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.     

Glyconothio-O-lactones. Part I. Preparation and reactions with nucleophiles

Furanoid and pyranoid glyconothio-O-lactones were prepared by photolysis of S-phenacyl thioglycosides or by thermolysis of S-glycosyl thiosulfinates, which gave better results than the thionation of glyconolactones with Lawesson's reagent. Thermolysis of the thiosulfinates obtained from the dimannofuranosyl disulfide 7 or the manofuranosyl methly disulfide 8 (Scheme 2) gave low yields of the thio-O-lactone 2 . However, photolysis of the S-phenacyl thioglycoside 6 obtained by in situ alkylation of the thiolato anion derived from 5 led in 78–89% to 2 . Similarly, the dithiocarbonate 10 was transformed, via 11a , into the ribo-thio-O-lactone 12 (79%). Thermolysis of the peracetylated thiosulfinates 14 (Scheme 3) led to the intermediate thio-O-lactone 15 , which underwent facile β-elimination of AcOH (→ 16 , 75%) during chromatography. The perbenzylated S-glucopyranosyl dithiocarbonate 18 (Scheme 4) was transformed either into the S-phenacyl thioglucoside 19 or into a mixture of the anomeric methyl disulfides 21a/b . Whereas the photolysis of 19 led in moderate yield to 2-deoxy-thio-O-lactone 20 , oxidation of 21b and thermolysis of resulting thiosulfinates gave the thio-O-lactone 4 (79%), which was transformed into 20 (36%) upon photolysis. The pyranoid manno-thio-O-lactone 26 was prepared in the same way and in good yields from 22 via the dithiocarbonate 24b and the disulfide 25 . The ring conformations of the δ-thio-O-lactones, flattened ⁴C₁ for 15 and 4 and B_2,5 for 26 , are similar to the ones of the O-analogous oxo-glyconolactones. The reaction of 2 (Scheme 5) with MeLi and then with MeI gave the thioglycoside 27 (29%) and the dimeric thio-O-lactone 29 (47%). The analogous treatment of 2 with lithium dimethylcuprate (LiCuMe₂) and MeI led to a 4:1 mixture (47%) of 31 and 27 . The structure of 2 was proven by an X-ray analysis, and the configuration at C(6) and C(5) of 29 was deduced from NOE experiments. Substitution of MeI by CD₃I led to the CD₃S analogues of 27 , 29 , and 31 , i.e. 28 , 30 , and 32 , respectively, evidencing carbophilic addition and ‘exo’-attack on 2 by MeLi and the enethiolato anion derived from 2 . The preferred ‘endo’-attack of LiCuMe₂ is rationalized by postulating a single-electron transfer and a diastereoselective pyramidalization of the intermediate radical anion.     

Glycosylidene Carbenes a new approach to glycoside synthesis. Part 1. Preparation of glycosylidene-derived diaziridines and diazirines

A new approach towards the synthesis of glycosides based upon a (formal) insertion of glycosylidene carbenes into O? H bonds is presented. The synthesis and characterization of the glycosylidene-derived diazirines 25 – 28 , precursors of glycosylidene carbenes, are described. The diazirines were prepared by the rapid, high-yielding oxidation of the diaziridines 20 and 22 – 24 with I₂/Et₃N. The diaziridines, the first examples of C- alkoxy-diaziridines, were formed in high yields by the reaction of the [(glycosylidene)-amino]methanesulfonates 14 and 17 – 19 with a saturated solution of NH₃ in MeOH. The diazirines are highly reactive compounds, losing N₂ at room temperature or below. The reaction of the gluco-configurated diazirine 25 with i-PrOH yielding a mixture of the α- and β-D -glucosides 29 and 30 illustrates the potential of glycosylidene-derived diazirines as a new type of glycosyl donors.     

