Circulardichroismus. 62. Mitteilung. Chiroptische Eigenschaften einiger Trimethylcyclohexen-Derivate: Die Jonone,Irone und Abszisinsäuren

The absolute configuration of (+)-α-ionone 3 (R), the absolute configurations at C(6) of (+)-cis-α-irone 5 (6S) and (?)-trans-α-irone 6 (6R), and the absolute configurations of (+)-cis-abscisic acid 10 (S) and (+)-trans-abscisic acid 11 (S) are deduced from the CD.-spectra.     

Stereospecific syntheses of all four stereoisomers of 4-fluoroglutamic acid

(+)- -threo-4-Fluoroglutamic acid [(+)-(2S, 4S)-fluoroglutamic acid] has been synthesizedstarting with the natural (−)-4-trans-hydroxy- -proline. Its acetylation at nitrogen followedby esterification with diazomethane afforded methyl 1-acetyl-trans-4-hydroxy- -prolinatewhich was converted to methyl 1-acetyl-cis-4-fluoro- -prolinate by means of diethylaminosulfurtrifluoride (DAST) or 2-chloro-1,1,2-trifluorotriethylamine. The mixture wasoxidized by ruthenium tetroxide to methyl 1-acetyl-cis-4-fluoro- -pyrrolidin-5-one-2-carboxylate,whose acid hydrolysis yielded the title compound. A similar sequence of reactionsconverted cis-4-hydroxy- -proline to (−)- -erythro-4-fluoroglutamic acid [(−)(2R, 4S)-fluoroglutamic acid]. (−)- -threo-4-Fluoroglutamic acid [(−)-(2R, 4R)-floroglutamicacid] was prepared analogously from trans-4-hydroxy- -proline, obtained from its diastereomerby inversion of configuration at carbon 4 of the pyrrolidine ring using thediethyl azodicarboxylate-triphenylphosphine procedure. cis-4-Hydroxy- -proline, necessaryfor the synthesis of (+)- -erythro-4-fluoroglutamic acid [(+)-(2S, 4R)-fluoroglutamicacid], was prepared from trans-4-hydroxy- -proline by benzyloxycarbonylation at thenitrogen, oxidation of the 1-benzyloxycarbonyl-trans-4-hydroxy- -proline to 1-benzyloxy-carbonyl-4-oxo- -proline, its reduction to 1-benzyloxycarbonyl-cis-4-hydroxy- -proline anddeprotection of the latter at the nitrogen. (−)-cis-4-Fluoro- -proline and (+)-trans-4-fluoro- -proline were isolated after the hydrolysis of incompletely oxidized methyl 1-acetyl-cis-4-fluoro- -prolinate and methyl 1-acetyl-trans-4-fluoro- -prolinate, respectively.     

Synthesis of(+)-(2S, 6S)-trans-α-Irone and of(-)-(2S, 6S)-trans-γ-Irone

A 3:1 mixture of (+)-(2S, 6S)-trans-α-irone ((+)-1) and (?)-(2S, 6S)-trans-γ-irone (?)-2) has been synthesized with ca. 70% e. e. by the ene reaction of (?)-(S)-3 and but-3-yn-2-one.     

Enzyme-Mediated Preparation of (+)- and (–)-cis-α-Irone and (+)- and (–)-trans-α-Irone

