Experiments on a simulation of the photochemical A/D-secocorrin leads to corrin cyclo-isomerization by redox processes. Electrochemical oxidation of nickel(II)-1-methylidene-2,2,7,7,12,12-hexamethyl-15-cyano-1,19-secocorrinate perchlorate (author's transl)]

Experiments on a simulation of the photochemical A/D-secocorrin → corrin cycloisomerization by redox processes. Electrochemical oxidation of nickel(II)-1-methylidene-2,2,7,7,12,12-hexamethyl-15-cyano-1,19-secocorrinate perchlorate Can the act of light excitation in the photochemical A/D-secocorrin → corrin cycloisomerization be replaced by redox reactions in the dark? Electrochemical oxidation of nickel(II)-A/D-secocorrinate 4 in acetonitrile containing a trace of water produces the secocorrinoxide–nickel-complex 5 (structure determined by X-ray analysis) in almost quantitative yield. This two-electron oxidation involves a hydrogen shift from the methylene group C(19) in ring D to the methylidene carbon atom at ring A in the radical cation intermediate. Since the same type of hydrogen shift occurs in the photochemical A/D-secocorrin → corrin cycloisomerization, a close parallelism in their chemical reactivity seems to exist between electronically excited A/D-secocorrins and corresponding radical cations. Formation of the corrin complex 2 (M = Ni⁺) could be achieved (so far only in modest yields) by electrochemical one-electron oxidation of 4 in acetonitrile/acetanhydride/acetic acid 8:1:1 followed by one-electron reduction. – The transformation of the oxide nickel complex 5 to the corrinoid complex 10 – a new member in the family of dehydrocorrins – is also recorded.     

Synthetische Verwendung von Epoxynitronen. II. Synthese von Steroid-α-methyliden-γ-lactonen

Synthetic application of epoxynitrones. II. Syntheses of steroidal α-methylidene-γ-lactones This communication describes the application of the epoxynitrone/CF₃SO₃SiR₃ → 1,2-oxazine annelation-reaction [1] to the syntheses of steroidal α-methylidene-γ-lactones from olefines, e.g. 12 → 14a/b → 16a/b → 18a/b → 20 → 22 (Scheme 2).     

Aufbau der Ligandsysteme des C,D-Tetradehydrocorrins und Isobakteriochlorins durch Sulfidkontraktion. Kurzmitteilung

Synthesis of C, D-Tetradehydrocorrins and Isobacteriochlorins via Sulfide Contraction The reaction sequences shown in Schemes 4 and 5 illustrate the use of the sulfide contraction method for the synthesis of isobacteriochlorins and (metal free) C, D-tetradehydrocorrins. The tetradehydrocorrin synthesis fills a gap in a spectrum of corrinoid (A → D) ring closures that ranges from A.W. Johnson's oxidative (A → D)-cyclizations to octadehydrocorrinoids on the one side to the photochemical 1, 19-secocorrin → corrincycloisomerization on the other (Scheme 7). Such a multiplicity of reaction paths towards corrinoids is of interest in connection with the problem of the origin of the corrin structure.     

Desoxy-nitrozucker. 13. Mitteilung. Herstellung ungeschützter und partiell geschützter 1-Desoxy-1-nitro-D-aldosen sowie Röntgenstrukturanalysen einiger ihrer Vertreter

