Sterospecific Syntheses and Spectroscopic Properties of Isomeric 2,4,6,8-Undecatetraenes. New Hydrocarbons from the Marine Brown Alga Giffordia mitchellae. Part IV.

Giffordene (=(2Z,4Z,6E,8Z)-2,4,6,8-undecatetraene; 9f ) and five steroisomers are new C₁₁H₁₆ hydrocarbons from the marine brown alga Giffordia mitchellae. Their synthesis is based on non-stereoselective Wittig reactions of (E)-2-alkenals with appropriate acetylenic phosphoranes and subsequent chromatographic separation of the resulting (E/Z)-pairs. The uniform enynes (>98% purity) are then stereospecifically reduced to (Z)-alkenes with Zn(Cu/Ag) in aq. MeOH at r.t. ¹³C- and ¹ H-NMR data of the new tetraenes are presented. Biosynthetically, giffordene ( 9f ) originates from dodeca-3,6,9-trienoic acid via an unstable (3Z,5Z,8Z)-1,3,5,8,-undecatetraene followed by a thermally allowed antarafacial 1,7-sigmatropic hydrogen shift to the (2Z,4Z,6E,8Z)-isomer 9f .     

Glycosylidene Carbenes. Part 2. Synthesis of O-Aryl Glycosides

Phenol, 4-methoxyphenol, 4-nitrophenol, methyl orsellinate ( 1 ), and 2,6-di(tert-butyl)-4-methylphenol (BHT; 2 ) have been glycosylated by thermal reaction (20–60°) with various glycosylidene-derived diazirines. 4-Methoxyphenol reacted with the D-glucosylidene-derived diazirine 3 to give O-glucosides ( 4 and 5 , 69%, 3:1) and C-glucosides ( 6 and 7 , 16%, 1:1). Similarly, phenol yielded O-glucosides ( 10 and 11 , 70%, 4:1) and C-glucosides ( 12 and 13 , 13%, 1:1). 4-Nitrophenol gave only O-glycosides, 3 leading to 14 and 15 (75%, 3:2; Scheme 1), and the D-galactosylidene-derived diazirine 17 to 22 and 23 (52% (from 16 ), 65:35; Scheme 2). The reaction of phenol with 17 yielded 58% (from 16 ) of the O-galactosides 18 and 19 (4:1) and 14% of the C-galactosides 20 and 21 (1:1). From the D-mannosylidene-derived diazirine 25 , we predominantly obtained the α-D-configurated 26 (38 % from 24 ). These results are interpreted by assuming that an intermediate (presumably a glycosylidene carbene) first deprotonates the phenol to generate an ion pair which combines to give O- and - with electron-rich phenolates - also C-glycosides. A competition experiment of 3 with 4-nitro- and 4-methoxyphenol gave the products from the former ( 14 and 15 ) and the latter phenol ( 4-7 ) in almost equal amounts. Differences in the kinetic acidity of OH groups, however, may form the basis of a regioselective glycosidation, as evidenced by the reaction of 3 with methyl orsellinate ( 1 ) yielding exclusively the 4-O-monoglycosylated products 27 and 28 (78%, 85:15), although diglycosidation is possible ( 27 → 31 and 32 ; 67%, 4:3; Scheme 3). Steric hindrance does not affect this type of glycosidation; 3 reacted with the hindered BHT ( 2 ) to afford 33 and 34 (81 %, 4:1). The predominant formation of 1,2-trans -configurated O-aryl glycosides is rationalized by a neighbouring-group participation of the 2-benzyloxy group.     

