Photochemische Reaktionen. 104. Mitteilung [1]. Zur Photospaltung der C,C-Oxiranbindung konjugierter γ, δ-Epoxy-enone: Photolyse von 4-Methyliden-5,6-epoxy-5,6-dihydro-β-jonon

The photoinduced cleavage of the C,C-oxirane bond of γ, δ-epoxy-enones: UV.-irradiation of 4-methylidene-5,6-epoxy-5,6-dihydro-β-ionone On ¹n, π*-excitation (λ ≥ 347 nm, pentane) 5 gives the isomeric bicyclic ether 10 in 75% yield (s. Scheme 2). In methanol the photoconversion of 5 to 10 is strongly reduced (12%) in favour of the formation of the methanol adduct 11 (43%). On photolysis in aqueous acetonitrile 5 is converted to the bicyclic ether 10 (9%), the dihydrofurane 12 (18%) as well as to the triketones 13A and 13B (7%), and 14 (23%). On ¹π, π*-excitation (λ = 254 nm) in pentane no 10 is formed, but 5 isomerizes to the tricyclic cyclopropyl compound 16 (59%), the allenic product 17 (10%), and the cyclopropene compound 18 (12%; s. Scheme 3). Photolysis in methanol furnishes 11 (63%), and 18 (4%), but no tricyclic cyclopropyl compound 16 . In a secondary photoreaction (λ = 254 nm) the dihydrofurane 12 is isomerized to the bicyclic cyclopropyl compound 20 . Evidence is given that the products 11 and 13 are formed by solvent addition to an intermediate ketonium ylide b (s. Scheme 12). The presence of b is further proven by the formation of 12 , a product of an electrocyclization of b . On photofragmentation of b carbenoids d and e are presumably formed (s. Scheme 14). 1,2-Hydrogen shift in d yields the allene derivative 17 , and cyclization of d gives the cyclopropene compound 18 . On the other hand, e cyclizes to the non isolated cyclopropene compound 69 which is transformed to 16 by an intramolecular [4 + 2]-cycloaddition. The present investigation shows that the photochemistry of 5 is determined by photoinduced C,C-bond cleavage of the oxirane ring. This is in sharp contrast to the photochemistry of conjugated γ, δ-epoxy-enones without the additional double bond in ε, ζ-position, where selective photocleavage of the C(λ), O-bond is observed.     

Photochemische Reaktionen. 83. Mitteilung. Verbindungen der 3,4-Dihydrojonon-Reihe als Modelle zur Photochemie γ, δ- bzw. δ, ϵ-ungesättigter Ketone und Aldehyde

Compounds of the 3,4-dihydro-ionone series as models for the photochemistry of γ, δ- and δ,?- unsaturated ketones and aldehydes . The photochemistry of γ, δ- and δ,?-unsaturated carbonyl compounds of the dihydro-ionone series has been studied, with special attention to the investigation of oxetane formation versus hydrogen abstraction. UV.-irradiation of the dihydro-β-ionone compounds with structure A ( 1 , 7 , 14 , 18 , 24 , 29 ) led to isomeric ethers with structures B ( 2 , 8 , 15 , 19 , 25 , 30 ), C ( 3 , 9 , 16 , 20 , 26 , 31 ) and D ( 4 , 21 , 27 ), isomeric bicyclic alcohols with structure E ( 5 , 10 , 17 , 22 , 28 ), and photoreduction products with structure F ( 6 , 11 , 12 , 13 ). Photolysis of dihydro-γ-ionone ( 32 ) gave a complex mixture containing fragmentation product 35 , hydrocarbon 36 , β-ambrinol ( 34 ), oxetane 33 , as well as dihydro-β-ionone ( 1 ) and three of its photoproducts ( 2 , 3 , 5 ). The dihydro-α-ionone compounds 37 and 40 gave mixtures of fragmentation products and the oxetanes 38 and 41 . Irradiation of the side-chain homologues 42 and 45 yielded 43 , which photo-cyclizes to 44 . In contrast, 3 , 4 -dihydro-3′,4′-dehydro-β-ionone ( 46 ) gave merely the isomeric open-chain triene-ketone 47 . The structures assigned to the ethers 2 , 3 , 33 , 38 and to the alcohols 5 , 10 , 13 could be confirmed by chemical reactions and mutual interconversions. The structure of the ether 21 had to be established by X-ray analysis, details of which are described. A novel intramolecular hydrogen transfer is involved in formation of ethers B . The photocyclization A → D probably proceeds by addition of the carbonyl-C atom to the double bond ( A → h ), followed by methyl (1 → 2)-shift ( h → i ). Process A → h may also be involved in formation of compounds of type C and E .     