Glycosylidene Carbenes. Part 4. Synthesis of Spirocyclopropanes from Acetamidoglycosylidene-Derived Diazirines

The synthesis of the first glycosylidene-derived 2-acetamido-2-deoxydiazirine 4 from N-acetylglucosamine 6 is described. Thus, 6 was transformed into the 3-O-mesylglucopyranoside 9 by glycosidation with allyl alcohol, benzylidenation, and mesylation (Scheme 2). Solvolysis of 9 gave the allopyranoside 10 which, upon benzylation and glycoside cleavage, yielded the hemiacetals 12 . Using our established method (via the lactone oxime 14 and the diaziridines 16 ), 12 gave the diazirine 4 . Thermolysis of this diazirine in the presence of i-PrOH gave the dihydro-1,3-oxazole 5 (Scheme 1); in the presence of acrylonitrile, the four diastereoisomeric spirocyclopropanes 17–20 and the acetamidoallal 21 were obtained and separated by prep. HPLC (Scheme 3). Assignment of the configuration of 17–20 is based on NOE measurements and on the effect of diamagnetic anisotropy of the CN group. The ratio of the four cyclopropanes, which is in keeping with earlier results, is rationalized.     

Glyconothio-O-lactones. Part III. Thermolysis of a 4,5-Dihydro-1,2,3- and a 2,5-Dihydro-1,3,4-thiadiazole

Addition of CH₂N₂ to 2,3:5,6-di-O-isopropylidene-1-thio-mannono-1,4-lactone ( 1 ) gave the 2,5-dihydro-1,3,4-thiadiazole 2 and the 4,5-dihydro-1,2,3-thiadiazole 3 . First-order kinetics were observed for the thermolysis of 3 (Scheme 3) at 80–110° in C₆D₅Cl solution and of 2 (Scheme 3) at 20–35° in CDC1₃, respectively. The 1,2,3-thiadiazole 3 led to mixtures of the thiirane 9 , the starting thionolactone 1 , the thiono-1,5-lactone 8 , and the enol ether 7 , while the isomeric 1,3,4-thiadiazole 2 led to mixtures of the anomeric thiiranes 9 and 12 , the O-hydrogen S,O,O-ortholactone α-D - 14 , the S-methyl thioester 15 , the S,S,O-ortholactone 13 , and the 2,3:5,6-di-Oisopropylidene-mannono-1,4-iactone ( 16 ). Pure products of the thermolysis were isolated by semipreparative supercritical fluid chromatography (SFC), whereas preparative HPLC led to partial or complete decomposition. Thus, the β-D -mannofuranosyl β-D -mannofuranoside 10 , contaminated by an unknown S species, was isolated by preparative HPLC of the crude product of thermolysis of 3 at 115–120° and partially transformed in CD₃OD solution into the symmetric di(α-D -mannofuranosyl) tetrasulfide 11 . Its structure was evidenced by X-ray analysis. Similarly, HPLC of the thermolysis product of 2 gave the enethiol 17 , the sulfide 19 , and the mercapto alcohol 18 as secondary products. Thermolysis of the thiirane 9 at 110–120° (Scheme 4) led to the anomeric thiirane 12 which was transformed into mixtures of the enethiol 17 and the enol ether 7. Addition of H₂O to 17 and 7 gave the corresponding hemiacetals 18 and 20. The mechanism of the thermolysis of the dihydrothiadiazoles 2 and 3 , and the thiiranes 9 and 12 is discussed.     

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).     

Singlet-Oxygen Ene Reactions of (E)-4-Propyl[1,1,-2H3]oct-4-ene. Short Communication