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1-azi-glycoses

In the context of the hypothesis postlating a heterolytic cleavage of a C? N bond during thermolysis of alkoxydiazirines (Scheme 1), we report the preparation of the diazirines 4 , 5 , 7 , and 8 , the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4–9 , and the products of their thermolysis in an aprotic environment. The diazirines 4 , 57 , and 8 (Scheme 2–5) were prepared from the known hemiacetals 10 , 19 , 34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11 , 20 , 35 , and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together with the cyclic hydroxylamine 44 . Oxidation of 11 , 35 , and 43 (N-chlorosuccinimide/1,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO₄) gave good yields of the (Z)-hydroximolactones 12 , 36 , and 45 , while the oxime 20 led to a mixture of the (E)- and (Z)-hydroximolactones 21 and 22 , which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29 , which were obtained, together with 30 , from the reaction of the diazirine 5 with benzaldehyde and PBu₃. Treatment of the hydroximolactone O-sulfonates 13 , 23 , 37 , and 46 with NH₃/MeOH afforded the diaziridines 15 , 25 , 38 , and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4 , 5 , 7 , and 8 , respectively. Thermolysis of the diazirines 1 and 4–9 in MeOH yielded the anomeric methyl glycosides 50/51 , 16/17 , 26/27 , 52/53 , 39/40 , 48/49 , and 54/55 , respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C? N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23° led mostly to the diasteroisomeric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56 , 57 , and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal 59 was obtained in higher yields (18%), together with 44% of 56–58 , by thermolysis of solid 1 . Similarly, thermolysis at higher temperatures of 4 in toluene, THF, or dioxane and of 9 in CH₂Cl₂ or THF yielded the (Z,Z)-lactone azines 60 and 61 , respectively, the latter being accompanied by the dihydro-oxazole 62 .     

A 1H-NMR Spectroscopic Investigation of the Conformation of the Acetamido Group in Some Derivatives of N-Acetyl-D-allosamine and -D-glucosamine

The population of the conformations obtained by rotation around the C(2)? N and the N? C(O) bonds of AllNAc, GlcNAc, and GlcNMeAc derivatives was investigated by ¹H-NMR spectroscopy. The AllNAc-derived α-D -and β-D -pyranosides 4–7 , the AllNAc diazirine 16 , and the GlcNAc-derived axial anomers α-D - 8–10 prefer the (Z)-anti-conformation. A significant population of the (Z)-syn-conformer in the (Z)-syn/(Z)-anti-equilibrium for the equatorial anomers β-D - 8–10 and the GlcNAc diazirine 17 was evidenced by an upfield shift of H? C(2), downfield shifts of H? C(1) and H? C(3), and by NOE measurements. The population of the (Z)-syn-conformation depends on the substituent at C(1) and is highest for the hexafluoroisopropyl glycoside. The population of the (Z)-syn-conformation of β-D - 14 decreases with increasing polarity of the solvent, but a substantial population is still observed for solutions in D₂O. Whereas the α-D -anomers of the hemiacetal 22 and the methyl glycoside 21 prefer the (Z)-anti-conformation in D₂O solution, the corresponding β-D -anomers are mixtures of the (Z)-anti-and (Z)-syn-conformers. The diazirine 17 self-associates in CD₂Cl₂ solution at concentrations above 0.005M at low temperatures. The axial anomers of the GlcNMeAc derivatives α-D - 26–28 are 2:1 to 3:1 mixtures of (Z)-anti-and (E)-anti-conformers, whereas the corresponding β-D -glycosides are ca. 1:3:6 mixtures of (Z)-syn-, (Z)-anti-, and (E)-anti-conformers.     

Photochemie von in 4-Stellung substituierten 5-Methyl-3-phenyl-isoxazolen.44. Mitteilung über Photoreaktionen

Photochemistry of 4-substituted 5-Methyl-3-phenyl-isoxazoles. 4-Trideuterioacetyl-5-methyl-3-phenyl-isoxazole ([CD₃CO]- 27 ), upon irradiation with 254 nm light, was converted into a 1:1 mixture of oxazoles [CD₃CO]- 35 and [CD₃]- 35 (Scheme 13). This isomerization is accompagnied by a slower transformation of ([CD₃CO]- 27 ) into [CD₃]- 27 . Irradiation of the isoxazole derivatives 28, 29, 30 and (E)- 31 yielded only oxazoles 36, 37, 38 and (E), (Z)- 39 ; no 4-acetyl-5-alkoxy-2-phenyl-oxazole, 2-acetyl-3-methyl-5-phenyl-pyrrole or 2-acetyl-4-methoxycarbonyl-3-methyl-5-phenyl-pyrrole, respectively, were formed (Scheme 9 and 10). Similarly (E)- 32 gave a mixture of (E), (Z)- 40 only (Scheme 11). Upon shorter irradiation, the intermediate 2H-azirines (E), (Z)- 41 could be isolated (Scheme 11). Photochemical (E)/(Z)-isomerization of the 2-(trifluoro-ethoxycarbonyl)-1-methyl-vinyl side chain in all the compounds 32, 40 and 41 is fast. At 230° the isoxazoles (E)- and (Z)- 32 are converted into oxazoles (E), (Z)- 40 . The same compounds are also obtained by thermal isomerization of the 2H-azirines (E), (Z)- 41 . The most probable mechanism for the photochemical transformations of the isoxazoles, as exemplified in the case of the isoxazole 27 , is shown in Scheme 13. A benzonitrile-methylide intermediate is postulated for the photochemical conversion of the 2H-azirines into oxazoles. 2H-Azirines are also intermediates in the thermal isoxazole-oxazole rearrangement. It is however not yet clear, if the thermal 2H-azirine-oxazole transformation involves the same transient species as the photochemical reaction. A mechanism for the photochemical isomerization of the 2H-azirine 11 to the oxazole 15 is proposed (Scheme 3).     