The preparation of (−)- and (+)-trans-α-irone ( 1a and 1b , resp.) and of (+)- and (−)-cis-α-irone ( 1c and 1d , resp.) from commercially available Irone alpha ^® is reported. The relevant step in the synthetic sequence is the initial chromatographic separation of crystalline (±)-4,5-epoxy-4,5-dihydro-cis-α-irone ((±)- 5 ) from oily (±)-4,5-epoxy-4,5-dihydro-trans-α-irone ((±)- 4 ). The latter was subsequently converted, after NaBH₄ reduction, into the crystalline 3,5-dinitrobenzoate ester (±)- 8 , thus allowing a complete separation of the two corresponding diastereoisomeric alcohol derivatives. Suitable enantiomerically pure precursors of the desired products 1a – d were obtained by kinetic resolution of the racemic allylic alcohols derived from (±)- 5 and (±)- 8 , mediated by lipase PS (Amano). The last steps consisted of MnO₂ oxidation and removal of the epoxy moiety with Me₃SiCl/NaI in MeCN. External panel olfactory evaluation showed that (−)-cis-α-irone ( 1d ) has the finest and most distinct `orris butter' character.     

Preparation and Absolute Configuration of Some Iris Essential Oil Constituents of the 5-methylsafranic-acid series

The β-dienoate (+)-(5S)- 13a (86% ee; meaning of α and β as in α- and β-irone, resp.) was obtained from (?)-(5S)- 9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)- 15 /(+)-(1R,5S)- 15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the α-isomer (?)-(R)- 16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl₄-catalyzed stereospecific cyclization of (+)-(Z)- 6 to (?)-trans- 8a (Scheme 2), followed by a diastereoselective epoxidation to (+)- 11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (?)- 12 , the same ester (+)- 13a (Scheme 3), but with poor optical purity (13% ee), due to an initial rapid [1,2]-H shift. The absolute configuration of (?)- 16a–c was confirmed by chemical correlation with (?)-trans- 19 (Scheme 4). ¹³C-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.     

Chemo‐Enzymatic Synthesis and Determination of the Absolute Configuration of Both Enantiomers of Methyl trans‐5‐Oxo‐2‐pentylpyrrolidine‐3‐carboxylate Precursors of the Aza Analogues of (+)‐ and (−)‐Methylenolactocin

Enantiomerically pure methyl esters of (+)‐(2R,3S)‐ and (−)‐(2S,3R)‐5‐oxo‐2‐pentylpyrrolidine‐3‐carboxylic acid with 99% and 98% ee were obtained by enzymatic resolution of the corresponding racemic mixture using α‐chymotrypsin and pig‐liver acetone powder, respectively. Their absolute configurations were established by chemical methods, i.e., conversion of the trans‐γ‐lactam moiety to the corresponding γ‐lactone of known configuration. The favorable interactions between the trans‐γ‐lactam and α‐chymotrypsin were rationalized by molecular‐mechanics calculations, which suggest a different situation for the cis‐diastereoisomer.     

Stereochemical Analysis of an Aromatic Triplet Di-π-methane Rearrangement

It is shown that (−)-(S)-N,N-dimethyl-2-(1′-methylallyl)aniline ((−)-(S)- 4 ), on direct irradiation in MeCN at 20°, undergoes in its lowest-lying triplet state an aromatic di-π-methane (ADPM) rearrangement to yield (−)-(1′R,2′R)- and (+)-(1′R,2′S)-N,N-dimethyl-2-(2-methylcyclopropyl)aniline ((−)-trans- and (+)-cis- 7 ) in an initial trans/cis ratio of 4.71 ± 0.14 and in optical yields of 28.8 ± 5.2% and 15 ± 5%, respectively. The ADPM rearrangement of (−)-(S)- 4 to the trans- and cis-configurated products occurs with a preponderance of the path leading to retention of configuration at the pivot atom (C(1′) in the reactant and C(2′) in the products) for (−)-trans- 7 and to inversion of configuration for (+)-cis- 7 , respectively. The results can be rationalized by assuming reaction paths which involve the occurrence of discrete 1,4- and 1,3-diradicals (cf. Schemes 10, 12, and 13). A general analysis of such ADPM rearrangements which allows the classification of these photochemical reactions in terms of borderline cases is presented (Scheme 14). It is found that the optical yields in these ‘step-by-step’ rearrangements are determined by the first step, i.e. by the disrotatory bond formation between C(2) of the aromatic moiety and C(2′) of the allylic side chain leading to the generation of the 1,4-diradicals. Moderation of the optical yields can occur in the ring closure of the 1,3-diradicals to the final products, which may take place with different trans/cis-ratios for the individual 1,3-diradicals. Compounds (−)-trans- 7 as well as (+)-cis- 7 easily undergo the well-known photochemical trans/cis-isomerization. It mainly leads to racemization. However, a small part of the molecules shows trans/cis-isomerization with inversion of configuration at C(1′), which is best explained by a photochemical cleavage of the C(1′)–C(3′) bond.     