Rose bengal-sensitized photooxygenation of 4-propyl-4-octene ( 1 ) in MeOH/Me₂CHOH 1:1 (v/v) and MeOH/H₂O 95:5 followed by reduction gave (E)-4-propyl-5-octen-4-ol ( 4 ), its (Z)-isomer 5 , (E)-5-propyl-5-octen-4-ol ( 6 ), and its (Z)-isomer 7 . Analogously, (E)-4-propyl[1,1,1-²H₃]oct-4-ene ( 2 ) gave (E)-4-propyl[1,1,1-²H₃]oct-5-en-4-ol ( 14 ), its (Z)-isomer 15 , (E)-5-[3′,3′,3′-²H₃]propyl-5-octen-4-ol ( 16 ), its (Z)-isomer 17 , and the corresponding [8,8,8-²H₃]-isomers 18 and 19 (see Scheme 1). The proportions of 4–7 were carefully determined by GC between 10% and 85% conversion of 1 and were constant within this range. The labeled substrate 2 was photooxygenated in two high-conversion experiments, and after reduction, the ratios 16/18 and 17/19 were determined by NMR. Isotope effects in 2 were neglected and the proportions of corresponding products from 1 and 2 assumed to be similar (% 4 ≈? % 14 ; % 5 ≈? % 15 ; % 6 ≈? % ( 16 + 18 ): % 7 ≈? % ( 17 + 19 )). Combination of these proportions with the ratios 16/18 and 17/19 led to an estimate of the proportions of hydroperoxides formed from 2 . Accordingly, singlet oxygen ene additions at the disubstituted side of 2 are preferred (ca. 90%). The previously studied trisubstituted olefins 20–25 exhibited the same preference, but had both CH₃ and higher alkyl substituents on the double bond. In these substrates, CH₃ groups syn to the lone alkyl or CH₃ group appear to be more reactive than CH₂ groups at that site beyond a statistical bias.     

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.     

Thermische (E), (Z)-Isomerisierungen bei substituierten Propenylbenzolen

Thermal (E), (Z)-Isomerizations of Substituted Propenylbenzenes The thermal isomerizations of (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)phenol ((E)- and (Z)- 3 ), (E)- and (Z)-N-methyl-2-(1′-propenyl)anilin ((E)- and (Z)- 4 ), (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)anilin ((E)- and (Z)- 5 , (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z- 6 ), (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z)- 7 ), (E)- and (Z)-2-(1′-propenyl)toluene ((E)- and (Z)- 8 ), (E)- and (Z)-4-(1′-propenyl)toulene ((E)- and (Z)- 9 ) as well as of (E)- and (Z)-2-(2′-butenyl)-mesitylene ((E)- and (Z)- 10 ) in decane solution were studied (Scheme 2). Whereas the isomerization of the 2-propenylphenols (E)- and (Z)- 3 occurs already between 130 and 150° (cf. Table 1), the isomerization of the 2-propenylanilins 4 and 5 takes place only at temperatures between 220 and 250° (cf. Tables 2 and 3). The activation values and the experiments using N-deuterated 4 (cf. Scheme 4) show that 2-propenylphenols and -anilins isomerize via sigmatropic [1,5]-hydrogen-shifts. For the isomerization of the methyl-substituted propenylbenzenes temperatures > 360° are required (cf. Tables 4 and 5). The activation values of the isomerization of (E)- and (Z)- 6 and (E)- and (Z)- 9 are in accord with those of other (E), (Z)-isomerizations which occur via vibrationally excited singlet biradicals (cf. Table 7). Nevertheless, thermal isomerization of 2′-d-(Z)- 8 (cf. Scheme 6) demonstrates that during the reaction deuterium is partially transfered into the ortho-methyl group, i.e. 1,5-hydrogen-shifts must have participated in isomerization of (E)- and (Z)- 8 (cf. Scheme 8). Under the equilibrium conditions 2,4,6-trimethylindan ( 17 ) is formed slowly at 368° from (E)- and (Z)- 6 , very probably via a radical 1,4-hydrogen-shift (cf. Scheme 9). In a similar way 2-ethyl-4,6-dimethylindan ( 19 ; cf. Table 6) arises from (E)- and (Z)- 7 . Thermolysis of (E)- and (Z)- 10 in decane solution at 367° results in almost no (E),(Z)-isomerization. At prolonged heating 19 and 2,5,7-trimethyl-1,2,3,4-tetrahydronaphthalene ( 20 ) are formed; these two products arise very likely from an intermolecular radical process (cf. Scheme 10).     