Glycosylidene Carbenes. Part 5. Synthesis of Glycono-1,5-lactone Tosylhydrazones as Precursors of Glycosylidene Carbenes

The benzyl- and the acyl-protected glyconolactone tosylhydrazones 6 , 9 , 12 , 16 , and 19 (Scheme 1) were prepared in good yields by treating the hemiacetals 4 , 7 , 10 , 14 , and 17 with N-tosylhydrazine, to give the N-glycosylhydrazines 5 , 8 , 11 , 15 , and 18 , and by oxidizing these hydraz tries with N-bromosuccinimide (NBS) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), with CrO₃–dipyridine complex or with pyridinium dichromate. Photolysis of the sodium sail 20 of 6 (Scheme 2) in the presence of N-phenylmaleimide, dimethyl fumarate, or acrylonitrile gave the corresponding cyctopropanes 21 – 28 in satisfactory yields. Phololytic or thermolytic glycosidation of phenol and 4-melhoxyphenol by 20 yielded the anomeric glycosides 29 / 30 and 31 / 32 , yields being marginally higher for the Ihermolytic process. Phololytic glycosidation of propan-2-ol gave the glycosides 33 and 34 in low yields only. Yields and ratios of products were compared to those obtained with the diazirine 1 as a source of glycosylidene carbenes. While the yields from 20 are lower, the ratios of products obtained in the photolytic reactions are in agreement with the formation of a common intermediate from both carbene precursors.     

Photochemische Reaktionen. 118. Mitteilung [1] Zur vinylogen β-Spaltung von Enonen. UV.-Bestrahlung von 4-(3',7',7'-Trimethyl-2'-oxabicyclo [3.2.0]hept-3'-en-1'-yl)but-3-en-2-on

Vinylogous β-Cleavage of Enones: UV.-irradiation of 4-(3′,7′,7′-trimethyl-2′-oxabicyclo[3.2.0]hept-3′-ene-1′-yl)but-3-ene-2-on On ¹π,π*-excitation (λ = 254 nm) in acetonitrile (E/Z)- 2 is converted into the isomers 4–9 and undergoes fragmentation yielding 10 ; in methanol (E/Z)- 2 gives 7–10 and is transformed into 11 by incorporation of the solvent. On ¹π,π*-excitation (λ λ?347 nm; benzene-d₆) (E)- 2 is isomerized into (Z)- 2 , which is converted into the isomers 3 and 4 by further irradiation. ¹π,π*-Excitation (λ = 254 nm; acetonitrile) of 4 gives 6 and (E)- 9 , whereas UV.-irradiation (λ = 254 nm; acetonitrile-d₃) of 5 yields (E)- 7 and 8 . On ¹π,π*-excitation (λ = 254 nm; acetonitrile) of (E/Z)- 12 the compounds (E)- 14 and (E)- 15 are obtained.     

Glycosylidene Carbenes. Part 15. Synthesis of disaccharides from allopyranose-derived vicinal 1,2-diols. Evidence for the protonation by a H-bonded hydroxy group in the σ-plane of the intermediate carbene,followed by attack on the oxycarbenium ion in the π-plane

