Das Carotinoidspektrum der Hagebutten von Rosa pomifera: Nachweis von (5Z)-Neurosporin; Synthese von (3R, 15Z)-Rubixanthin

Carotenoids from Hips of Rosa pomifera: Discovery of (5Z)-Neurosporene; Synthesis of (3R, 15Z)-Rubixanthin Extensive chromatographic separations of the mixture of carotenoids from ripe hips of R. pomifera have led to the identification of 43 individual compounds, namely (Scheme 2): (15 Z)-phytoene (1) , (15 Z)-phytofluene (2) , all-(E)-phytofluene (2a) , ξ-carotene (3) , two mono-(Z)-ξ-carotenes ( 3a and 3b ), (6 R)-?, ψ-carotene (4) , a mono-(Z)-?, ψ-carotene (4a) , β, ψ-carotene (5) , a mono-(Z)-β, ψ-carotene (5a) , neurosporene (6) , (5 Z)-neurosporene (6a) , a mono-(Z)-neurosporene (6b) , lycopene (7) , five (Z)-lycopenes (7a–7e) , β, β-carotene (8) , two mono-(Z)-β, β-carotenes (probably (9 Z)-β, β-carotene (8a) and (13 Z)-β, β-carotene (8b) ), β-cryptoxanthin (9) , three (Z)-β-cryptoxanthins (9a–9c) , rubixanthin (10) , (5′ Z)-rubixanthin (=gazaniaxanthin; 10a ), (9′ Z)-rubixanthin (10b) , (13′ Z)- and (13 Z)-rubixanthin (10c and 10d , resp.), (5′ Z, 13′ Z)- or (5′ Z, 13 Z)-rubixanthin (10e) , lutein (11) , zeaxanthin (12) , (13 Z)-zeaxanthin (12b) , a mono-(Z)-zeaxanthin (probably (9 Z)-zeaxanthin (12a) ), (8 R)-mutatoxanthin (13) , (8 S)-mutatoxanthin (14) , neoxanthin (15) , (8′ R)-neochrome (16) , (8′ S)-neochrome (17) , a tetrahydroxycarotenoid (18?) , a tetrahydroxy-epoxy-carotenoid (19?) , and a trihydroxycarotenoid of unknown structure. Rubixanthin (10) and (5′ Z)-rubixanthin (10a) can easily be distinguished by HPLC. separation and CD. spectra at low temperature. The synthesis of (3 R, 15 Z)-rubixanthin (29) is described. The isolation of (5 Z)-neurosporene (6a) supports the hypothesis that the ?-end group arises by enzymatic cyclization of precursors having a (5 Z)- or (5′ Z)-configuration.     

Disila‐Galaxolide and Derivatives: Synthesis and Olfactory Characterization of Silicon‐Containing Derivatives of the Musk Odorant Galaxolide