Glycosylidene Carbenes. Part 31

The diastereoselectivity of the addition of NH₃ and MeNH₂ to glyconolactone oxime sulfonates and the structures of the resulting N‐unsubstituted and N‐methylated glycosylidene diaziridines were The ¹⁵N‐labelled glucono‐ and galactono‐1,5‐lactone oxime mesylates 1* and 9* add NH₃ mostly axially (>3 : 1; Scheme 4), while the ¹⁵N‐labelled mannono‐1,5‐lactone oxime sulfonate 19* adds NH₃ mostly equatorially (9 : 1; Scheme 7). The ¹⁵N‐labelled mannono‐1,4‐lactone oxime sulfonate 30* adds NH₃ mostly from the exo side (>4 : 1; Scheme 9). The configuration of the N‐methylated pyranosylidene diaziridines 17, 18, 28 , and 29 suggests that MeNH₂ adds to 1, 9, 19 , and 23 mostly to exclusively from the equatorial direction (>7 : 3; Schemes 5 and 8). The mannono‐1,4‐lactone oxime sulfonate 30 adds MeNH₂ mostly from the exo side (85 : 15; Scheme 10), while the ribo analogue 37 adds MeNH₂ mostly from the endo side (4 : 1; Scheme 10). Analysis of the preferred and of the reactive conformers of the tetrahedral intermediates suggests that the addition of the amine to lactone oxime sulfonates is kinetically controlled. The diastereoselectivity of the diaziridine formation is rationalized as the result of the competing influences of intramolecular H‐bonding during addition of the amines, steric interactions (addition of MeNH₂), and the kinetic anomeric effect. The diaziridines obtained from 2,3,5‐tri‐O‐benzyl‐D ‐ribono‐ and ‐D ‐arabinono‐1,4‐lactone oxime methanesulfonate ( 42 and 48 ; Scheme 11) decomposed readily to mixtures of 1,4‐dihydro‐1,2,4,5‐tetrazines, pentono‐1,4‐lactones, and pentonamides. The N‐unsubstituted gluco‐ and galactopyranosylidene diaziridines 2, 4, 6, 8 , and 10 are mixtures of two trans‐substituted isomers ( S / R ca. 19 : 1, Scheme 2). The main, (S,S)‐configured isomers S are stabilised by a weak intramolecular H‐bond from the pseudoaxial NH to RO? C(2). The diaziridines 12 , derived from GlcNAc, cannot form such a H‐bond; the (R,R)‐isomer dominates ( R / S 85 : 15; Scheme 3). The 2,3‐di‐O‐benzyl‐D ‐mannopyranosylidene diaziridines 20 and 22 adopt a ⁴C₁ conformation, which does not allow an intramolecular H‐bond; they are nearly 1 : 1 mixtures of R and S diastereoisomers, whereas the ^OH₅ conformation of the 2,3:5,6‐di‐O‐isopropylidene‐D ‐mannopyranosylidene diaziridines 24 is compatible with a weak H‐bond from the equatorial NH to O? C(2); the (R,R)‐isomer is favoured ( R / S ≥7 : 3; Scheme 6). The mannofuranosylidene diaziridine 31 completely prefers the (R,R)‐configuration (Scheme 9).     

Glycosylidene Carbenes. Part 22. α-D-Selectivity in the Glycosidation by Carbenes Derived from 2-Acetamido-hexoses

Glycosylidene carbenes derived from the GlcNAc and AllNAc diazirines 1 and 3 were generated by the thermolysis or photolysis of the diazirines. The reaction of 1 with i-PrOH gave exclusively the isopropyl α-D -glycoside of 5 besides some dihydrooxazole 9 (Scheme 2). A similar reaction with (CF₃)₂CHOH yielded predominantly the α-D -anomer of 6 , while glycosidation of 4-nitrophenol (→ 7 ) proceeded with markedly lower diastereoselectivity. Similarly, the Allo-diazirine 3 gave the corresponding glycosides 12–14 , but with a lower preference for the α-D -anomers (Scheme 3). The reactions of the carbene derived from 1 with Ph₃COH (→ 8 ) and diisopropylideneglucose 10 (→ 11 ) gave selectively the α-D -anomers (Scheme 2). The αD -selectivity increases with increasing basicity (decreasing acidity) of the alcohols. It is rationalized by an intermolecular H-bond between the acetamido group and the glycosyl acceptor. This H-bond increases the probability for the formation of a 1,2-cis-glycosidic C–O bond. The gluco-intermediates are more prone to forming a N–H…?(H)OR bond than the allo-isomers, since the acetamido group in the N-acetylallosamine derivatives forms an intramolecular H-bond to the cis-oriented benzyloxy group at C(3), as evidenced by δ/T and δ/c experiments.     