The α-D -allo-diol 9 possesses an intramolecular H-bond (HO? C(3) to O? C(1)) in solution and in the solid state (Fig. 2). In solution, it exists as a mixture of the tautomers 9a and 9b (Fig. 3), which possess a bifurcated H-bond, connecting HO? C(2) with both O? C(1) and O? C(3). In addition, 9a possesses the same intramolecular H-bond as in the solid state, while 9b is characterized by an intramolecular H-bond between HO? C(3) and O? C(4). In solution, the β-D -anomer 12 is also a mixture of tautomers, 12a and presumably a dimer. The H-bonding in 9 and 12 is evidenced by their IR and ¹H-NMR spectra and by a comparison with those of 3–8, 10 , and 11 . The expected regioselectivity of glycosidation of 9 and 12 by the diazirine 1 or the trichloroacetimidate 2 is discussed on the basis of the relative degree of acidity/nucleophilicity of individual OH groups, as governed by H-bonding. Additional factors determining the regioselectivity of glycosidation by 1 are the direction of carbene approach/proton transfer by H-bonded OH groups, and the stereoelectronic control of both the proton transfer to the alkoxy-alkyl carbene (in the σ-plane) and the combination of the thereby formed ions (π-plane of the oxycarbenium ion). Glycosidation of 9 by the diazirine 1 or the trichloroacetimidate 2 proceeded in good yields (75–94%) and with high regioselectivity. Glycosidation of 9 and 12 by 1 or 2 gave mixtures of the disaccharides 14–17 and 18–21 , respectively (Scheme 2). As expected, glycosidation of 12 by 1 or by 2 gave a nearly 1:1 mixture of regioisomers and a slight preference for the β-D -anomers (Table 4). Glycosidation of the α-D -anomer 9 gave mostly the 1,3-linked disaccharides 16 and 17 (α-D β-D ) along with the 1,2-linked disaccharides 14 and 15 (α-D < β-D , 1,2-/1,3-linked glycosides ca. 1:4), except in THF and at low temperature, where the β-D -configurated 1,2-linked disaccharide 15 is predominantly formed. Similarly, glycosidation of 9 with 2 yielded mainly the 1,3-linked disaccharides (1,2-/1,3-linked products ca. 1:3 and α-D /β-D ca. 1:4). Yields and selectivity depend upon the solvent and the temperature. The regioselectivity and the unexpected stereoselectivity of the glycosidation of 9 by 1 evidences the combined effect of the above mentioned factors, which also explain the lack of regio-complementarity in the glycosidation of 9 by 1 and by 2 (Scheme 3). THF solvates the intermediate oxycarbenium ion, as evidenced by the strong influence of this solvent on the regio- and stereoselectivity, particularly at low temperatures, where kinetic control leads to a stereoelectronically preferred axial attack of THF on the oxycarbenium ion.     

Glycosylidene Carbenes. Part 24 Reactivity modulation by protecting groups of the addition of glycosylidene carbenes to electron-rich alkenes

The reactivity of glycosylidene carbenes derived from pivaloylated vs. benzylated diazirines 1 and 2 towards enol ethers have been examined. The pivaloylated 1 led to higher yields of spirocyclopropanes than the benzylated 2. Among the enol ethers tested, dihydrofuran 6 proved most reactive, yielding 71–72% of the spiro-linked tetrahydrofuran 7 , while the benzylated diazirine 2 afforded only 33% of the analogue 8 (Scheme 1 ). Other enol ethers proved much less reactive. The addition of 1 and 2 to the dihydropyran 10 and the 2, 3-dihydro-5-methyl-furan 15 gave low yields of single cyclopropanes (→ 12 , 14 , and 16 ), and the glycals 17 and 18 , and (E)-1-methoxy-oct-1-ene ( 23 ) did not react. The main products of these reactions were the azines (Z, Z)- 11 and (Z, Z)/( E, E)- 13. Similarly, 1 and 2 reacted poorly with (Z)-1-methoxyoct-1-ene ( 24 ), leading to cyclopropanes 25 / 26 / 27 and 28 / 29 / 30 / 31 (Scheme 2). Main products were again the azines (Z, Z)- 11 and (Z, Z)/(E, E)- 13 . The structure of 70 and 25 was established by X-ray analysis (Figs. 1 and 2). The mechanism of addition of glycosylidene carbenes to enol ethers is discussed, AMI Calculations indicate that the LUMO_carbene/HOMO_alkoxyalkene interaction is dominant at the beginning of the reaction, while the transition states are characterized by a dominant interaction of the doubly occupied, sp²-hybridized orbital of the carbene with the LUMO of the enol ether. The relative reactivity of the carbenes towards either the enol ethers or the diazirines determine type and yields of the products.     