Die sterischen Bedingungen der Fragmentierungsreaktion I. Teil. Stereoisomere 3-Chlortropane. Fragmentierungsreaktionen, 14. Mitteilung

The steric requirements for the synchronous fragmentation of γ-aminohalides as previously postulated have been confirmed by a study of the solvolysis of stereoisomeric 3β- and 3β-chloro-tropanes and -nortropanes. 3β-chloro-tropanes ( 7 a ) and 3β-chloro-nortropane ( 7 b ), which fulfil the stereoelectronic requirements, undergo quantitative fragmentation in 80 vol.% ethanol. They react 1.35 × 10⁴ and 1.35 × 10³ times, respectively, as fast as the ‘homomorphous’ exo-3-chloro-bicyclo[3.2.1]octane ( 12 a ). Fragmentation therefore takes place by the synchronous mechanism.     

Photochemische Reaktionen. 103. Mitteilung [1]. Zur Photochemie konjugierter Epoxy-en-carbonylverbindungen der Jonon-Reihe: UV.-Bestrahlung α,β-ungesättigter ε-Oxo-γ, δ-epoxy-carbonylverbindungen und Untersuchung des Mechanismus der Epoxy-enon/Furan-Isomerisierung

The Photochemistry of Conjugated γ,δ-Epoxy-ene-carbonyl Compounds of the Ionone Series: UV.-Irradiation of α,β-Unsaturated ε-Oxo-γ,δ-epoxy Compounds and Investigation of the Mechanism of the Isomerization of Epoxy-enones to Furanes On ¹n, π*-excitation (λ ≥ 347 nm; pentane) of the enonechromophore of 3 , three different reactions are induced: (E/Z)-isomerization to give 13 (7%), isomerization by cleavage of the C(γ)–C(δ) bond to yield the bicyclic ether 14 (36%) and isomerization by cleavage of the C(γ)? O bond to give the cyclopentanones 15 (13%) and 16 (11%; s. Scheme 2). On ¹π, π*-excitation (λ = 254 nm; acetonitrile) 13 (14%), 15 (6%), and 16 (6%) are formed, but no 14 is detected. In contrast, isomerization by cleavage of the C(δ)? O bond to give the cyclopentanone 17 (23%) is observed. The reaction 3 → 17 appears to be the consequence of an energy transfer from the excited enone chromophore to the cyclohexanone chromophore, which then undergoes β-cleavage. Irradiation of 4 with light of λ = 254 nm (pentane) yields the analogous products 20 (18%), 21 (9%), 22 (7%), and 24 (7%; s. Scheme 2). Selective ¹n, π*-excitation (λ ≥ 280 nm) of the cyclohexanone chromophore of 4 induces isomerization by cleavage of the C(δ)? O bond to give the cyclopentanones 23 (9%) and 24 (44%). Triplet-sensitization of 4 by excited acetophenone induces (E/Z)-isomerization to provide 20 (12%) and isomerization by cleavage of the C(δ)? O bond to yield 21 (26%) and 22 (20%), but no isomerization via cleavage of the C(δ)? O bond. It has been shown, that the presence of the ε;-keto group facilitates C(γ)? C(δ) bond cleavage to give a bicyclic ether 14 , but hinders the epoxy-en-carbonyl compounds 3 and 4 from undergoing cycloeliminations. The activation parameters of the valence isomerization 13 → 18 , a thermal process, have been determined in polar and non-polar solvents by analysing the ¹H-NMR. signal intensities. The rearrangement proceeds faster in polar solvents, where the entropy of activation is about ?20 e.u. Opening of the epoxide ring and formation fo the furan ring are probably concerted.     