A series of silicon‐containing derivatives of the polycyclic musk odorant galaxolide ( 4 a ) was synthesized, that is, disila‐galaxolide ((4RS,7SR)‐ 4 b /(4RS,7RS)‐ 4 b ), its methylene derivative rac‐ 9 , and its nor analogue rac‐ 10 . The tricyclic title compounds with their 7,8‐dihydro‐6,8‐disila‐6 H‐cyclopenta[g]isochromane skeleton were prepared in multistep syntheses by using a cobalt‐catalyzed [2+2+2] cycloaddition of the mono‐ yne H₂C?CHCH₂OCH₂C?CB(pin) (B(pin)=4,4,5,5‐tetramethyl‐1,3,2‐di‐ oxaborolan‐2‐yl) with the diynes H₂C?C[Si(CH₃)₂C?CH]₂ or H₂C‐ [Si(CH₃)₂C?CH]₂ as the key step. Employing [Cr(CO)₃(MeCN)₃] as an auxiliary, the disila‐galaxolide diastereomers (4RS,7SR)‐ 4 b and (4RS,7RS)‐ 4 b could be chromatographically separated through their tricarbonylchromium(0) complexes, followed by oxidative decomplexation. The identity of the title compounds and their precursors was established by elemental analyses and multinuclear NMR spectroscopic studies and in some cases additionally by crystal structure analyses. Compounds (4RS,7SR)‐ 4 b , (4RS,7RS)‐ 4 b , rac‐ 9 , and rac‐ 10 were characterized for their olfactory properties, including GC‐olfactory studies of the racemic compounds on a chiral stationary phase. As for the parent galaxolide stereoisomers 4 a , only one enantiomer of the silicon compounds (4RS,7SR)‐ 4 b , (4RS,7RS)‐ 4 b , rac‐ 9 , and rac‐ 10 , smelt upon enantioselective GC‐olfactometry, which according to the elution sequence is assumed to be also (4S)‐configured as in the case of the galaxolide stereoisomers. The disila‐analogues (4S,7R)‐ 4 b and (4S,7S)‐ 4 b were, however, about one order of magnitude less intense in terms of their odor threshold than their parent carbon compounds (4S,7R)‐ 4 a and (4S,7S)‐ 4 a . The introduction of a 7‐methylene group in disila‐galaxolide ( 4 b →rac‐ 9 ) improved the odor threshold by a factor of two. With the novel silicon‐containing galaxolide derivatives, the presumed hydrophobic bulk binding pocket of the corresponding musk receptor(s) could be characterized in more detail, which could be useful for the design of novel musk odorants with an improved environmental profile.     

Spirocoleone: Synthese und Charakterisierung von vier diastereomeren Spiro (methylcyclopropan)-Substrukturen; Revision der Konfiguration an C(12) und C(15) von Coleon P und Derivaten sowie von Coleon-Z-Derivaten; Röntgenstrukturanalysen von Lanugon J und weiteren Spirocoleonen

Spirocoleons: Synthesis and Characterization of Four Diastereomeric Spiro (methylcyclopropane) Substructures; Revision of the Configuration at C(12) and C(15) of Coleon P and Derivatives and Coleon-Z Derivatives; X-Ray Analysis of Lanugon J and of Further Spirocoleons X-ray analyses show the correctness of the previously published structure of coleon Q (1) , establish the structure of lanugon J (4a) , and necessitate a revision of the configuration at C(12) and C(15) in coleon P (3a) and its derivatives 3b and 3c , and furthermore of the coleon Z derivatives 11a–11d . Two further diastereomeric spiro (methylcyclopropane) substructures have been generated by photoisomerization of lanugon J (4a) and 12-O-desacetylcoleon N (8) ; they represent the novel cis-type B with (12R, 13R, 15S)- and the novel trans-type D with (12R, 13R, 15R)-configuration (Scheme 1). The structures of the photoproducts 5a ((12R, 13R, 15R)-lanugon J) and 7a ((12R, 13R, 15S)-lanugon J) were established by X-ray analysis. So far, only two of the eight possible diastereomers of the spiro-(methylcyclopropane) substructure I have been detected in nature, i.e. the trans-type A with (12R, 13S, 15S)- and the cis-type C with (12R, 13S, 15R)-configuration. The four diastereomers A-D , all possessing (12R)-configuration, show very similar properties. However, careful comparison of spectral and chiroptical data allow a differentiation, even in the case of functionalization of H₃C(17). The (12S)-counter-parts could not yet be prepared.     

A Reinvestigation of the α-Alkylation of 4-Monosubstituted 2-phenyloxazol-5(4H)-ones (‘azlactones’): A general entry into highly functionalized α,α-disubstituted α-amino acids

Novel, more reliable and general reaction conditions for the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones ( = 4-monosubstituted 2-phenyl-azlactones) rac- 2 to 4,4-disubstituted 2-phenyloxazol-5(4H)-ones rac- 1 were found (Scheme 2). Thus, a whole range of highly functionalized rac- 1 were prepared in medium-to-good overall yields (40-90%, see Table). Azlactones rac- 1 are ideal precursors for the synthesis of optically pure α,α -disubstituted (R)- and (S)-α-amino acids.     