Preparation of Unprotected and Partially Protected 1-Deoxy-1-nitro-D -aldoses and Some Representative X-Ray Structure Analyses The unprotected and partially protected 1-deoxy-1-nitro derivatives of α-and β-D -glucopyranose (see 15 and 14 ), β-D -mannopyranose (see 16 ), N-acetyl-β-D -glucosamine (see 17 ), β-D -galactofuranose (see 19 ), β-D -ribofuranose (see 20 ), α-D -arabinofuranose (see 21 ), 4,6-O-benzylidene-β-D -glucose (see 40 ), N-acetyl-4,6-O-benzylidene-β-D -glucosamine (see 41 ), and 4,6-O-benzylidene-β-D -galactose (see 42 ) were prepared by ozonolysis of the corresponding nitrones which were obtained from the acid-catalyzed reaction of p-nitrobenzaldehyde with the hydroxylamine 4 , the unprotected oximes 3 and 5–9 and the 4,6-O-benzylidene oximes 35–37 , respectively (Schemes 1–3). The gluco- and manno-nitrones 10 and 12 were isolated, and their ring size and their anomeric and (E/Z) configurations were determined by NMR spectroscopy and by their transformation into their corresponding nitro derivatives. The structure of the deoxynitroaldoses were determined by NMR spectroscopy, polarimetry, and, in the case of 14 , 16 , and 17 , by formation of the 4,6-O-benzylidene ( 14 → 40 ) or 4,6-O-isopropylidene ( 16 → 43 , 17 → 23 ) derivatives (Scheme 3). Acetylation of the nitroglucopyranose 14 , the 2-acetamido-nitroglucopyranose 17 , and the nitrogalactofuranose 19 gave the crystalline peracetylated nitroaldoses 22 , 24 , and 45 , respectively (Scheme 4, Figs. 1 and 3); acetylation of the nitromannopyranose 16 gave the nitro-arabino-glycal 44 (Scheme 4). The structure of the peracetylated nitroglucopyranose 22 , the nitroglucosamine 25 , the nitrogalactofuranose 45 , and the nitroribofuranose 20 were confirmed by X-ray analysis (Figs. 1 4). In all cases, including the β-D -glucopyranose derivative 22 , considerably shortening of the (endocyclic) C(1)-O bond was observed. Base-catalyzed anomerization of the β-D -configurated nitroglucopyranose 14 , the nitromannopyranose 16 , the benzylidene acetal 40 of nitroglucose, and the 2,3,4,6-tetraacetylated glucosamine derivative 24 gave the corresponding nitro-α-D -aldoses 15 , 26 , 47 , and 25 , respectively (Scheme 4).     

Synthese und reduktive Cyclisierung eines Δ18-Dehydro-A/D-secocorrinkomplexes

A Δ¹⁸-dehydro-A/D-secocorrin complex has been synthesized and shown to cyclize smoothly to the corresponding corrin complex by electrochemical reduction in a protonating medium. The crucial step of the construction of the secocorrinoid substrate illustrates a novel variant of the Bamford-Stevens reaction.     

Synthetische Verwendung von Epoxynitronen. I. N-(2,3-Epoxypropyliden)-cyclohexylamin-oxid,ein neues Reagens zur Synthese von α-Methyliden-γ-lactonen aus Olefinen

Synthetic Application of Epoxynitrones I. Nitrone, a New α-Methylidene-γ-lactone Annelating Reagent The N-(2, 3-epoxypropyliden)-cyclohexylamine-N-oxide/CF₃SO₃SiR₃ reagent descried in this communication opens a new and interesting entry to the versatile N-substituted N-propenylnitrosonium ions of type b (Scheme 6). One of the uses of this reagent is shown to be the synthesis of α-methylidene-γ-lactones from olefins. This new method shows similar features as the method based on 2, 3-dichloropropylidenamine-oxide/AgBF₄ originally developed for the same purpose by Petrzilka, Felix and Eschenmoser. Epoxynitrone 18 can be transformed to the positively charged heterodiene of type b (Scheme 5) using the highly electrophilic reagents CF₃SO₃SiMe₃ ( 23 ) and CF₃SO₃Si (t-Bu)Me₂ ( 24 ), respectively. Low temperature ¹H- and ¹³C-NMR. spectroscopy at ?78° showed the sole formation of the nitrone-O-silyl-ethers a (Scheme 5). Epoxid opening leading to the diene b and subsequent reactions are observed only at about ?30°. The diene b prepared in situ, adds to isolated double bonds by way of an inverse Diels-Alder reaction to afford cycloadducts of type 27 (Scheme 7). Their stable cyanoderivatives, e.g. 28 (Scheme 7), can be isolated and transformed via 31 , 44 and 54 into cis annelated α-methylidene-γ-lactones of type 55 (Scheme 11). Using trisubstituted olefins, substitution at the lower substituted olefinic C-atom competes efficiently with the cycloaddition (e.g. 34 , Scheme 8).     