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 .     

New Insights on the Mechanism of Thermal Cleavage of Unsaturated Bicyclic Diaziridines: A DFT Study

A DFT calculations are carried out at UB3LYP/6‐311++G (3df, 2p) levels of theory to study electrocyclic thermal cleavage of four (R) derivatives of unsaturated bicyclic diaziridines, 1_X‐R , to produce corresponding (Z) and (E) azomethine imides ( 2_X‐Z , 2_X‐E , 3_X‐Z and 3_X‐E ), where X=H, Me, t‐Bu and Ph. Cleavage of 1_X‐R series to form the most stable 3_X‐Z product, (path 2) is found the favored procedure because of delocalized negative charge on five atoms and lower steric effect in related transition state. According to IRC calculations in paths 1 and 2, C⁶ N¹ bond is cleaved before the rate determinating step (transition state). The stability of unsaturated bicyclic diaziridines and their corresponding (Z) and (E) azomethine imides is in the following order in gas phase and chloroform, tetrahydrofuran, and acetone solvents: 3_X‐Z < 3_X‐E < 2_X‐Z < 2_X‐E < 1_X‐R < 1_X‐S .     

Biosynthesis of δ-Jasmin Lactone ( = (Z)-Dec-7-eno-5-lactone) and (Z,Z)-Dodeca-6,9-dieno-4-lactone in the Yeast Sporobolomyces odorus

(all-Z)-(9,10,12,13,15,16-²H₆)Octadeca-9,12,15-trienoic acid ( = α-linolenic acid; D₆- 4 ) was synthesized to investigate the biochemical formation of linolenic-acid-derived aroma compounds in cultures of the yeast Sporobolomyces odorus, using an established gas chromatographic/mass spectrometric (GC/MS) method. Three compounds were identified as labeled: (Z)-dec-7-eno-5-lactone (δ-jasmin lactone), (Z,Z)-dodeca-6,9-dieno-4-lactone, and (2E,4Z)-hepta-2,4-dienoic acid. Both lactones were biosynthesized mostly under conservation of the initial configuration from their corresponding oxygenated linolenic-acid intermediates. The application of (13S,9Z,11E,15Z)-13-hydroxy(9,10,12,13,15, 16-²H₆)octadeca-9,11,15-trienoic acid (D₆- 7 ) as a OH-functionalized precursor of δ-jasmin lactone allowed to gain insight into the stereochemical course of the biosynthesis to both enantiomers of this lactone. In this experiment, 88.3% of the metabolized labeled precursor was transformed under retention of the original configuration of the (R)-enantiomer. This investigation is also a contribution to a better understanding of the C?C bond isomerization steps which took place during the β-oxidative degradation of the substrate.     

Glycosylidene Carbenes. Part 7. Neighbouring-group participation by the 2-benzyloxy group in the glycosidation of strongly acidic hydroxy compounds

To demonstrate the neighbouring-group participation of the 2-benzyloxy group in the glycosidation of phenols and of strongly acidic alcohols by the diazirine 1 , we examined the glycosidation of 4-nitrophenol, 4-methoxyphenol, (CF₃)₂CHOH, MeOH, and i-PrOH by the diazirine 11 , derived from the 2-deoxypyranose 6 . Oxidation of the oximes 7 yielded (E)- and (Z)- 8 . In solution, (E)- 8 isomerised to (Z)- 8 . Similarly, the (E)-configurated mesylate 9 , prepared from 8 , underwent acid-catalysed isomerisation to (Z)- 9 . Treatment of (Z)- 9 with NH₃, followed by oxidation of the resulting diaziridine 10 with I₂, yielded the desired diazirine 11 . Glycosidation by 11 of the above mentioned hydroxy compounds yielded the glycosides 12–21 . In agreement with the postulated neighbouring-group participation, these glycosidation proceeded without, or with a very low diastereoselectivity, favouring the axial anomers.     