Diastereoselektive Alkylierung von 3-Aminobutansäure in der 2-Stellung

Diastereoselective Alkylation 3-Aminobutanoic Acid in the 2-Position The enantiomerically pure 3-aminobutanoic acids (R)- and (S)- 6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-Methyl 3-(benzoylamino) butanoate ((S)- 3 ) is also available by enzymatic kinetic resolution with pig-liver esterase. The N-benzyl- and N- benzyloxycarbonyl derivatives rac 3 , 8 , and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2). The configuration of three of the products is assigned (Schemes 4–6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3). It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.     

The Chiral Glycine Enolate Derivative from 1-Benzoyl-2-(tert-butyl)-3-methyl-1,3-imidazolidin-4-one is Alkylated in the 5-Position with Relative Topicity lk. Preliminary Communication

An overall enantioselective substitution of the R-group of an α-hydroxy- or α-amino acid 1 [R? CH(XH)COOH] by another R-group is possible through heterocycles 2 obtained from 1 with pivaladehyde ( 1 → 7 ). The rac- and the (S)-(+)-heterocycles 8 (title compounds of type 5 ) are prepared from glycine and O-benzyl-(S)-serine, respectively. Their enolates (cf. 9 , type 6 ) are alkylated with iodomethane, iodobutane, 2-iodopropane, benzyl bromide, and acetone to give the trans-disubstituted imidazolidinones 10 with ≥ 95% diastereoselectivity. The configuration of the products is established by chemical correlation with alanine, phenylalanine, and valine.     

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.     

Multiple Enantioselection by an Enzyme-Catalyzed Transacylation Reaction

Multiply enantioselective enzyme-catalyzed transacylation reactions are described. Two instances of triply enantioselective enzyme-catalyzed transacylations are 1) the reaction of rac-1-indanol with rac-1,1′-bi-2-naphthy]-2,2′-dibutyrate to afford (S)-1-indanoL (R)-1-indanylacetate, (S)-1,1′-bi-2-naphthyl-2,2′-diol, and (R)-1,1′-bi-2-naphthyl-2,2′-dibutyrate and 2) the reaction of rac-1-indanol with rac-2,2′-bis(butyroxymethyl)biphenyl to afford (S)-1-indanol, (R)-1-indanylbutyrate, (S)-2,2′-biphenyldimethanol, and (R)-2,2′-bis(butyroxy-methyl)biphenyl. Doubly enantioselective enzyme-catalyzed transacylations are described according to two instances: 1) the reaction of rac-1-indanol with rac-1,1′-bi-2-naphthyl-2-ol-2′-butyrate afforded (S)-1-indanol, (R)-1-indanylacetate, (S)-1,1′-bi-2-naphthyl-2,2′-diol, and (R)-1,1′-bi-2-naphthyl-2-ol-2′-butyrate, and 2) the reaction of rac-1-indanol with 1,3,5-O-methylidne-2,4,6-tri-O-butyrate-myo-inositol to afford (S)-1 -indanol, (R)-l-indanylbutyrate, and 1,3,5-O-methylidne-2,6-di-O-butyrate-myo-inositol. Multiply enantioselective enzyme-catalyzed reactions have a merit of the enhancement of enantiomeric excess over singly enantioselective ones.     

Über die Stereoselektivität der α-Alkylierung von (1R, 2S) (+)-cis-2-hydroxy-cyclohexancarbonsäureäthylester