Photochemische Umsetzung von optisch aktiven 2-(1′-Methylallyl)anilinen mit Methanol

Photochemical Reaction of Optically Active 2-(1′-Methylallyl)anilines with Methanol It is shown that (?)-(S)-2-(1′-methylallyl)aniline ((?)-(S)- 4 ) on irradiation in methanol yields (?)-(2S, 3R)-2, 3-dimethylindoline ((?)-trans- 8 ), (?)-(1′R, 2′R)-2-(2′-methoxy-1′-methylpropyl)aniline ((?)-erythro- 9 ) as well as racemic (1′RS, 2′SR)-2-(2′-methoxy-1′-methylpropyl) aniline ((±)-threo- 9 ) in 27.1, 36.4 and 15.7% yield, respectively (see Scheme 3). By deamination and chemical correlation with (+)-(2R, 3R)-3-phenyl-2-butanol ((+)-erythro- 13 ; see Scheme 4) it was found that (?)-erythro- 9 has the same absolute configuration and optical purity as the starting material (?)-(S)- 4 . Comparable results are obtained when (?)-(S)-N-methyl-2-(1′-methylallyl)aniline ((?)-(S)- 7 ) is irradiated in methanol, i.e. the optically active indoline (+)-trans- 10 and the methanol addition product (?)-erythro- 11 along with its racemic threo-isomer are formed (cf. Scheme 3). These findings demonstrate that the methanol addition products arise from stereospecific, methanol-induced ring opening of intermediate, chiral trans, -(→(?)-erythro-compounds) and achiral cis-spiro [2.5]octa-4,6-dien-8-imines (→(±)-threo-compounds; see Schemes 1 and 2).     

An Alternative Access to (±)-α-Irones and (±)-β-Irone via Acid-Mediated Cyclisation

Acid-mediated cyclisation of trienone 8 , readily available from 2,3-dimethylbutanal ( 1 ; five steps: 47% yield), using fluorosulfonic acid (6.8 mol-equiv.) in 2-nitropropane at ?70°, afforded a 14:9:1 mixture (70% yield) of (±)-cis-α-irone ( 9 ), (±)-trans-α-irone ( 10 ), and (±)-β-irone ( 11 ). Other acidic conditions examined, using 95% aq. H₂SO₄ solution, 85% aq. H₃PO₄ solution, or SnCl₄, gave inferior results.     

235. Information on the sesquiterpenoid C 12 -Ketones from the essential oil of Vetiveria zizanioides (L.) Nash

Two new C₁₂-ketones, (+)-(1S, 10R)-1,10-dimethylbicyclo[4.4.0]dec-6-en-3-one ( 5 ) and (+)-(6S, 10S)-6,10-dimethylbicyclo[4.4.0]dec-1-en-3-one ( 6 ), have been isolated from Reunion vetiver oil (Vetiveria zizanioides (L.) Nash). Structure and absolute configuration of 5 were established by a four-step synthesis from (+)-isonootkatone ((+)-α-vetivone) ( 1 ). The structure of 6 followed from its spectroscopic properties and was confirmed by direct comparison with an authentic racemic sample. The absolute configuration of 6 was established by chemical correlation with (+)-α-eudesmol ( 13 ).     