Synthesen des Analgetikums 2-[1-(m-Methoxyphenyl)-2-cyclohexen-1-yl]-N,N -dimethyl-äthylamin

Syntheses of the Analgesic 2-[1-(m-Methoxyphenyl)-2-cyclohexen-1-yl] -N,N-dimethyl-ethylamine Three principal routes to 2-[1-(m-methoxyphenyl)-2-cyclohexen-1-yl]- N,N-dimethyl-ethylamine (13) , a compound with interesting analgesic properties, are described. In the first, derivatives of [1-(m-methoxyphenyl)-2-cyclohexen-1-yl]acetic acid (10) (alternatively the ethyl ester 29 , the dimethylamide 32 or the nitrile 34 ) serve as crucial intermediates. All three can be synthesized from 2-(m-methoxyphenyl)cyclohexanone (1) by sequences comprising successively C-alkylation ( 1→2,4,5; Scheme 1), reduction of the ketone carbonyl group ( 2→6;4→18;5→19; Scheme 1 and 2) and elimination ( 16→29; 18→32; 19→34; Scheme 2). The relative configuration of the cyclohexanols 16, 18, 19 and of a series of related compounds is established by chemical correlation with the lactone 30 the structure of which follows from ¹H-NMR. data (Scheme 2). The second route creates the intermediates 29 and 32 by ester- or amide-enolate-Claisen-type-rearrangement reactions starting from 3-(m-methoxyphenyl)-2-cyclohexen-1-ol ( 39; Scheme 3). Compounds 29, 32 and 34 are transformed into the target molecule 13 by standard reactions. A Hofmann elimination of the quaternary ammonium fluoride 50 (X=F), derived from the known cis-perhydroindoline 48 , is the essential step in the third approach to 13 (Scheme 4).     

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.     

Generation and Trapping of Triafulvene

Substituted methylidenecyclopropanes 12a – d , being easily available from 1,1-dibromo-2-(phenylthio)-cyclopropane ( 9a ), are attractive precursors of triafulvene (2-methylidene-1-cyclopropene; 1 ). Both the sulfoxide 12b and the sulfone 12c react with an excess of alkoxides (t-BuOK and NaOMe) to give 12e and 12f , respectively, while the sulfinyl group of 12b may be replaced by the PhCH₂S substituent in the presence of PhCH₂SH/t-BuOK. These reactions (Scheme 4) may be explained by assuming 1 as a reactive intermediate, although an alternative sequence including carbene 20 (Scheme 6) is not completely ruled out. D -labelling experiments (Scheme 5) do not give conclusive evidence due to D scrambling, but deprotonation/methylation sequences show that H? C(2) of 12a – c is the most acidic proton. Final evidence for 1 results from the reaction of 12d with cyclopentadienide (Scheme 7): the reaction of 1 with cyclopentadiene produces the expected [4 + 2]-cycloaddition product 23 , while some mechanistic insight results from the sequence 12d → 24 → 25 .     

Über 3,3,6,9,9-Pentamethyl-2,10-diaza-bicyclo-[4.4.0]-1-decen und einige seiner Derivate. Über synthetische Methoden. 13. Mitteilung

3,3,6,9,9-Pentamethyl-2,10-diaza-bicyclo[4.4.0]-1-decen and some of its derivatives A simple synthesis for the bicyclic amidine 1 (Scheme 3) is described. This base and the salts which were prepared from it show solubility characteristics which make the amidine a potentially useful reagent for salt formation of carboxylic acids and related proton complexes of bidentate ligands. Among the derivatives made from 1 are the sterically strongly hindered N-alkylated amidines 11 , 12 and 14 (Scheme 5), as well as the stable crystalline N¹-oxidoamidine-N²-oxyl radical 2 (Scheme 6). The ability of the latter to serve as a paramagnetic chelating ligand for metal ions is illustrated by the preparation of a corresponding nickel(II) complex. The radical is also a source for the α-nitronyl-nitrosonium cation 4 which shows in its reactivity towards conjugated dienes and olefines some of the expected resemblance to singlet oxygen.     