Studies on the Stereochemistry of 2-(Nitromethylidene)-Heterocycles

The ¹H-NMR spectra of 2-(nitromethylidene)pyrrolidine ( 7 ), 1-methyl-2-(nitromethylidene)imidazolidind ( 10 ) and 3-(nitromethylidene)tetrahydrothiazine ( 11 ) in CDCl₃ and (CD₃)₂SO indicate that these compounds have the intramolecularly H-bonded structures (Z)- 7 , (E)- 10 and (Z)- 11 while the N-methyl derivative 8 of 7 is (E)-configurated in both solvents. 1-Benzylamino-1-(methyltio)-2-nitroehtylene ( 13 ), an acylic model, has the H-bonded configuration (E)- 13 in CDCl₃ and in (CD₃)₂SO. 2-(Nitromethylidene)thiazolidine ( 3 ) has the (E)-configuration in CDCl₃ but exists in (CD₃)₂SO as a mixture of (Z)- and (E)-isomers with the former predominating. Both species are detected to varying proportions in a mixture of the two solvents. ¹⁵N-NMR spectroscopy of 3 ruled out unambiguously the nitronic acid structure 6 and the nitromethyleimine structure 5 . The N-methyl derivative 4 of 3 is (Z)-configurated in (CD₃)₂SO. Comparison of the olefinic proton shifts of (Z)- 3 and (Z)- 4 with those of analogues and also of 1,1-bis(methylti)-2-nitroethylene ( 12 ) shows decreased conjugation of the lone pair of electrons of the ring N-atom in (Z)- 3 and (Z)- 4 . This is also supported by ¹³C-NMR studies. Plausible explanations for the phenomenon are offered by postulating that the ring N-atoms are pyramidal in (Z)- 3 and (Z)- 4 and planar in other cases or, alternatively, that the conjugated nitroenamine system gets twisted due to steric interaction between the NO₂-group and the ring S-atom. Single-crystal X-ray studies of 3 and 8 show that the former exists in the (Z)-configuration and the latter in (E)-configuration; the ring N-atom in the former has slightly more pyramidal character than in the latter.     

Leiopathic Acid,a Novel Optically Active Hydroxydocosapentaenoic Acid,and related compounds,from the black coral Leiopathes sp. of Saint Paul Island (S. Indian Ocean)

The antipatharian Leiopathes sp., collected around Saint Paul Island, is shown here to contain, in relatively high amounts, the novel fatty acid leiopathic acid ( = (+)-(10R,7Z,11E,13Z,16Z,19Z)-10-hydroxy-7,11,13,16,19-docosapentaenoic acid; (+)- 1 ), besides (+)-(8R,5Z,9E,11Z,14Z,17Z)-8-hydroxy-5,9,11,14,17-icosapentaenoic acid ((+)- 11 ) and (+)-(8R,5Z,9E,11Z,14Z,)-8-hydroxy-05,9,11,14-icosatetraenoic acid ((+)- 16 ) and their ethyl ester (+)- 2 , (+)- 12 , and (+)- 17 .     

Glycosylidene Carbenes. Part 6. Synthesis of alkyl and fluoroalkyl glycosides

The syntheses of glycosides from the diazirine 1 and a range of alcohols under thermal and/or photolytic conditions are described. Yields and diastereoselectivities depend upon the pK_HA values of the alcohols, the solvent, and the reaction temperature. The glycosidation of weakly acidic alcohols (MeOH, EtOH, i-PrOH, and t-BuOH, 1 equiv. each) in CH₂Cl₂ at room temperature leads to the glycosides 2–5 in yields between 60 and 34% (Scheme 1 and Table 1). At ?70 to ?60°, yields are markedly higher. In CH₂Cl₂, diastereoselectivities are very low. In THF, at ?70 to ?60°, however, glycosidation of i-PrOH leads to α-D -/β-D - 4 in a ratio of 8:92. More strongly acidic alcohols, such as CF₃CH₂OH, (CF₃)₂ CHOH, and (CF₃)₂C(Me)OH, and the highly fluorinated long-chain alcohols CF₃(CF₂)₅(CH₂)₂OH ( 11 ) and CHF₂(CF₂)₉CH₂OH ( 13 ) react (CH₂Cl₂, r.t.) in yields between 73 and 85% and lead mainly to the β-D -glucosides β-D - 6 to β-D - 8 , β-D - 12 , and β-D - 14 (d.e. 14–68%). Yields and diastereoselectivities are markedly improved, when toluene, dioxane, 1,2-dimetoxyethane, or THF are used, as examined for the glycosidation of (CF₃)₂C(Me)OH, yielding (1,2-dimethoxyethane, 25°) 80% of α-D -/ β-D - 8 in a ratio of 2:98 (d.e. 96%; Table 4). In EtCN, (CF₃)₂C(Me)OH yields up to 55% of the imidate 10 . Glycosidation of di-O-isopropylideneglucose 15 leads to 16 (CH₂Cl₂, r.t.; 65%, α-D / β-D = 33:67). That glycosidation occurs by initial protonation of the intermediate glycosylidene carbene is evidenced, for strongly acidic alcohols, by the formation of 10 , derived from the attack of (CF₃)₂MeCO^? on an intermediate nitrilium ion (Scheme 4), and for weakly acidic alcohols, by the formation of α-D - 9 and β-D - 9 , derived by attack of i-PrO^? on intermediate tetrahydrofuranylium ions. A working hypothesis is presented (Scheme 3). The diastereoselectivities are rationalized on the basis of a protonation in the σ plane of the intermediate carbene, the stabilization of the thereby generated ion pair by interaction with the BnO? C(2) group, with the solvent, and/or with the alcohol, and the final nucleophilic attack by RO^? in the π plane of the (solvated) oxonium ion.     