Preparation and Absolute Configuration of (−)-(E)-α-trans-Bergamotenone

The synthesis, absolute configuration, and olfactive evaluation of (?)-(E)-α-trans-bergamotenone (= (?)-(1′S,6′R,E)-5-(2′,6′-dimethylbicyclo[3.1.1]hept-2′-en-6′-yl)pent-3-en-2-one; (?)- 1 ), as well as its homologue (?)- 19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (?)-α-trans-bergamotene (= (?)-(1 S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1. 1]hept-2-ene; (?)- 2 ), together with those of the structurally related aldehydes (?)- 3a,b and alcohols (?)- 4a,b , have been rigorously assigned.     

Polymerization of optically active 2-fluorophenyl-4-fluorophenyl-2-pyridylmethyl methacrylate with anionic and radical initiators: Stereospecificity and helix-sense selection

Almost optically pure (+)- and (−)-2-fluorophenyl-4-fluorophenyl-2-pyridylmethyl methacrylate (2F4F2PyMA) monomers were obtained by HPLC resolution of the racemic monomer and polymerized with the use of anionic and free-radical initiators. Helix-sense selectivity during the polymerization seemed to be governed mainly by the chirality of the monomer itself, and the polymers obtained by using the complex of N,N′-diphenylethylenediamine monolithium amide with (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (PMP) in toluene at −78°C appeared to possess single-handed helical conformation (+)-poly[(−)-2F4F2PyMA], [α]₃₆₅ + 1510°; (−)-poly[(+)-2F4F2PyMA], [α]₃₆₅ − 1610°]. The single-handed helical (+)-poly[(−)-2F4F2PyMA] and (−)-poly[(+)-2F4F2PyMA] obtained with the PMP complex exhibited better chiral recognition ability toward trans-stilbene oxide compared with the single-handed helical poly(rac-2F4F2PyMA) prepared previously. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2645–2648, 1999     

Die absolute Konfiguration der 3,5-Diaminohexansäure aus der β-Lysin-Mutase-Reaktion

Absolute configuration of the 3,5-diaminohexanoic acid produced in the β-lysine mutase reaction The (3S, 5S)-configuration of the 3,5-diaminohexanoic acid 3 produced by the coenzyme-B₁₂-dependent β-lysine mutase from Clostridium sticklandii has been determined by two different methods: by comparison of the ¹H-NMR.-spectrum of its δ-lactam with that of synthetic (±)-cis-and (±)-trans-4-amino-6-methyl-piperidones ( 1 and 2 ) and by chemical correlation with (+)-(6S)-6-methyl-piperidone-2 ( 9 ).     

Synthese und Chiralität der stereoisomeren Achillene,Achillenole und Hymentherene

(+)-cis-Achillene ( 10 ) and (?)-trans-achillenol (7), two monoterpenes recently isolated [1] from the essential oil of Achilleafilipendulina, were synthesized, together with their stereoisomers (?)-(9) and (+)-(8), starting from (S)-(+)-2,6-trans-dimethylocta-1,3, 7-triene ( 1 ). The isomeric ß-hymen thereties ((?)- 3 and (+)-4), often quoted [2] [3] [4] but never isolated, were obtained as intermediates. The mode of synthesis chosen establishesis (R)-chirality for naturally occurring (?)-trans-achillenol (7) and (+)-cis-achillene ( 10 ) as well as for the purely synthetic 4, 7-diene derivatives described in this paper.     