3-Triethylsilyloxypentadienyllithium,a Versatile 1,3-Diene- or Vinyl Ketone-Building Block

Deprotonation of the 3-trialkylsilyloxy-1,4-diene 3a and subsequent electrophilic substitution of the non-isolated 3-trialkylsilyoxypentadienyllithium 4 gives the α- and γ-products 8 and/or 6 in good yields. Whereas alkylation of 4 proceeds with variable regioselectivity (Table 1) aldehydes and ketones attack preferentially the γ-position of 4 (Table 2). The desired γ-products 6 may be directly subjected to inter- and intramolecular [4 + 2]-additions as demonstrated by the reactions 5a (? 6d ) → 7 and 6h → 19 (Schemes 4 and 12). Alternatively, smooth fluoride-promoted silylether-cleavage 6 → 11 (Scheme 8) provides a convenient approach to substituted vinyl ketones such as to the natural products 11f (Table 3). The stereoselective conversion 6k → 23 (Scheme 13) implies an endo-selective intramolecular Diels-Alder addition ( 26 → 23 ) and exemplifies the use of 4 as an equivalent of the hypothetical anion IV . Furthermore, some electrophilic substitutions of the hexadienyllithium 15 have been studied (Scheme 10).     

Synthese von Triafulven-Vorstufen für Retro-Diels-Alder-Reaktionen

Synthesis of Triafulvene Precursors for Retro-Diels-Alder Reactions Triafulvene precursors exo? 15 and endo? 15 have been prepared by addition of dibromocarbene to benzobarrelene 12 followed by a lithium-halogen exchange, methylation, and elimination of HBr ( 12→13→14→15 ), (Scheme 2). Gas-phase pyrolysis of exo/endo-mixtures of 15 above 400° gave minor amounts of naphthalene ( 16 ), traces of a hydrocarbon C₄H₄ identified by MS (presumably triafulvene 1 ) and predominantly (36%) the isomerization product 17 (Scheme 3). In a second synthetic approach the well-known cycloheptatriene-norcaradiene equilibrium of type 26?27 has been utilised to prepare various endo-trans-3-(X-methyl) tricyclo[3.2.2.0^2,4]nona-6,8-dienes 31 (Scheme 5). However, numerous elimination experiments 31→9 failed so far. The structure of two rearrangement products 33 and 34 (Scheme 6) has been elucidated.     

Heterodiamantane und strukturell verwandte Verbindungen. III.. Pentacyclische diäther der C11-reihe. 5, 13-Dioxapentacyclo-[6.5.0.02,6.03,12.04,9]tridecan, 4, 13-dioxapentacyclo [6.4.1.02,7.03,10.05,9]tridecan und 3, 10-dioxapentacyclo [7.3.1.02,7.04,12.06,11]tridecan

Heterodiamantanes and Structurally Related Compounds. Part III. The Pentacyclic C₁₁-Diethers 5, 13-Dioxapentacyclo [6.5.0.0^2,6.0^3,12.0^4,9]tridecane, 4, 13-Dioxapentacyclo [6.4.1.0^2,7.0^3,10.0^5,9]tridecane, and 3, 10-Dioxapentacyclo [7.3.1.0^2,7.0^4,12.0^6,11]tridecane In connection with the studies on heterodiamantanes and structurally related compounds the three novel pentacyclic diethers 3 – 5 were prepared starting from the cyclopentadienone dimer 6 . All four compounds have as common features a central carbocyclic 6-membered ring with four axial alkyl substituents and two oxygen functions in 1, 4 position. The required eleventh C-atom was introduced by dichlorocarbene addition either to 6 ( → 7 ) (Scheme 2) or to 29 ( → 28 ) (Scheme 4). Diether 3 was obtained by reduction of 26 (Scheme 2), a suitable precursor prepared either by intramolecular addition ( 24 → 26 ; Scheme 2) or substitution ( 30 → 26 , 31 → 26 ; Scheme 4), as well as by direct substitution ( 44 → 3 , 42 → 3 ; Scheme 5). Diether 4 was the product of a direct substitution ( 39 → 4 , 36 → 4 ; Scheme 5). The synthesis of diether 5 was achieved from the addition product 51 (resulting from the alcohols 47 and 48 ; Scheme 6). Diether 4 is the thermodynamically least stable of the three diethers 3 – 5 . It was easily isomerized to 5 on treatment with concentrated sulfuric acid in benzene whereas 3 and 5 remained unchanged under these conditions.     