Caulerpenyne-Amine Reacting System as a Model for in vivo Interactions of Ecotoxicologically Relevant Sesquiterpenoids of the mediterranean-adapted tropical green seaweed caulerpa taxifolia

Caulerpenyne ( 1 ), the most abundant of the ecotoxicologically relevant sesquiterpenoids of the Mediterranean-adapted tropical green seaweed Caulerpa taxifolia, was found to react with Et₃N or pyridine in MeOH by initial deprotection of C(1)HO to give oxytoxin 1 ( 2a ), previously isolated from the sacoglossan mollusc Oxynoe olivacea. With BuNH₂, without any precaution to exclude light, 1 gave the series of racemic 3 and 4 , and achiral (4E,6E)- 5 , (4E,6Z)- 5 , (4Z,6E)- 5 , and (4Z,6Z)- 5 pyrrole compounds, corresponding to formal C(4) substitution, 4,5-β-elimination, and (E/Z)-isomerization at the C(4)?C(5) and C(6)?C(7) bonds. Changing to CDCl₃ as solvent in the dark, 1 gave cleanly, via 2a as an intermediate, 3 and (4E,6E)- 5 . The latter proved to be prone to (E/Z)-photoisomerization. Under standard acetylation conditions, 3 gave (4E,6E)- 5 via acetamide 7 as an intermediate. Particular notice is warranted by selective deprotection of 1 at C(1), mimicking enzyme reactions, and unprecedented formation of pyrrole compounds from freely-rotating, protected 1,4-dialdehyde systems.     

Introduction of Amino Alcohols in the Ring-Opening Reaction of 3-bromo-2,5-dimethylthiophene 1,1-dioxide. A short diastereoselective synthesis of substituted ‘tetrahydrobenzo[a]pyrrolizidines’ (= octahydro-1H-pyrrolo[2,1-a]isoindoles) using L-prolinol

Tetrahydrobenzo[a]pyrrolizidines (= octahydro-1H-pyrrolo[2,1-a]isoindoles) and tetrahydrobenzo[a]indo-lizidines, (= decahydropyrido[2,1-a]isoindoles) were prepared stereoselectively in four steps through an amineinduced ring-opening of 3-bromo-2,5-dimethylthiophene 1,1-dioxide ( 1 ) with L -prolinol ( 9 ), piperidine-2-methanol ( 10 ), and piperidine-2-ethanol ( 11 ), yielding the dienes (2S)-1-[(2E,4Z)-4-bromohexa-2,4-dienyl]pyrrolidine-2-methanol ( 12 ), 1-[(2E,4Z)-4-bromohexa-2,4-dienyl]piperidine-2-methanol ( 13 ), and 1-[(2E,4Z)-4-bromo-hexa-2,4-dienyl]piperidine-2-ethanol ( 14 ; Scheme2), which, after conversion into their α,β-unsaturated esters, cyclized in a TiCl₄-catalyzed intramolecular Diets-Alder reaction (Scheme3). A discussion on the mechanism of the ring opening reaction including semiempirical and ab initio calculations is also presented.     

1-Substituted 1,3-Dihydroisothianaphthen-2,2-dioxides: Preparation and Use as ortho-Quinodimethane Precursors in Intramolecular Cycloadditions. Preliminary communication

1,3-Dihydroisothianaphthen-2,2-dioxide (1) was readily converted to the 1-substituted sulfones 3 by deprotonation and subsequent electrophilic attack (Scheme 3 and Table). The appropriate 1-alkenyl- and 1-alkenoyl-sulfones 3 on heating at 213° to 240° underwent SO₂-extrusion to give, via the non-isolated (E)-quinodimethanes II (Scheme 1), polycyclic products such as 4, 6 and 7 in good yields (Schemes 4 and 5). On the other hand, thermolysis of the 1-alkenoyl-1-thioether sulfones 9 furnished mainly the isochromenes 10 (Scheme 6).     