The Stereoselectivity of the α-Alkylation of (+)-(1R, 2S)-cis-Ethyl-2-hydroxy-cyclohexanecarboxylate In continuation of our work on the stereoselectivity of the α-alkylation of β-hydroxyesters [1] [2], we studied this reaction with the title compound (+)- 2 . The latter was prepared through reduction of 1 with baker's yeast. Alkylation of the dianion of (+)- 2 furnished (?)- 4 in 72% chemical yield (Scheme 1) and with a stereoselectivity of 95%. Analogously, (?)- 7 was prepared with similar yields. Oxidation of (?)- 4 and (?)- 7 respectively furnished the ketones (?)- 6 (Scheme 3) and (?)- 8 (Scheme 4) respectively, each with about 76% enantiomeric excess (NMR.). It is noteworthy that yeast reduction of rac- 6 (Scheme 3) is completely enantioselective with respect to substrate and product and gives optically pure (?)- 4 in 10% yield, which was converted into optically pure (?)- 6 (Scheme 3). The alkylation of the dianionic intermediate shows a higher stereoselectivity (95%) from the pseudoequatorial side than that of 1-acetyl- or 1-cyano-4-t-butyl-cyclohexane (71% and 85%) [9] or that of ethyl 2-methyl-cyclohexanecarboxylate (82%). The stereochemical outcome of the above alkylation is comparable with that found in open chain examples [1] [2]. Finally (+)-(1R, 2S)- 2 was also alkylated with Wichterle's reagent to give (?)-(1S, 2S)- 9 in 64% yield. The latter was transformed into (?)-(S)- 10 and further into (?)-(S)- 11 (Scheme 5). (?)-(S)- 10 and (?)-(S)- 11 showed an e.e. of 76–78% (see also [11]). Comparison of these results with those in [11] confirmed our former stereochemical assignment concerning the alkylation step.     

Syntheses,spectroscopy, and catalysis of (η 4-cod)Rh(I)-complexes with (R or S)-2-(salicylaldimine)-2-phenylethanol or (rac)-2-(salicylaldimine)-1-phenylethanol

Condensation of salicyldehyde with (R or S)-2-amino-2-phenylethanol or rac-2-amino-1-phenylethanol gives enantiopure (R or S)-2-(salicylaldimine)-2-phenylethanol (R- or S-H₂L1) or (rac)-2-(salicylaldimine)-1-phenylethanol (rac-H₂L2). The Schiff bases coordinate to [Rh(η ⁴-cod)(μ-O₂CCH₃)]₂ to afford mononuclear [Rh(η ⁴-cod){(R or S)-2-(salicylaldiminato)-2-phenylethanol-κ ² N,O}], [Rh(η ⁴-cod)(R- or S-HL1)] (1 or 2), or [Rh(η ⁴-cod){(rac)-2-(salicylaldiminato)-1-phenylethanol-κ ² N,O}], [Rh(η ⁴-cod)(rac-HL2)] (3). The Schiff base and complexes are characterized by IR-, UV/Vis-, ¹H/¹³C-NMR-, mass-spectroscopy, circular dichroism (CD), and polarimetry. The synthetic and spectroscopic results suggest that deprotonated Schiff base coordinates to [Rh(η ⁴-cod)] as a six-membered N,O-chelate with distorted square planar geometry at rhodium. CD and polarimetry measurements show the enantiopurity of the Schiff bases as well as the complexes in solution. The in situ system composed of [Rh(η ⁴-cod)Cl]₂ and S-H₂L1 has been used as a catalyst for the reduction of acetophenone into rac-1-phenylethanol with 85% conversion in diphenylsilane at 0–5°C.     

Asymmetric Total Synthesis of (11R, 12S, 13S, 9Z, 15Z)-9, 12, 13-Trihydroxyoctadeca-9, 15-dienoic Acid,a self-defensive agent against rice-blast disease

The Diels-Alder adduct of furan and 1-cyanovinyl (1′R)-camphanate was converted into methyl [(tert-butyl)-dimethylsilyl 5-deoxy-2, 3-O-isopropylidene-β-L -ribo-hexofuranosid] uronate ((+)- 4 ). Reduction with diisobutyl-aluminium hydride gave the corresponding aldehyde which was condensed with the ylide derived from triphenyl-(propyl)phosphonium bromide to give (1R, 2S, 3S, 4S)-1-[(tert-butyl)dimethylsilyloxy]tetrahedro-2, 3-(isopropyl-idenedioxy)-4-[(Z)-pent-2′ -enyl]furan ((+)- 7 ). Removal of the silyl protective group gave a mixture of the corresponding furanose that underwent Wittig reaction with the ylide derived from [8-(methoxycarbonyl)-octyl]triphenylphosphonium bromide to yield methyl (11R, 12S, 13S, 9Z, 15Z)-13-hydroxy-11, 12-(isopropylidene-dioxy)octadeca-9, 15-dienoate ((?)- 9 ). Acidic hydrolysis, then saponification afforded (11R, 12S, 13S, 9Z, 15Z)-11, 12, 13-trihydroxyoctadeca-9, 15-dienoic acid ( 1 ).     

