Cu^II complexes and of the free ligands are reported and compared with structural, spectroscopic and electrochemical data of the Cu^II complex of the unsubstituted parent ligand 1,7-bis[(S)-pyrrolidin-2-yl]-2,6-diazaheptane (ppm). The crystal structure of [Cu(ppm)]Cl ClO₄ has been determined by X-ray diffraction methods.     

Efficient Synthesis of Enantiomerically Pure α-Ionone from (R)- and (S)-α-Damascone

(R)- and (S)-α-ionone ((R)- and (S)- 1 , resp.) were prepared from (R)- and (S)-α-damascone ((R)- and (S)- 3 , resp.) without racemization in 48% yield employing a new enone transposition. The described transposition is complementary to existing methods whose application is often prohibited by the structural requirements of the substrate. The now easily accessible α-ionones of desired absolute configuration are useful as chiral building blocks for terpenoid synthesis.     

An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.     

Axially Dissymmetric Bis(triaryl)phosphines in the Biphenyl series: Synthesis of (6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine) (‘BIPHEMP’) and analogues,and their use in Rh(I)-catalyzed asymmetric isomerizations of N,N-diethylnerylamine

The axially dissymmetric diphosphines (?)-(R)- and (+)-(S)-(6-6′-dimethylbiphenyl-2,2′-diyl)bis(diphenyl-phosphine) ((?)-(R)- 10 and (+)-(S)- 10 ; ‘BIPHEMP’) have been synthesized, starting from (R)- and (S)-6,6′-dimethylbiphenyl-2,2′-diamine ((R)- and(S)- 16 ), respectively, via Sandmeyer reaction, liathiation, and phosphinylation. Moreover, racemic 4,4′- dimethyl- and 4,4′-bis(dimethylamino)-substituted analogues 11 and 12 respectively, and the 6,6′-bridged analogues 1,11-bis(diphenylphosphino)-5,7-dihydrodibenz[c,e]oxepin (13) were synthesized and resolved into optically pure (R)- and(S)-enantiomers via complexation with di-μ-chlorob is {(R)-2-[1-(dimethylamino)ethyl]pheny-C? N}dipalladium(II) ((R)- 18 ). The molecular structures of the diphosphines (S)- 10 and (R)- 13 and of two derived cationic Rh(I) complexes,[Rh((S)- 10 )(nbd)]BF₄ and [Rh((R)- 13 )(nbd)]BF 4 were determined by x-ray analyses. Absolute configurations were established for (+)-(S)- 10 by X-ray analyses of both the free diphosphine and of the derived Rh(I) complex, and for (?)-(R)- 13 by X-ray analysis of the derived Rh(I) complex. Configurational assignments for the substituted BIPHEMP analogues 11 12 were achieved by means of ¹H-NMR comparisons. The BIPHEMP ligand 10 and analogues 11 , 12 and 13 are the first examples of optically active bis(triaylphosphines) containing the axially dissymmetric biphenyl moiety. All these new diphosphines proved to be excellent asymmetry-inducing ligands in Rh(I)-catalyzed isomerizations of N,N-diethylnerylamine affording citronellat enamine of 98-99% ee.     

1,2-Epoxycarotinoide 5. Mitteilung,Synthese von (S)-1,2-Epoxy-1,2,7,8,7′,8′-hexahydro-Ψ, Ψ-carotin ((S)-1,2-Epoxy-1,2-dihydro-ζ-carotin)

1,2-Epoxycarotenoids, Synthesis of (S)-1,2-Epoxy-1,7,8,7′,8′-hexahydro-Ψ, Ψ-carotene ((S)-1,2-Epoxy-1,2-dihydro-ζ-carotene) The synthesis of (S)-1,2-Epoxy-1,2-dihydro-ζ-carotene ((all-E,S)- 1 ) using (E,E)-farnesol (3) as starting material, and a Sharpless epoxidation as key step is described.     

C45- und C50-Carotinoide. 3. Mitteilung. Synthese von (S)-Trisanhydrobacterioruberin

C₄₅-and C₅₀-Carotenoids: Synthesis of (S)-Trisanhydrobacterioruberin The Synthesis of (S)-trisanhydrobacterioruberin ((S)- 1 ) is reported.     