Gerüstumlagerung eines α,β -ungesättigten γ,δ-Epoxiketons bei der Birch-Reduktion: Strukturaufklärung mittels 13C-INADEQUATE-NMR-Spektroskopie

Skeleton Rearrangement of an α-β-Unsaturated γ,δ-Epoxyketone during Birch Reduction: Structure Elucidation by Means of ¹³C-INADEQUATE-NMR Spectroscopy When the γ-epoxide 2 of β-ionone is treated under standard Birch-reduction conditions, unexpectedly a 70% combined yield of regioisomeric octalones 4 and 5 is isolated. These products unquestionably result form cleavage of the central epoxide C?C bond. The structure of compounds 4 and 5 could be determined by means of ¹³C-INADEQUATE-NMR spectroscopy.     

Photochemische Reaktionen. 68. Mitteilung. Die Photoisomerisierung von α,β-ungesättigten γ,δ-Epoxyketonen: 9α, 10α- und 9β, 10β-Oxido-3-oxo-17β-acetoxy-Δ4-östren

Irradiation in the n→π* absorption band of the α,β-unsaturated γ,δ-epoxyketone 5 in ethanol at ?65° exclusively afforded the rearranged ene-dione 13 , whereas at + 24° under otherwise unchanged reaction conditions or upon triplet sensitization with Michler's ketone and with acetophenone at + 24° essentially identical mixtures of 13 (major product), 14 , and 15 were obtained. Selective π→π* excitation of 5 at ?78° and + 24° led to similar product patterns. The 9β,10β-epimeric epoxyketone 7 selectively isomerized to 14 and 15 at + 24° and n → π* or π → π* excitation. Neither the epoxyketones 5 and 7 nor the photoproducts 13–15 were photochemically interconverted. In separate photolyses each of the latter gave the double bond isomers 16 , 18 , and 19 , respectively. Cleavage of 13 to the dienone aldehyde 17 competed with the double bond shift ( → 16 ) when photolyzed in alcoholic solvents instead of benzene. The selective transformations 5 → 13 (at ?65° and n → π* excitation) and 7 → 14 + 15 are attributed to stereoelectronic factors facilitating the skeletal rearrangements of the diradicals 53 and 55 , the likely primary photoproducts resulting from epoxide cleavage in the triplet-excited compounds 5 and 7 , via the transition states 54 , 56 , and 57 . The loss of selectivity in product formation from 5 at higher temperature and n → π* excitation or triplet sensitization is explicable in terms of radical dissociation into 58 and 59 increasingly participating at the secondary thermal transformations of 53 . The similar effect of π → π* excitation even at ?78° indicates that some of the π,π* singlet energy may become available as thermal activation energy. It is further suggested that the considerably lesser ring strain in 14 and 15 , as compared with 13 , is responsible that selectivity in product formation from 7 is maintained also at +24° and at π → π* excitation.     

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a – 11f , mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f ₂ was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH₂CH₂O‐D ‐Val(F₆)‐MeLeu‐Ala‐O^tBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f ₂ was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f ₁ with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L ‐valine]]cyclosporins 14a and 14b , respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.     

P(CH(3)NCH(2)CH(2))(3)N as a dehydrobromination reagent: synthesis of vitamin A derivatives revisited.

Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.     