Synthese von N-Methyl- und N,N-Dimethylmerucathin sowie von N-Methyl- und N,N-Dimethylpseudomerucathin aus L-Alanin

Synthesis of N-Methyl- and N,N-Dimethylmerucathine and of N-Methyl- and N,N--Dimethylpseudomerucathine Starting from L -Alanine Starting form L -alanine, N-methylmerucathine (= (3R,4S)-4-(methylamino)1-phenyl-1-penten-3-ol; (3R,4S,)- 6 ), N,N-dimethylmerucathine (= (3R,4S)-4-(dimethylamino)-1-phenyl-1-penten-3-ol; (3R,4S)- 9 ), N-methylpseudomerucathine (= (3S,4S)-4-(methylamino)-1-phenyl-1-penten-3-01; (3S,4S)-6), and N,N-dimethylpseudomerucathine (= (3S,4S)-4-(dimethylamino)-1-phenyl-1-penten-3-ol; (3S,4S)- 9 ) were synthesized. The four compounds were analyzed by HPLC and compared with a natural khat extract.     

Konkurrenz von Endoperoxid- und Hydroperoxid-Bildung bei der Umsetzung von Singulett-Sauerstoff mit cyclischen,konjugierten Dienen. Teil I

Competition of Endoperoxide and Hydroperoxide Formation in the Reaction of Singlet Oxygen with Cyclic, Conjugated Dienes Rose-bengal-sensitized photooxygenation of (?)-(R)-α-phellandrene ( 1 ) in MeOH at room temperature yielded a complex mixture of products, contrary to previous reports describing cis-(3S, 6R)-epidioxy-p-menthene ( 2 ) and trans-(3R, 6S)-epidioxy-p-menthene ( 3 ) as the only products. The mixture was separated by prep. HPLC (silica gel, pentane/Et₂O 9:1). Besides the known endoperoxides 2 (yield 39%) and 3 (26%), all those hydroper-oxides, which can be deduced from an ene reaction of ¹O₂ with 1 , were isolated, i.e. 4β-p-mentha-2,5-dien-1β-yl hydroperoxide ( 4 ) (14%), 4β-p-mentha-2,5-dien-1α-yl hydroperoxide ( 5 ) (9%), (2R, 4R)-p-mentha-1(7), 5-dien-2-yl hydroperoxide ( 6 ) (2,1%), (2S, 4R)-p-mentha-1(7),5-dien-2-yl hydroperoxide ( 7 ) (1,5%) and (1R)-p-mentha-3,6-dien-yl hydroperoxide ( 8 ; 1,5%; Scheme 1). Furthermore, the constant cis/trans ratio for all diastereoisomeric pairs ( 2 / 2 , 4 / 2 , 6 / 2 ) was striking. With the help of the two possible conformers 1a and 1b of the starting material a model of a common first step for endoperoxide as well as for hydroperoxide formation is developed. A photooxygenation at ?50° supports this model. The absolute value of the cis/trans ratio changes in the same way for the endoperoxides and the hydroperoxides.     

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.     

Synthese von enantiomerenreinen Violaxanthinen und verwandten Verbindungen

Syntheses of Enantiomerically Pure Violaxanthins and Related Compounds The epoxides 16 and ent- 16 , prepared by Sharpless-Katsuki oxidation of 15 in excellent yield and very high enantiomeric purity, were used as synthons for the preparation of (+)-(S)-didehydrovomifoliol (45) , (+)-(6S, 7E, 9E)-abscisic ester 46 , (+)-(6S, 7E, 9Z)-abscsic ester 47 , (?)-(3S, 7E, 9E)-xanthoxin (49) , (?)-(3R, 7E, 9E)-xanthoxin (50) , (3S, 5R, 6S, 3′S,5′R, 6′S, all-E)-violaxanthin (1) (3R, 5R,6S,3′R,5′R,6′S, all-E)-violaxanthin (55) and their (9Z) (see 53 , 57 ), (13Z) (see 54 , 58 ), and (15Z) (see 60 ) isomers. The novel violadione ( 61 ) was prepared from 1 by oxidation with DMSO/Ac₂O. By base treatment, 61 was converted into violadienedione (62) , a potential precursor of carotenoids with phenolic end groups.     