Le (−)-(2S)-2-Hydroxyhexanedioate de diéthyle,nouveau bloc chiral pour la synthèse énantiospécifique

The (?)-(2S)-Diethyl 2-Hydroxyhexanedioate, a New Chiral Building Block for Enantioselective Synthesis (?)-(2S)-Diethyl 2-hydroxyhexanedioate ((2S)-3) has been obtained by enantioselective reduction of diethyl 2-oxohexanedioate ( 1 ) with baker's yeast. The key intermediate (?)-(5S)-ethyl 5,6-dihydroxyhexanoate ((5S)- 5 ) is proved to be a useful synthon for the synthesis of chiral δ-lactones and a precursor of leukotriene LTB₄ ((5S)- 13 ).     

SYNTHESIS OF (S,S)-BIS(4-ALKYLOXAZOLIN-2-YL-METHYL)-1,5-DIAZACYCLOOCTANE

ABSTRACT

Synthesis of a series of new chiral tetradentate ligands ((S,S)-1,5-bis(4-alkyloxazolin-2-yl-methyl)-1,5-diazacyclooctane) is described.     

Synthesis of (R)- and (S)-5-(Hydroxymethyl)-3-isopropyloxazolidin-2-one,intermediates in the preparation of optically active β-blockers

The (R)- and (S)-5-(hydroxymethyl)-3-isopropyloxazolidin-2-ones, ((R)- and (S)- 2 , resp.), pivotal intermediates in the preparation of optically active β-blockers, were synthesized using (R,E)-2-hydroxypent-3-enenitrile ( 1 ) as the chiral starting material. In the synthesis of (R)- 2 , a known cyclization/inversion step was applied.     

Stereoselective Formation of Ternary Copper(II) Complexes of (S)-Amino-acid Amides and (R)- or (S)-Histidine and (R)- or (S)-Tyrosine in Aqueous Solution

Formation constants of ternary complexes of Cu^II with (S)-amino-acid amides ((S)-phenylalaninamide, (S)-prolinamide, and (S)-tryptophanamide) and (R)- or (S)-histidine and (R)- or (S)-tyrosine were determined potentiometrically in aqueous solution. Significant stereoselectivity was presented by all three amides towards histidine, the diastereoisomeric complexes with ‘heterochiral’ ligands being more stable than those with ‘homochiral’ ligands (see Table 3). The stereoselectivity observed with (S)-phenylalaninamide and (S)-tryptophanamide may be explained on the basis of hydrophobic stacking interactions between 1H-imidazole and the aromatic side chain, favoured by the terdentate behaviour of histidine (see Fig.2), whereas repulsive effects seem to be prevalent with (S)-prolinamide. Only (S)-prolinamide and (S)-phenylalaninamide show appreciable stereoselectivity with tyrosine, which is bidentate, probably on account of repulsive interactions. The present results on the stability of ternary complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination performed by Cu^II complexes of (S)-amino-acid amides added to the mobile phase in HPLC (reversed phase).     

C45- and C50-Carotehoids. Part 8. Synthesis of (all-E,2S,2′S)-bacterioruberin, (all-E,2S,2′S)-monoanhydrobacterioruberin, (all-E,2S,2′S)-bisanhydrobacterioruberin, (all- E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydro- bacterioruberin,and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin

Starting from (R)-3-hydroxybutyric acid ((R)- 10 ) the C₄₅- and C₅₀-carotenoids (all-E,2S,2′S)-bacterioruberm ( 1 ), (all-E,2S,2′S)-monoanhydrobacterioruberin ( 2 ), (all-E,2S,2′S)-bisanhydrobacterioruberin ( 3 ), (all-E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydrobacterioruberin ( 5 ), and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin ( 6 ) were synthesized. By comparison of the chiroptical data of the natural and the synthetic compounds, the (2S)- and (2′S)-configuration of the natural products 1–3 and 6 was established.     