Reaktionen mit phosphororganischen Verbindungen. XLII. Nucleophile Substitutionen an Hydroxysteroiden mit Hilfe von Triphenylphosphan/Azodicarbonsäureester

Nucleophilic Substitution Reactions of Hydroxysteroids using Triphenylphosphane/diethylazodicarboxylate Nucleophilic substitution reactions by means of the title reagent on various more or less hindered steroid alcohols with suitable nucleophils in benzene is described. It was not possible to run this substitution process in the hitherto used solvent THF. Cholestan-3α-ol ( 1 ) was transformed to the 3β-substituted products 3β-benzoyloxy-cholestane ( 1a ) and 3β-azido-cholestane ( 1b ). Testosterone ( 2 ) affords with the corresponding nucleophils after short heating in benzene the inverted 17α-substituted products 3a, 3b and 3c . Analogously the 17α-azido-derivative 5a arises from 17β-hydroxy-androst-3-on ( 4 ). In the presence of a ketogroup in the substrate a competitive reaction can occur as it is shown in the case of cholestan-3-on ( 6 ): the products are the en-hydrazo-dicarboxylate-steroids 7a and 7b . The sterically very hindered 11α-position in 11α-hydroxy-4-pregnen-3,20-dion ( 8 ) can be transformed also to the 11β-azide 9a . The substitution of a 6 β-hydroxy group in androstane-3β, 6β, 17β-triol-3,17-diacetate ( 10 ) to the 6α-azide 11a affords the elimination product 12 as main component. Trans-diaxial vicinal diols such as cholestane-2β,3α-diol ( 13 ) give a mixture of the α- and β-oxiranes 14a and 14b .     

Zur Reaktionsweise von Enaminen mit Cyclopropenonen IV. Einsatz von Ketenacetalen

A new interpretation – based on a reevaluation of the spectroscopic properties of products 16 to 27 – is proposed for the reaction of diphenyl-cyclopropen-one 14 and -thione 15 with ketene-A, N-diacetals 8 to 13 (A ? R₂N, RO and RS) originally reported by Sauer & Krapf. It is concluded that the previous structural assignments (see the a-structures), made on the assumption of a prevailing “C,C-insertion” reaction, must be rcplaced as follows: (1) All the “secondary adducts” are, in fact, derivatives (amides and lactams) of 2,3-diphenyl-penta-2, 4-dienoic acid and thioacid (structures 16b to 24b ); (2) the “isomerization products”, differ from the latter only in the configuration of the α,β-double bond (structures 25b and 26b ); (3) the common “hydrolysisproduct” is α,β-diphenyl-γ-methyl-γ-hydroxy-Δ^α-butenolide ( 27b ), The above cyclopropenone-ketcneacetal reactions represent, therefore, cases of “C, N-insertion”. This is rationalized with a reaction scheme, in which the “acylide” structure of the “primary adducts” plays a role.     

Cyclization of ylidenemalononitriles. X. Synthesis of benzazapropellane derivatives from α-Cyano-β-chloroalkylcinnamonitriles

The reaction of nucleophilic and non-nucleophilic bases wtih 2-carbamoyl-3-(γ-chloropropyl)-1-indenone ( 5 ) have been investigated. Condensation of γ-chlorobutyrophenone with malono-nitrile afforded α-cyano-β-(3-ehloropropyl)cinnamonitrile which was cyclized in concentrated sulfurie acid to produce 5 . Two other products obtained from the cyclization reaction were 2-carbamoyl-3-(γ-ehloropropylidene)-1-indanone ( 4 ) and α-carbamoyl-β-(3-chloropropyl)cinnam-amide. Treatment of a solution of 4 in ethyl acetate with piperidine resulted in cyclization of the γ-chloropropyl side chain to give 2-carbamoyl-3-cycIopropyl-1-indanone. The same compound was obtained in improved yield by the treatment of 4 or 5 with sodium hydroxide solution. The reaction of dirnethylamine with 5 in benzene gave initial Michael addition of the amine followed by internal alkylation of the carbanion so formed to yield 3a-dimethylamino-2,3,3a,8-tetrahydro-8-oxoeyclopent[a]indene-8a(lH)earboxamide ( 7a ). Similarly addition of ammonia, pyrrolidine, piperidine, benzenethiol, p-toluenethiol, 2-naphthalenethiol and nitromethane to the indenone I gave respective analogs of type 7 . Treatment of 5 with sodium cyanide in aqueous t-butyl alcohol resulted in a similar Michael addition followed by internal alkylation. In addition, cyclization between the nitrile and the carbamoyl functions occurred in the same step to give 2-oxo-4-imino-7,8-benzo-3-aza[3.3.3]-propellan-6-one ( 13a ). Hydrolysis of the iminopyrrolido ring in 13a to the corresponding suecin-irnide gave 2,4-dioxo-7,8-benzo-3-aza[3.3.3]propellan-6-one ( 13b ). Reactión of 13b with methyl iodide, allyl bromide, benzyl bromide, and diethyluminoethyl chloride afforded the corresponding N-alkylated products. A similar sequence starling with δ-ehlorovalerophenone led to 5,6-fused ring systems, including a [4.3.3]propellane. 2,9-Dioxo-4-methyl-7,8-benzo-3-aza[4.3.3]propell-4-ene was obtained by the reaction of 5 with acetone in dilute alkali.     