Partialsynthesen und Reaktionen von Abietanderivaten (Lanugonen) aus Plectranthus lanuginosus und verwandten Verbindungen

Partial Syntheses and Reactions of Abietanoid Derivatives (Lanugones) from Plectranthus lanuginosus and of Related Compounds Interconversions by partial syntheses of several lanugones establish their absolute configuration at C(15). Unexpected reactions exemplify the unique reactivity of these abietanoic diterpenes, - Lanugone O ( 4 ) was prepared in several steps from (15S)-coleon C ( 8a ; Scheme 2) thus establishing its (15S)-configuration. One of the intermediates, the 12-O-acetyl-6-oxoroyleanone 12 , through acetyl-migration sets up an equilibrium with the vinylogous quinone 13 (Scheme 3). - The chirality at C(15) in the dihydrofuran moiety of lanugone Q ( 16 ) was proven by acid-catalyzed conversion of lanugone O ( 4 ) to 16 . - Instead of the usual nucleophilic attack shown by quinomethanes, lanugone L (1 ) is electrophilically substituted at C(7) by acetic anhydride/pyridine (Scheme 1). - In a homosigmatropic [1,5]-H-shift, lanugone G ( 17 ) in solution is converted to the corresponding allyl substituted royleanone 18 (Scheme 4). - Methanolysis of lanugone J ( 19 ) leads to the expected royleanone 20 having the 2-methoxypropyl side chain ( Scheme 5 ). Similar reactions were found in acetolytic reactions. However, treatment-of spirocoleons with SOCl₂/DMF produces mainly 12-deoxyroyleanones with allyl- and 2-chloropropyl groups, i. e. 19 → 26 and 27 ; 28 → 29 . The possible natural occurrence of these compounds is emphasized.     

Synthese von Trifluoromethyl-substituierten Schwefel-Heterocyclen unter Verwendung von 3,3,3-Trifluorobrenztraubensäure-Derivaten

Synthesis of Trifluoromethyl-Substituted Sulfur Heterocycles Using 3,3,3-Trifluoropyruvic-Acid Derivatives The reaction of methyl 3,3,3-trifluoropyruvate ( 1 ) with 2,5-dihydro-1,3,4-thiadiazoles 4a, b in benzene at 45° yielded the corresponding methyl 5-(trifluoromethyl)-1,3-oxathiolane-5-carboxylates 5a, b (Scheme 1) via a regioselective 1,3-dipolar cycloaddition of an intermediate ‘thiocarbonyl ylide’ of type 3 . With methyl pyruvate, 4a reacted similarly to give 6 in good yield. Methyl 2-diazo-3,3,3-trifluoropropanoate ( 2 ) and thiobenzophenone ( 7a ) in toluene underwent a reaction at 50°; the only product detected in the reaction mixture was thiirane 8a (Scheme 2). With the less reactive thiocarbonyl compounds 9H-xanthene-9-thione ( 7b ) and 9H-thioxanthene-9-thione ( 7c ) as well as with 1,3-thiazole-5(4H)-thione 12 , diazo compound 2 reacted only in the presence of catalytic amounts of Rh₂(OAc)₄. In the cases of 7a and 7b , thiiranes 8b and 8c , respectively, were the sole products (Scheme 3). The crystal struture of 8c has been established by X-ray crystallography (Fig.). In the reaction with 12 , desulfurization of the primarily formed thiirane 14 gave the methyl 3,3,3-trifluoro-2-(4,5-dihydro-1,3-thiazol-5-ylidene)propanoates (E)-and (Z)- 15 (Scheme 4). A mechanism of the Rh-catalyzed reaction via a carbene addition to the thiocarbonyl S-atom is proposed in Scheme 5.     