Konstitution und absolute Konfiguration der Rhoeadin-Alkaloide (+)-Alpinigenin und (+)-cis-Alpinigenin

The constitution and absolute configuration of the rhoeadine alkaloids (+)-alpinigenine and (+)-cis-alpinigenine. The fundamental structure of the hemi-acetal phenylbenzazepine alkaloid (+)-alpinigenine ( 1 ), isolated from Papaver bracteatum LINDL ., was derived essentially from ¹H-NMR.- and mass-spectra of 1 and its derivatives 7, 10 and 14 (cf. Scheme 2). The positioning of the four methoxy groups in the two aromatic rings could be deduced from the ¹H-NMR.-spectra of the N-oxides 14 and 15 in which, as a result of favourable sterical and conformational behaviour, an interaction exists between the N-oxide oxygen atom and one of the two ortho protons in ring C. The B/D-trans-fused 1 undergoes isomerization in 1N HCl to cis-alpinigenine ( 16 ). A stereochemical correlation between bases in the trans-and cis-series was enabled via an Emde degradation of the corresponding methylacetal-methyliodides 21 resp. 19 leading to the enantiomeric isochroman derivatives 22 resp. 23 which are achiral at C (2) (Scheme 4). The configuration at C (14) in the hemi-acetals (eg. 1 and 16 ) and the methyl ethers (eg. 7 and 8 ) is discussed in detail (cf. Scheme 7). (+)-Alpinigenine ( 1 ) has the (1S, 2R, 14R) configuration and (+)-cis-alpinigenine ( 16 ), in chloroform or acetone solution, the (1R, 2R, 14R) configuration.     

Synthesis and transformations of (±)-trans-4aβ(H), saα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one

Hydrogenation of 4,7-dimethylcoumarin ( 1 ) in alkaline medium has been shown to furnish a mixture of (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one ( 2 ), (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 3 ) and (±)-cis-4aα(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 4 ) in 40:25:35:ratio, respectively. The stereochemistry of the major hydrogenation product 2 , has been established by transforming it to p-menthane derivatives e.g. (±)-2 (R)-[2′(R)hydroxy-4′(R) methylcyclohex-(1′S)-yl]propan-1-ol ( 20 ) and (±)-trans-3α,6β-dimethyl-3aβ(H),7aα(H)-octahydrobenzofuran ( 12 ). Starting from a mixture of lactones 2, 3 and 4 , lactone 3 has been obtained in pure state employing a sequence of reactions.     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.     

Neue Phellandren-Derivate aus dem Wurzelöl von Angelica archangelicaL

New Phellandrene Derivatives from the Root Oil of Angelica archangelica L . 2-Nitro-1,5-p-menthadiene ( 5 ), trans- and cis-6-nitro-1(7), 2-p-menthadiene ( 6 and 7 ), trans-1(7), 5-p-menthadien-2-yl acetate ( 9 ) and a formal phellandrene derivative, 7-isopropyl-5-methyl-5-bicyclo [2.2.2]octen-2-one ( 16 ), have been identified in the root oil of Angelica archangelica L . Starting from (?)-(R)-α-phellandrene ( 1 ) (R)- 5 , (4R, 6S)- 6 /(4R, 6R)- 7 , (2S, 4R)- 9 and (1R, 4R, 7R)- 16 as well as (2S, 4R)- 11 , (2R, 4R)- 12 and (2R, 4R)- 10 have been prepared.     

Synthesis and Absolute Configuration of Naturally Occurring Dactyloxene-B and -C

Natural (+)-dactyloxene-B (12) and -C (13) have been synthesized starting from (+)-trans-2, 5, 6-trimethyl-l-cyclohexene-l-carbaldehyde (1) which is shown to have the (5S, 6R)-configuration by chemical correlation with (+)-(2R, 3S, 6S)-2, 3, 6-trimethylcyclohexanone. The absolute configurations are therefore (2R, 5R, 9S, 10R) for (+)-dactyloxene-B and (2R, 5S, 9S, 10R) for (+)-dactyloxene-C.     

Synthesis of thienamycin-like 2-iso-oxacephems with optional stereochemistry

All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (αR,6R,7R)- and (αS,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from l- and d-threonine, the configuration at the α-position was inverted by using Mitsunobu reactions providing the (αS,6R,7R)- and (αR,6S,7S)-diastereomers of the compounds above. A synthetic route to the cis-annelated analogues was also worked out.