Photochemische Reaktionen. 106. Mitteilung. Zur Photochemie tetraalkylsubstituierter γ-Keto-olefine

The Photochemistry of Tetraalkyl Substituted γ-Keto-olefines The photochemistry of 7,8-dihydro-β-ionone ( 1 ) in solution is shown to depend on temperature, polarity and viscosity of the solvent. UV. irradiation (λ ≥ 245 nm) in pentane at +25° converts 1 to the isomeric ethers 3 (16%), 5A (48%) and 5B (22%), whereas at ?65° 7,8-dihydro-γ-ionone ( 26 ) is obtained in 12% yield together with 13% of 3 , 12% of 5A and 9% of 5B . The ¹n,π*-excitation of 1 in acetonitrile gives similar results. In the more viscous 1,2,3-triacetoxypropane the photoisomerization 1 → 26 takes place even at + 60° (10% yield, cf. 40% at ?15°). In alcoholic solvents, however, no formation of 26 is detected, but the hitherto unknown [2+2]-photocycloaddition 1 → 11 can be observed (4% at ?7°, 15% at ?65S° in 2-propanol). An intermediate e may be involved (Scheme 14). In addition to the photoreactions 1 → 3, 5A, 5B and 11 the isomerization of 1 to the novel spirocyclic ketone 28 takes place in alcoholic solvents only. Photoisomerization 1 → 3 is presumably a photo-ene process involving a stereoselective intramolecular H-transfer. This type of photoisomerization is restricted to cyclic γ-keto-olefines. The tetraalkylated acyclic γ-keto-olefines 14 and 15 photoisomerize exclusively by [2+2]-cycloaddition, independent of the solvent. On ¹n,π*-excitation the δ,?-unsaturated bicyclic ketone 44 undergoes Norrish-Type-II photofragmentation to the diene 45 or isomerizes to the γ, ?-unsaturated ketone 17 . Competition between these two reactions is strongly temperature dependent: photolysis in pentane at ?72° yields quantitatively 45 , whereas at + 35° only 30% of 45 and 68% of 17 are obtained. UV. irradiation of the novel spirocyclic ketone 28 gives as primary photoproduct the isomeric aldehyde 29 , and in a secondary photoreaction the isomeric oxetanes 30A and 30B . Experiments with deuteriated substrates show that the isomerization of type 28 → 29 is stereocontrolled.     

Photochemische Reaktionen. 90. Mitteilung. Die UV.-Bestrahlung von (E)-5-Isopropyl-6-methyl-5,6-epoxy-hept-3-en-2-on