Über die Totalsynthese vo Betalainen

On the Total Synthesis of Betalains Improved total syntheses of the red-violet aglucone of the beet coloring matter and of the yellow cactus coloring matter indicaxanthine are presented. Formyl-olefination of the piperidone-diester 6 with the acetaldehyde synthon 5 led to the piperidylidene-acetaldehyde derivative 8 , which was converted into the 2,4,4-trimethylsemicarbazone of rac-betalamic acid dimethyl ester (10) by treatment with t-BuOCl and then Et₃N. Exchanging the semicarbazone moiety with the (S)-cyclodopa derivative 18 , with (S)-proline (19) and with indoline (20) transformed 10 to betanidin (21/22) , to indicaxantihin (23/24) and to rac-indo-betalaine (25) , respectively. The latter, a new, relatively stable betalaine, was hydrolyzed and esterified to rac-betalamic acid dimethyl ester (29) . Under the influence of NH₃/MeOH, 26 (the dimethyl ester of 25 ) was dehydrogenated spontaneously to indo-neobetalaine dimethyl ester (27) . Synthetic betanidin consisted of a 4:6 mixture of the (natural) (2S, 15S)- (21) and the (2S, 15R)-isomer (22) and both of a 75:25 mixture of the (E)- and the (Z)-isomer. Synthetic indicaxanthin (23/24) and the indo-betalaine (25) represented a 65:35 and a 70:30 mixture, respectively, of (E)- and the (Z)-isomers. All (E)- and (Z)-isomers are rapidly interconvertible. Temperature-dependent ¹ H-NMR -measurements of 25 established ΔG≠ = 84.7 kJ/mole for the (E)-to-(Z)-conversion. The t-BuOCl/NEt₃ method for the introduction of an enaminic double bond was applied to the model transformations of the amines 6, 12 and 15 to the conjugated enamiens 11, 13 and 17 , respectively.     

Synthesis of New Chiral Bidentate (Phosphinophenyl)benzoxazine P,N-Ligands

Two new chiral bidentate (phosphinophenyl)benzoxazine P,N-ligands 2a and 2b were synthesized from highly enantiomer-enriched 2-(1-aminoalkyl)phenols 4 . Ligand rac- 2a was obtained on refluxing the t-Bu-substituted (aminomethyl)phenol 4a with 2-(diphenylphosphino)benzonitrile in chlorobenzene in the presence of anhydrous ZnCl₂ followed by decomplexation (Scheme 2). This reaction, when carried out with (+)-(S)- 4a , was accompanied by racemization at the stereogenic center of the alkyl side chain. The enantiomerically pure ligands (+)-(R)- 2a and (−)-(S)- 2a were obtained using a stepwise procedure via the amides (−)-(R)- and (+)-(S)- 5b , respectively, followed by cyclization to benzoxazines (+)-(R)- and (−)-(S)- 7b , respectively, with triflic anhydride and by F-atom substitution by diphenylphosphide (Schemes 3 and 5). In the case of the i-Pr analogue 2b , this last step resulted in racemization (Scheme 6). This was overcome by preparing the bromo derivative and introducing the diphenylphosphine group via Br/Li exchange and reaction with chlorodiphenylphosphine (Scheme 7). The first application of (+)-(R)- 2a in an asymmetric Heck reaction showed high enantioselectivity (91%) (Scheme 8).     

Reduktive Co-Alkylierung von Heptamethyl-cobyrinat mit dem Methylthiomalonat (S)-Methyl-3-bromo-2-[(ethylthio) carbonyl]-2-methylpropanoat

Reductive Co Alkylation of Heptamethyl Cobyrinate with the Methylthiomalonate (S)-Methyl 3-Bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate The methylthiomalonate(?)-(S)-Methyl 3-bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate( 5a )was prepared from dimethyl methylmalonate in five steps via the stereospecific cleavage of the (pro-S)-ester group of 1 with pig-liver esterase in an overall yield of 26.5% (Scheme 4a). Reductive Co alkylation of heptamethyl Coβ-perchlorato cob (II)yrinate ( 8 ) with 5a by electrosynthesis lead to the alkylcobalt complex 9a in 40% yield (Scheme 4b). The O2-dependent reactions of the methyhnalonyl fragment produced by photolysis of 9a and its deuterated derivative 9c are reported (Scheme 5).