Spezifisch π→π*-induzierte Reaktionen von γ-Dimethoxymethylcyclohexen-2-onen: 1,3-Umlagerung und Wasserstoffabstraktion durch das α-Kohlenstoffatom

When α,β-unsaturated γ-dimethoxymethyl cyclohexenones are excited to the S₂(π,π*) state, certain unimolecular reactions can be observed to compete with S₂ → S₁ internal conversion. These reactions do not occur from the S₁(n,π*) or the lowest T(π,π* and n,π*) states. They comprise the radical elimination of the formylacetal substituent (cf. 8 , 9 → 32 + 33 ), γ → α formylacetal migration (cf. 6 → 27 , 8 → 30 , 9 → 34 , 12 → 37 ), and a cyclization process involving the transfer of a methoxyl hydrogen to the α carbon and ring closure at the β position (cf. 6 → 28 , 8 → 31 , 12 → 38 , 20 → 40 + 41 ). The quantum yield of the ring closure 20a → 40a + 41a is 0.016 at ≤ 0.05M concentration. It is independent of the excitation wavelength within the π→π* absorption band (238–254 nm), but Φ ( 40a + 41a ) decreases at higher concentrations. According to the experimental data the reactive species of these specifically π→π*-induced transformations is placed energetically higher than the S₁(n,π*) state, and it is either identical with the thermally equilibrated S₂(n,π*) state, or reached via this latter state. The linear dienone 14 undergoes a similar π→π*-induced cyclization (→ 42 ) whereas the benzohomologue 26 proved unreactive, and the dienone 22 at both n → π and π→π* excitation only gives rise to rearrangements generally characteristic of cross-conjugated cyclohexadienones.     

Von der basenkatalysierten Ringöffnung von 2H-Azirinen zu einer α-Alkylierungsmethode von primären Aminen

From a Base Catalyzed Ring Opening of 2H-Azirines to an α-Alkylation Method of Primary Amines It is shown that fluorene-9′-spiro-2-(3-phenyl-2H-azirine) ( 1 ) on treatment with various alcohols in the presence of the corresponding alkoxide ions yields N-(9′-fluorenyl)benzimidates 2a-d (Scheme 1). 2,2,3-Triphenyl-2H-azirine ( 3 ) reacts with methanol in a similar manner (Scheme 2). Benzimidates 2a (Scheme 3), 8 (Scheme 4) and and 10 (Scheme 5) can easily be deprotonated by butyllithium (BuLi) or lithium diisopropylamide (LDA) in tetrahydrofuran (THF) to 1-methoxy-2-aza-allylanions, that can be alkylated, at C(3), exclusively, by various electrophiles (e.g. R-X(X = I, Br), RCHO or methyl acrylate (see also Scheme 6)). As the acidic hydrolyses (1N HCl) of benzimidates 9 and 11 leads to the corresponding α-alkylated free amines 15 and 18 (Scheme 7 and 8), benzoyl derivatives 16 and 19 are obtained from the hydrolysis under basic conditions. On the other hand, it is observed that a catalyzed Chapman rearrangement of 9 and 11 results in the formation of N-benzoyl-N-methyl derivatives 17 and 20 (Scheme 7 and 8). The described reactions offer a simple method for the α-alkylation of activated primary amines.     

Steroide und Sexualhormone. 261. Mitteilung. Quassinoide Bitterstoffe II. Partialsynthetischer Zugang zu Quassin: Überführung von Testosteron in eine Schlüsselverbindung mit angulärer 8β-Methylgruppe

Partial Synthesis of Quassin: Synthesis of a Key Intermediate with an Angular 8β-Methyl Group from Testosterone A key intermediate in the partial synthesis of quassin ( 1 ) was synthesized in 28 steps starting from testosterone ( 9 ) (Scheme 3). The key features are: (i) The conversion of testosterone ( 9 ) into the 1α, 2β, 3β-O-substituted 4α-methylandrostane 19 (Scheme 3) and its transformation into an intermediate 26 with the ring A partial structure of quassin (Scheme 4). (ii) The conversion of 19 to the vinylogous α-hydroxyketone 5 (Scheme 6 and 7). (iii) The photochemically induced [2+2]-cycloaddition of allene to hydroxyenone 5 , affording the 8β, 14β-cyclobutano-derivative 6 (Scheme 2 and 8). (iv) The conversion of 6 into the key compound 7 . In connection with this last transformation a new method for the degradation of phenylselenoesters of carboxylic acids to the corresponding nor-alkanes was developed (see Scheme 8). Details of this reaction will be published elsewhere [18].     