Photolysis of (E)-5-Isopropyl-6-methyl-5,6-epoxy-hept-3-en-2-on. This paper continues the series of investigations of the photochemistry of α, β-unsaturated γ, δ-epoxy-ketones, by examinating the photochemical behaviour of the aliphatic vinylogous epoxy-ketone 1 , the chromophore of which is structurally similar to that of γ, δ-epoxy-(E),β-ionone ( 44 ). On π, π*-excitation (λ = 254 nm) 1 isomerizes mainly to the enol-ether 2 and gives as minor products the isomeric dihydrofurane 3 , the 1,5-diketones 4 and 5 and the 1,3-diketone 6 . To a smaller extent, 1 also undergoes photofragmentation to the furane 7 , the allenyl-ketone 8 and the cyclopropenyl-ketone 9 . On n,π*-excitation (λ ≥ = 347 nm) 1 yields the photoisomers 3 , 4 , 5 and in traces the hydroxyallenyl-ketone 14 , but no fragmentation products. It is shown that on irradiation at λ ≥ = 254 nm the 1,5-diketone 4 isomerizes to 5 , 6 and 15 and photodecarbonylates to the β, γ-unsaturated ketone 16 . The isomers 3 , 4 and 5 , obtained both from n, π*- and π,π*-excitation, represent products of cleavage of the C(γ)? O-bond in 1 . The enolether 2 , on the other hand, formed only by π,π*-excitation, results from cleavage of the C(γ)? C(δ)-bond. Finally, the fragmentation products 7 , 8 and 9 , which could be detected only on π,π*-excitation, may arise from a common intermediate g ? h .     

Quinazolines et benzodiazépines-1,4. LX Imidazo[5,1-c]benzodiazépines-1,4

Upon treatment with oxalyl chloride followed by reaction with the appropriate nucleophile, the 3-carbamoyl-benzodiazepines 6 , 7 and 8 were converted stereospecifically to the tricyclic compounds 12, 13, 14, 16 and 19 . Epimerization of 19 in presence of p-toluenesulfonic acid led to 21 . The stereochemistry of these tricyclic compounds and of some of their N(2)-alkyl derivatives ( 22-31 ) has been established by NMR. spectroscopy. Under proper reaction conditions, attack by bases on the tricyclic esters 13 and 26 was shown to cause an inversion of the chiral center C(11a) and to yield stereospecifically rearranged products, e.g. 23 from 26 and 33 from 13 .     

Photochemical reactions. 141st communication. Photochemistry of α,β-unsaturated δ,ϵ-epoxyketones of the ionone series

On n,π*- as well as on π,π*-excitation, the 4,5-epoxy-α-ionones (E)- 1 , (E)- 2 , and (E)- 3 undergo (E)/(Z)-isomerization and subsequent γ-H-abstraction leading to the corresponding 4-hydroxy-β-ionones (E/Z)- 9 , (E/Z)- 13 , and (E/Z)- 17 as primary photoproducts. On photolysis of (E)- 3 , as an additional primary photoproduct, the β,γ-unsaturated σ,?-epoxy ketone 18 was obtained. The other isolated compounds, namely the 2H-pyrans 10A + B and 14A + B as well as the retro γ-ionones 11 and 15A + B , represent known types of products, which are derived from the 4-hydroxy-β-ionones (E/Z)- 9 and (E/Z)- 13 , respectively.     

Sigmatropische Umlagerungen von Aryl-propargyläthern; Synthese von 1, 5-Dimethyl-6-methylen-tricyclo[3, 2, 1, 02,7]-oct-3-en-8-on-Derivaten. Vorläufige Mitteilung

2, 6-Dimethylphenyl propargyl ether ( 10 ) and its derivatives 12–15 rearrange thermally to 1, 5-dimethyl-6-methylene-tricyclo [3.2.1.0^2,7]oct-3-en-8-one ( 9 ) and related compounds 16–19 . The ethers undergo first an aromatic [3, 3]-sigmatropic rearrangement to ortho-allenyldienones 11 , which then undergo ring closure to the tricyclic products by an electrocyclic reaction. Only in the case of the γ-methylpropargyl ether 13 , the ortho-dienone 11 is further rearranged in low yield to the para-butynylphenol 20 , but the tricyclic ketone 17 is again the main product. New data show that the known thermal cyclisation of aryl propargyl ethers to chromenes (e. g. 4 → 8 ) involves a preliminary [3, 3]-sigmatropic rearrangement.     

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.     