Azimine. V.. Untersuchungen zur stereoisomerie an der N(2), N(3)-bindung von 2, 3-dialkyl-1-phthalimido-aziminen

Azimines. V. Investigation on the Stereoisomerism Around the N (2), N (3) Bond in 2, 3-Dialkyl-1-phthalimido-azimines 2, 3-(cis-1, 3-Cyclopentylene)-1-phthalimido-azimine ( 7 ) and isomerically pure (2 Z)- and (2 E)-2, 3-diisopropyl-1-phthalimido-azimine ( 9a and 9b ) were prepared by the addition of phthalimido-nitrene ( 1 ) to 2, 3-diazabicyclo [2.2.1]hept-2-ene ( 6 ) and to (E)- and (Z)-1, 1′-dimethylazoethane ( 8a and 8b ), respectively. Comparison of their UV. spectra with those of two stereoisomeric azimines of known configuration, namely (1 E, 2 Z)- and (1 Z, 2 E)-2, 3-dimethyl-1-phthalimido-azimine ( 5a and 5b ), reveals that 2, 3-dialkyl-1-phthalimido-azimines with (2 Z)-configuration are characterized by a shoulder at about 258 nm (? ≈? 14,000) and those with (2 E)-configuration by a maximum at 270–278 nm (? ≈? 10,000). The (2 E)-azimine 9b isomerizes under acid catalysis as well as thermally and photochemically into the more stable (2 Z)-isomer 9a . Under the last two conditions the isomerization is accompanied by a slower fragmentation with loss of nitrogen into N, N′-diisopropyl-N, N′-phthaloylhydrazine ( 4 , R = iso-C₃H₇). The same fragmentation was also observed on thermolysis and photolysis of the (2 Z)-isomer 9a . The kinetic parameters for the thermal isomerization of 9b (they fit first-order plots) and for the fragmentation of 9a and 9b were determined by ¹H-NMR. spectroscopy in benzene, trichloromethane and acetonitrile. In the photolysis of 9a or 9b the fragmentation is accompanied by dissociation into the azo compounds 8a or 8b and the nitrene 1 , the latter being subject to trapping by cyclohexene. With the azimine 7 , an analogous thermal fragmentation was observed to give N, N′-(cis-1, 3-cyclo-pentylene)-N, N′-phthaloylhydrazine ( 15 ), but more energetic conditions were required than with 9 . Photolysis of 7 led exclusively to dissociation into the azo compound 6 and the nitrene 1 , perhaps because the fragmentation of 7 is prevented by ring strain.     