Über die «aus dem Ring»-Claisen-Umlagerung von Naphthalinderivaten

When a mixture of (E)- and (Z)-1-propenylnaphth-2-yl-allylether ((E/Z)- 5 ) is heated to 182° only the (E)-isomer rearranges to give the ‘out-of-ring’ product (E/Z)- 16 , (Z)- 5 remains unchanged. At higher temperature (Z)- 5 yields 2-methyl-naphtho[2,1-b]furane ( 15 ) as the main product. The mixture of β-chloro-allyl derivatives (E/Z)- 6 behaves in a similar way. These findings led us to suspect that the ‘out-of-ring’ products 16 and 18 are formed by direct [1, 5s] allyl migration from the starting ethers (E)- 5 and (E)- 6 . Kinetic' measurements made on (E)- and (Z)- 5 and the independently synthesized (E)- and (Z)-1-allyl-1-propenyl-1 H-naphthalen-2-ones ((E)- and (Z)- 17 ) show however, that the ethers (E)- 5 and (E)- 6 undergo a double [3s, 3s] rearrangement (i.e. Claisen followed by Cope rearrangement) and hydrogen migration to yield the ‘out-of-ring’ products (E/Z)- 16 and (E/Z)- 18 (Scheme 9). In the (Z)-series steric factors prevent the intermediate naphthalenones (Z)- 17 and (Z)-19 from undergoing the Cope rearrangement and instead, at higher temperature, cleavage of the allyl group occurs (Scheme 11). The isopropenyl derivative 7 behaves in a similar way (Scheme 5). Rearrangement of (E/Z)-1-propenylnaphth-2-yl benzyl ether ( 8 ) requires a higher temperature (214°). The nature of the products obtained (Scheme 4) makes the occurrence of a direct sigmatropic [1,5s] shift of the benzyl group very unprobable. In the case of (E/Z)-2-propenylnaphth-1-yl allyl ether ( 10 ) both isomers rearrange to yield the ‘out-of-ring’ product 30 and the para-Claisen product 32 (Scheme 7). This experiment also provides evidence against a sigmatropic [1,5s] shift of the allyl group. The same conclusion can be drawn from the thermal behaviour of (E/Z)-2-propenylphenyl allyl ether (11) and 6-t-butyl-2-propenylphenyl allyl ether ( 12 ) where only 11 yields traces of the ‘out-of-ring’ product 35 (Scheme 8). Up to this date there is no evidence whatsoever for the existence of a sigmatropic [1,5s] migration of an allyl group from oxygen to carbon. Thermal rearrangement of (E/Z)-1-propenylnaphth-2-yl propargyl ether ( 9 ) yields only (E/Z)-1-propenyl-benz[e]indan-2-one ( 27 ) (and its secondary product 28 ). The mechanism for this reaction is given in Scheme 12. Treatment of a mixture of (E/Z)- 18 with base yields the (Z)-cyclisation product 2,4-dimethylnaphth[2,1-b]oxepine ( 43 ) (Scheme 13).     

Photochemical reactions. 152nd Communication. Photochemistry of acylsilanes; photolysis and thermolysis of cyclopropyl silyl ketones

The photolysis and thermolysis of the Cyclopropyl silyl ketones 3, 4 , and 5 are described. On n,π* excitation, the silyl ketones 3 and 4 undergo a Norrish-type-II reaction involving γ-H abstraction, cyclopropyl ring cleavage followed by retro-enolization to the acylsilanes 6 and (E/Z)- 12 , respectively. As a common product of 3 and 4 , the dihydrofuran 7 is formed via the alternative C(α)-C(β) cleavage of the cyclopropyl moiety. Compounds 6 , 7 , and (E/Z)- 12 are new types of acylsilane photoproducts. The irradiation of acylsilane 5 gave the analogous dihydrofuran 15 as the only product. On photolysis of 3 and 4 , products 8A + B and 13A + B , derived from a siloxy carbene intermediate, were found as well. On thermolysis of 3 and 4 , the acylsilanes 6 (80%), and (E)- 12 (33%) and (Z)- 12 (34%), respectively, are formed as the only products. Their formation may occur via a [1, 5] sigmatropic H-shift. The thermolysis of 5 gave the diene 16 whose formation can be explained by insertion of a siloxycarbene into the neighboring cyclopropane leading to the cyclobutene 28 as thermally unstable intermediate.