Anwendung der α-Alkinon-Cyclisierung: Synthese von rac-Modhephen

Application of the α-Alkynone Cyclization: Synthesis of rac-Modhephene rac-Modhephene 1 , the first sesquiterpene with a propellane C-skeleton and its epimer rac-epi-modhephene 27 , were synthesized starting from bicyclo[3.3.0]oct-1(5)-en-2-one ( 2 ). The key step in the construction of the [3.3.3]-propellane system is an application of the α-alkynone cyclization, namely 3 → 4 and 11 → 14 . The preferred formation of the propellanes 4 and 14 in this step shows that the insertion of the postulated alkylidene carbene intermediate into tertiary C,H-bonds outweighs the one into the secondary ring-C,H-bonds leading to 12/13 and 15/16 , respectively. The two starting materials for the α-alkynone cyclization, 3 and 11 , were prepared from 2 by the reactions shown in Scheme 3. The further elaboration and separation of the cyclization products 4 and 14 to rac-modhephene 1 and its epimer 27 are outlined in Scheme 5.     

The Enantioselective Synthesis of β-Amino Acids,their α-hydroxy derivatives,and the N-terminal components of bestatin and microginin

L -Aspartic acid by tosylation, anhydride formation, and reduction with NaBH₄ was converted into (3S)-3-(tosylamino)butan-4-olide ( 8 ; Scheme 1). Tretment of 8 with ethanolic trimethylsilyl iodide gave the N-protected deoxy-iodo-β-homoserine ethyl ester 9 . The latter, on successive nucleophilic displacement with lithium dialkyl-cuprates ( → 10a–e ), alkaline hydrolysis ( → 11a–e ), and reductive removal of the tosyl group, produced the corresponding 4-substituted (3R)-3-aminobutanoic acids 12a–e (ee > 99%). Electrophilic hydroxylation of 8 ( → 19 ; Scheme 3), subsequent iodo-esterification ( → 21 ; Scheme 4), and nucleophilic alkylation and phenylation afforded, after saponification and deprotection, a series of 4-substituted (2S, 3R)-3-amino-2-hydroxybutanoic acids 24 including the N-terminal acids 24e ( = 3 ) and 24f ( = 4 ) of bestatin and microginin (de > 95%), respectively.     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. III. Ein neues Konzept für die Synthese der enantiomeren Astaxanthine

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. III. A New Concept for the Synthesis of the Enantiomeric Astaxanthins A new and efficient concept for the total synthesis of (3S, 3'S)- and (3R, 3'R)-astaxanthin ( 1a and 1c , resp.) in high overall yield and up to 99,2% enantiomeric purity is described. Key intermediates are the (S)- and (R)-acetals 10 and 17 , respectively (Scheme 2). These chiral building blocks were synthesized via three different routes: a) functionalization of the enantiomeric 3-hydroxy-6-oxo-isophorons⁴) 2 and 11 , respectively (Scheme 2); b) optical resolution of 3,4-dihydroxy-compound⁴) 19 (Scheme 3), and c) fermentative reductions of 6-oxo-isophorone derivatives (Schemes 4 and 5). - The absolute configurations of the two intermediates 12 and 13 (Scheme 2) have been confirmed by X-ray analysis. - The final steps leading to the enantiomeric astaxanthins are identical with those described for optically inactive astaxanthin [1].     

Nucleophilic Addition to CC Bonds,Part X

A mechanistic model is presented for the base‐catalyzed intramolecular cyclization of polycyclic unsaturated alcohols of type A to ethers D (Scheme 1). The alkoxide anion B is formed first in a fast acid‐base equilibrium. For the subsequent reaction to D , a carbanion‐like transition state C is proposed. This mechanism is in full agreement with our results regarding the influence of substituents on the regioselectivity and the rate of cyclization. We studied the effect of alkyl substituents in allylic position (alkylated endocylic olefinic alcohols 1 – 3 ) and, especially, at the exocyclic double bond ( 12 – 15 ). The fastest cyclization (k_rel=1) is 12 → 16 , which proceeds via a primary carbanion‐like transition state ( E : R¹=R²=H). The corresponding processes 13 → 17 and 14 → 17 are characterized by a less‐stable secondary carbanion‐like transtition state ( E : R¹=Me, R²=H, or vice versa) and are slower by a factor of 10⁴. The slowest reaction (k_rel ca. 10⁻⁶) is the cyclization 15 → 18 via a tertiary carbanion‐like transition state ( E : R¹=R²=Me).