Glycosylidene Carbenes. Part 17. Glycosidation of benzyl β-D- and β-L-ribopyranosides. Further evidence for the effect of stereoelectronic control on the regioselectivity of glycosidation

The H-bonds of the enantiomeric ribosides 4 and 5 and their glycosidation by the diazirine 1 are described. HO–C(2) and HO? C(4) of 4 and 5 form a ‘flip-flop’ H-bonding system, with HO? C(3) acting as a H-bond donor to O? C(2) or O? C(4). HO? C(2) and HO? C(4) of monomeric 4 and 5 are thus the most strongly acidic OH groups. Glycosidation of 4 and 5 by 1 depends on the solvent, the temperature, and the concentration. It yields up to 91% of a mixture of anomeric pairs of the 1,2-, 1,3-, and 1,4-linked disaccharides 8–13 and 20–25 , respectively, which were characterized as their diacetates 14–19 and 26–31 (Scheme). Glycosidation in CH₂Cl₂ and in dioxane yielded mostly the 1,3-linked disaccharides 10/11 and 22/23 (α/β ca. 4:1), while glycosidation in THF leads mostly to the 1,2- and 1,4-linked regioisomers (β>α). There are small, but significant differences in the glycosidation of 4 and 5 . These, the regio-, and the stereoselectivities are rationalized as the consequences of the stereoelectronic control of both the H-transfer from HO? C(2) or HO? C(4) to the intermediate carbene and of the formation of the glycosidic C? O bond, and of the coordination of the intermediate oxycarbenium ion with THF.     

Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K1

Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K₁ The Li₂CuCl₄-catalyzed couplings of the easily accessible bifunctional C₅ allylic acetates (E)- 18a and (E)- 18b with racemic hexahydrofarnesylmagnesium bromide ((3 RS/RS, 7 RS/SR)- 19a ) proceed with high chemo- and stereoselectivity (≥98% (E)-retention) to give the (2E, 7 RS/RS, 11 RS/SR)-phytol derivatives 1a and 1b , respectively, in yields of 72–80% (Scheme 5). The same couplings performed with optically active hexahydrofarnesylmagnesium bromide (3 R, 7 R)- 19a yielded the (E)-phytol derivatives of the natural series (7 R, 11R)- 1a and (7 R, 11 R)- 1b. Acid-catalyzed hydrolysis of(2 E, 7 R, 11 R)- 1b gave natural phytol((2 E, 7 R, 11 R)- 1c ) Friedel-Crafts alkylation of ‘menadiol monobenzoate’ 11b with (2 E, 7 R, 11 R)- 1a or (2 E, 7 R, 11 R)- 1b gave the dihydrovitamine K₁ derivative (2 E/Z, 7′ R, 11′R)- 12b ((E/Z)≈? 9:l). Conversion of configurationally pure (2 E, 7′ R, 11′ R)- 12b (yield 73%; obtained after chromatographic removal of the (Z)-isomer) into natural vitamine K₁ ((2 E,7′ R, 11′ R)- 2 ) was achieved in the usual way by saponification and oxidation with air. Some further investigations of the coupling reactions of bifunctional C₅ allylic synthons with hexahydrofarnesylmagnesium bromide (3 RS/RS, 7 RS/SR)- 19a showed the outcome of these reactions to be critically dependent on the nature of the leaving group, the double-bond geometry and the nature and concentration of the catalyst. Thus, the Li₂CuCl₄-catalyzed couplings of (3 RS/RS,7 RS/SR)- 19a with the allylic halides 29a and 29c as well as with p-toluenesulfonate 29b yielded besides the phytol derivatives 1a and 1b - also the S_N2′-type products 30a and 30b (Scheme 8, Table 2); the same result was found for the coupling with the cis-configurated allylic acetates (Z)- 18a and (Z)- 18b (Table 3). A similar loss of chemo selectivity as well as the loss of stereoselectivity in the coupling reactions of 19 with the bifunctional (E)-olefins of type 18 was observed when the Li₂CuCl₄-catalyst concentration was increased from 0.2 to 25 mol-% or upon substitution of Li₂CuCl₄ by copper (I) chloride or iodide (Table 4).     

Synthese von bromosubstituierten Butenoliden II

Synthesis of Bromosubstituted Butenolides II . Methyl 4,4′-dibromosenecioate ( 2 ) was prepared by double N-bromosuccinimide bromination of methyl senecioate ( 1 ) and converted to methyl 4,4′-diiodo-senecioate ( 3 ) with sodium iodide and to 3-bromomethyl-2-buten-4-olide ( 4 ) with aqueous hydrobromic acid. A mixture of methyl (Z)- and (E)-4-bromosenecioate ( 8 and 9 ) yielded 3-methyl-2-butenolide ( 5 ) with aqueous hydrobromic acid and a mixture of (Z)-and (E)-4-methoxy-senecioic acid ( 10 and 11 ) with methanolic potassium hydroxide. N-Bromosuccinimide treatment of the butenolide 5 afforded 4-bromo-3-methyl-2-buten-4-olide ( 6 ) and 4,4-dibromo-3-methyl-2-buten-4-olide ( 7 ).     