Highly stereoselective asymmetric aldol routes to tert-butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building blocks for novel protease inhibitors

Enantioselective syntheses of tert-butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate and ((S)-2-(3,5-difluorophenyl)-1-((R)-oxiran-2-yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti-aldol reactions to set both stereogenic centers. We investigated ester-derived Ti-enolate aldol reactions as well as Evans’ diastereoselective syn-aldol reaction for these syntheses. We have converted optically active ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate to a potent β-secretase inhibitor.     

Syntheses of the Enantiomers of γ-Cyclogeranic Acid, γ-Cyclocitral,and γ-Damascone: Enantioselective protonation of enolates

(R)-and (S)-γ-cyclogeranic acid ((R)-and (S)- 9 , resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)- 9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)- 6 , resp.), and (R)-and (S)-γ-damascone ((R)-and (S)- 5 , resp.). A more direct entry to (R)-and (S)- 9 consisted in the enantioselective protonation of a thiol ester enolate with (?)- or (γ)-N-isopropylephedrine((?)- or (γ)- 20 ) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)- 24 , resp.; 97% ee). The esters (R)- and (S)- 24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)- 5 , resp.). Alternatively, (S)- 5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (?)-N-isopropylephedrine ((?)- 20 ). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.     

Trennung und absolute Konfiguration der C(8)-epimeren (all-E)-Neochrome (Trollichrome) und -Dinochrome

Separation and Absolute Configuration of the C(8)-Epimeric (app-E)-Neochromes (Trollichromes) and -Dinochromes The C(8′)-epimers of (all-E)-neochrome were separated by HPLC and carefully characterized. The faster eluted isomer, m.p. 197.8–198.3°, is shown to have structure 3 ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-dodehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). To the other isomer, m.p. 195-195.5°, we assign structure 6 , ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-didehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). The already known epimeric dinochromes (= 3-O-acetylneochromes) can now be formulated as 4 and 5 , (‘epimer 1’ and its trimethylsilyl ether) and 7 and 8 , (‘epimer 2’ and its trimethylsilyl ether), respectively.     

Axially Dissymmetric Diphosphines in the Biphenyl Series: Synthesis of (6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine)(‘MeO-BIPHEP’) and Analogues via an ortho-Lithiation/Iodination Ullmann-Reaction Approach

The new axially dissymmetric diphosphines (R)- and (S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenyl phosphine) ((R)- and (S)- 5a ; ‘MeO-BIPHEP’) and the analogues (R)- and (S)- 5b and 5c have been synthesized in enantiomerically pure form. These ligands have become readily available by a synthetic scheme which employs, as key steps, an ortho-lithiation/iodination reaction of the (m-methoxyphenyl)diprienylphosphine oxides 8 and a subsequent Ullmann reaction of the resulting iodides 9 to provide the racemic bis(phosphine oxides) 10 . The bis(phosphine oxides) 10 subsequently are resolved with (?)-(2R,3R)- and (+)-(2S,3S)-O-2,3-dibenzoyltartaric acid and reduced to diphosphines 5 . The Ullmann reaction constitutes a new and efficient route to 2,2′-bis(phosphinoyl)-substituted biphenyl systems. Absolute configurations were established for (R)- 5a by X-ray analysis of the derived Pd complex (R,R)- 17a , and for 5b and 5c by means of ¹H-NMR comparisons of the derived Pd complexes 16 or 17 , respectively, and by means of CD comparisons. The MeO-BIPHEP diphosphine 5a proved to be as efficient as the previously described BIPHEMP diphosphine ((6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine)) in enantioselective isomerizations and hydrogenations.     

Synthese und Strukturaufklärung von Merucathinon und Synthese von Cathinon. Inhaltsstoffe von Catha edulis FORSK

Synthesis and Structure Elucidation of Merucathinone and Synthesis of Cathinone. Constituents of Catha edulis FORSK . Starting from L-alanine, two constituents of Catha edulis FORSK ., (S)-4-amino-1-phenylpent-1-en-3-on ((S)- 3 ; merucathinone) and (S)-2-amino-1-phenylpropan-1-on ((S)- 1 ; cathinone) were synthesized.