Reactions of Sulfanyl Chlorides with Thiocamphor and Thiofenchone: Wagner?Meerwein Rearrangement of an Intermediate Thiocarbonylium Ion

The reaction of sulfanyl and disulfanyl chlorides with thiocamphor ( 6 ) in the presence of Et₃N leads to unsymmetrical di‐ and trisulfanes, respectively (Schemes 2 and 4). A reaction mechanism via a thiocarbonylium ion, which is immediately deprotonated, is proposed. The formation of a minor product 10 in the absence of a base, resulting from a Wagner? Meerwein rearrangement, is an additional evidence for the intermediacy of a thiocarbonylium ion (Scheme 3). On the other hand, the non‐enolizable thiofenchone ( 13 ) reacts with sulfanyl chlorides in CH₂Cl₂/Et₃N to give exclusively products with a rearranged bicyclic skeleton (Scheme 5). A Wagner? Meerwein rearrangement of the intermediate thiocarbonylium ion is the key step. The structures of the products 10 and 14 , which have rearranged bicyclic systems, have been established by X‐ray crystallography.     

Asymmetrische Michael-Additionen. Stereoselektive Alkylierung chiraler,nicht racemischer Enolate durch Nitroolefine. Herstellung enantiomerenreiner γ-Aminobuttersäure- und Bernsteinsäure-Derivate

Asymmetric Michael-Additions. Stereoselective Alkylation of Chiral, Non-racemic Enolates by Nitroolefins. Preparation of Enantiomerically Pure γ-Aminobutyric and Succinic Acid Derivatives Chiral, non-racemic lithium enolates ( E , F , G ) of 1,3-dioxolan-4-ones, methyl 1,3-oxazolidin-4-carboxylates, methyl 1,3-oxazolin-4-carboxylates, 1,3-oxazolidin-5-ones, and 1,3-imidazolidin-4-ones derived from (S)-lactic acid ( 2a ), (S)-mandelic acid ( 2b ), and (S)-malic acid ( 2c ), or from (S)-alanine ( 10 ), (S)-proline ( 11 ), (S)-serine ( 12 ), and (S)-threonine ( 13 ), are added to nitroolefins. Michael adducts ( 3 – 9 , 14 – 18 ) are formed (40–80%) with selectivities generally above 90% ds of one of the four possible stereoisomers. Conversions of these nitroalkylated products furnish the α-branched α-hydroxysuccinic acids 28 and 29 , the α-hydroxy-γ-amino acid 25 , the α,γ-di-amino acid 32 , the substituted γ-lactames 19 – 22 , and the pyrrolidine 23 . The relative and absolute configuration of the products from dioxolanones and nitropropene are derived by chemical correlation and NOE measurements indicating that the steric course of reaction is to be specified as 1k, ul-1,3. The mechanism is discussed.     

Glykoside von Marsdenia erecta R. Br. 2. Mitteilung: Versuche zur Strukturbestimmung der Genine. Glykoside und Aglykone, 330. Mitteilung

Structures for the genins of the ester glycosides of Marsdenia erecta are suggested. They are based on the behaviour in alkaline hydrolysis of these ester glycosides, their NMR. and mass spectra and ORD. data. All genins are derived from three acyl-free pregnane derivatives, i.e. drevogenin-P ( 1 ), 17 β-marsdenin ( 3 ) and marsectohexol ( 7 ). The structure of 1 is known, 3 and 7 are new compounds, i.e. 3 = 3β,8β,11α,12β,14β-pentahydroxy-Δ⁵-pregnen-20-one and 7 = 3β,8β,11α,12β,14β,20ξ-hexahydroxy-Δ⁵-pregnene. Formulae 13–17 were attributed to the acyl-genins A-1, A-2, A-3, A-4 and A-5, but only two of them were pure compounds, i.e. acyl-genin A-3 = 11,12-di-O-tiglyl-17β-marsdenin ( 15 ) and acyl-genin A-5 = 11,12-di-O-acetyl-marsectohexoi ( 17 ). Acyl-genin A-1 is a mixture of the two esters 13a + 13b derived from drevogenin-P, and similarly acyl-genin A-2 is a mixture of the esters 14a + 14b derived from 17β-marsdenin. The poorly characterised acyl-genin A-4 is most probably a mixture of the esters 16a + 16b , also derived from 17β-marsdenin.