Chiral [2H]-Labelled Methylene Groups in Trienoic- and Dienoic Fatty Acids: A Facile Approach via Asymmetric Epoxidation of [2H] Allyl Alcohols

Chiral [²H] -labelled methylene groups flanked by two double bonds within (poly)unsaturated fatty acids are readily available from trans-2,3-epoxy[2,3-²H₂] alk-4-yn-l-ols, obtained in their turn by asymmetric epoxidation of the corresponding (E)-[2,3-²H₂] alk-2-en-4-yn-l-ols (see Scheme 3). The procedure is exemplified for (8S,3Z,6Z,9Z)-[7,8-²H₂] trideca-3,6,9-trienoic acid ((8S)- 11 ) and (8R)- 11 (Scheme 4) as well as for (5S,3Z,6Z)-[4,5^?2H₂]deca-3,6-dienoic acid ((5S)- 13 ) and (5R)- 13 (Scheme 5).     

Photochemical reactions. 137th communication. Preparation and photolysis of (E/Z)-7-methyl-β-ionone

The title compounds (E/Z)- 7 were prepared in 66% overall yield by reaction of β-ionone ((E)-( 1 ) with lithium dimethylcuprate, trapping of the intermediate enolate with benzeneselenenyl bromide and oxidation with H₂O₂. Analogously, (E/Z)-7-methyl-α-inone ((E/Z)- 12 ) was obtained in 65% yield from α-ionone ((E)- 11 ). ¹n, π^*- Excitation (λ > 347 nm, pentane) of (E)-7 causes rapid (E/Z)-isomerization and subsequent reaction of (Z)- 7 to 15 (66%). The formation of 15 is explained by twisting of the dienone chromophore due to repulsive interaction of the 7-CH₃-group with the CH₃-groups of the cyclohexene ring. On the other hand, irradiation λ > 347 nm, Et₂O) of (E)- 7 in the presence of acid leads to (Z)- 7 (5%) and to the novel compound 16 (88%).     

Photochemische Reaktionen 111. Mitteilung [1] Zur Photochemie α, β-ungesättigter γ, δ-Epoxyester I: Singulett- versus Triplettreaktivität

On triplet excitation (E)- 2 isomerizes to (Z)- 2 and reacts by cleavage of the C(γ), O-bond to isomeric δ-ketoester compounds ( 3 and 4 ) and 2,5-dihydrofuran compounds ( 5 and 19 , s. Scheme 1). - On singulet excitation (E)- 2 gives mainly isomers formed by cleavage of the C(γ), C(δ)-bond ( 6–14 , s. Scheme 1). However, the products 3–5 of the triplet induced cleavage of the C(γ), O-bond are obtained in small amounts, too. The conversion of (E)- 2 to an intermediate ketonium-ylide b (s. Scheme 5) is proven by the isolation of its cyclization product 13 and of the acetals 16 and 17 , the products of solvent addition to b . - Excitation (λ = 254 nm) of the enol ether (E/Z)- 6 yields the isomeric α, β-unsaturated ε-ketoesters (E/Z)- 8 and 9 , which undergo photodeconjugation to give the isomeric γ, δ-unsaturated ε-ketoesters (E/Z)- 10 . - On treatment with BF₃O(C₂H₅)₂ (E)- 2 isomerizes by cleavage of the C(δ), O-bond to the γ-ketoester (E)- 20 (s. Scheme 2). Conversion of (Z)- 2 with FeCl₃ gives the isomeric furan compound 21 exclusively.     

Stereoselective Synthesis of Isomers of the Naturally Occurring 13-Hydroxy-2,4,9-tetradecatrienoic Acid. Part II [1]

The stereoselective syntheses of four unsaturated hydroxy fatty acids 13S,2E,4E,9E)- 13-hydroxy-2,4,9-tetradecatrienoic acid, (13S,9Z,11E)-13-hydroxy-9,11-tetradecadienoic acid, (13S,9E, 11E)-13-hydroxy-9,11-tetradecadienoic acid, and (13S,2E,4E,9E)-13-hydroxy-2,4,9,11-tetradecatrienoic acid, are described. Wittig reactions, regioselective oxidation of dialcohol 3, and diastereomerization were used.