Photoreaktionen von 1-Alkylbenztriazolen

The irradiation of benzotriazoles (cf. Scheme 2) with light of 225–325 nm in protic and in aromatic solvents was investigated. In aqueous 0.1N H₂SO₄ benzotriazole ( 5 ) and 1-methyl-benzotriazole ( 6 ) yielded 2-amino- and 2-methylaminophenol ( 25 and 26 ), respectively (Scheme 3). In 2-propanol 6 , 5-chloro- and 6-chloro-1-methyl-benzotriazole ( 14 and 15 ) were reduced to N-methylaniline, 4-chloro- and 3-chloro-N-methyl-aniline ( 27 , 28 and 29 ), respectively (Scheme 4). When the benzotriazoles were irradiated in aromatic solvents only C, C coupling products were observed (cf. Scheme 6 and Tables 1–4). It is of importance that 5-chloro-1-methyl-benztriazole ( 14 ) when decomposed photolytically in benzene solution yielded only 4-chloro-2-phenyl-N-methyl-aniline ( 49 ) and its 6-chloro isomer only 5-chloro-2-phenyl-N-methyl-aniline ( 50 ), i.e. the intervention of benzo-1H-azirine intermediates (e.g. 53 , Scheme 8) can be excluded. The substitution patterns which are observed when 6 is irradiated in toluene, anisole, fluoro-, chloro-, bromobenzene and benzonitrile (cf. Table 4) can best be explained by assuming that 6 , after loss of nitrogen, forms a diradical intermediate in the singlet state with highly zwitterionic character. 1-(1′-Alkenyl)-benzotriazoles (cf. Table 7) form on irradiation in cyclohexane solution indoles by intramolecular ring closure of the diradical intermediate and proton shift. After irradiation of 1-decyl-benzotriazole ( 8 ) in a glassy matrix at 77K a 7-line ESR. spectrum characteristic of a triplet radical is observed. This is in agreement with the fact that the lowest lying state of intermediates of type 2 (Scheme 1) should be a triplet state (cf. [21] [26]).     

Additionen von 2,2-Dimethyl-3-dimethylamino-2H-azirin an 2-Formyl-cycloalkanone und Sulfinsäuren

2,2-Dimethyl-3-dimethylamino-2H-azirine ( 1 ) reacts with the formyl-cycloalkanones 4 – 8 in boiling benzene to give the 1:1 adducts 13 – 17 in 60–99% yield (Table). These adducts are N′-[(2-oxo-cycloalkylidene)-methyl] derivatives of 2-amino-N, N-dimethylisobutyramide. The reaction mechanism (Scheme 6) is analogous to the mechanism of the reaction of 1 with carboxylic acids and cyclic enolisable 1,3-diketones [1]. Sulfinic acids and 1 undergo a similar reaction at ?15° to yield 2-sulfinamido-N, N-dimethylisobutyramides (Schemes 4 and 7), while sulfonic acids and the azirine 1 lead to a dimeric salt of type 20 , which with sodium hydroxide gives the dihydropyrazine 21 (Scheme 5).     

Aromatische sigmatropische Wasserstoffverschiebungen in 2-Vinyl- und 2-Allylphenolen

Aromatic Sigmatropic Hydrogen-Shifts in 2-Vinyl- and 2-Allyl-phenols It is shown by deuterium labeling experiments that 2-vinylphenols, on heating at 142,5°, undergo aromatic [1,5]-H-shifts whereby o-quinone methides are formed as intermediates (Scheme 7). Thus, heating of 2-isopropenylphenol ( 6 ) in a D₂O/dioxane mixture leads to a rapid deuterium incorporation into the methylidene group of the isopropenyl moiety (Table 1) whereas its methyl group shows only a slow uptake of deuterium. The latter exchange process can be attributed to intermolecular reactions (Scheme 8). The quinone methide intermediates (e.g. 26 , Scheme 8) can be regarded as vinyl homologues of alkyl ketones. Therefore, 26 can exchange hydrogen in both methyl groups by an acid- and base-catalysed mechanism. Indeed, when 6 is heated in D₂O/pyridine or D₂O/CH₃COOD/dioxane, an almost statistical incorporation of deuterium into the methylidene and the methyl group of the isopropenyl moiety is observed (Table 3). As a consequence of thermally induced [1,5]-H-shifts, 2-(1′-propenyl)-phenols undergo rapid (E,Z) isomerization with first order kinetics on heating above 140° in decane solution. Activation parameters are given in Table 4. The observed primary +++++ H/D isotope effect of 3.3 in the (E,Z) isomerization of phenol 8 is in +++ment with intramolecular H/D-shifts in the rate determing step (Scheme 9 +++ Table 5). As expected aromatic sigmatropic [1,5]-H-shifts in 2-(1′-propenyl)-+++ are much faster than aromatic homosigmatropic [1,5]-H-shifts in 2-(2′-+++++)phenols (Scheme 1 and Table 6). The structurally comparable phenols +++ (Z)- 10 and (E)/(Z)- 14 (Scheme 3) show k([1,5])/k(homo-[1,5]) ≈ 2300 at ++++

1 A more detailed discussion in English is given in [1].

.     

Intramolekulare Inversionssubstitution am Dreiring von 77exo-Brombicyclo[4.1.0]heptan-3endo-ol unter Bildung eines Tetrahydrofuranringes

Intramolecular Substitution under Inversion at the Threemembered Ring of 7exo-Bromobicyclo[4.1.0]heptan-3endo-ol yielding a Tetrahydrofuran Ring The reaction 1a → 2a involving substitution at a cyclopropane carbon atom can be observed only with the bromophilic alkyllithium reagents but not with the bases lithium diisopropyl amide (LDA) (Table 1) or potassium t-butoxide (KTB). The mechanism must be an insertion as outlined in Scheme 1. - The monobromides 1b , 1c and 1d are prepared stereoselectively from the acetal 3a . Again, cyclization of 1b takes only place with LDA in the presence of alkyllithium (Table 2, entries 1--4) suggesting an insertion mechanism (route (a) or (b) in Scheme 2). In contrast, KTB effects the substitution in high yield with no loss (from 1c ) or incorporation of deuterium at the cyclopropane substitution center (Table 2, entries 5--7); the possibility is discussed that this process is an S_N2-type reaction.     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

Rhodium(II)‐Catalyzed Inter‐ and Intramolecular Enantioselective Cyclopropanations with Alkyl‐Diazo(triorganylsilyl)acetates

The intermolecular cyclopropanation of styrene with ethyl diazo(triethylsilyl)acetate ( 1a ) proceeds at room temperature in the presence of chiral Rh^II carboxylate catalysts derived from imide‐protected amino acids and affords mixtures of trans‐ and cis‐cyclopropane derivatives 2a in up to 72% yield but with modest enantioselectivities (<54%) (Scheme 1 and Table 1). Protiodesilylation of a diastereoisomer mixture 2a with Bu₄NF is accompanied by epimerization at C(1) (→ 3 ). The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetate ( 8a ), in turn, affords optically active 3‐oxabicyclo[3.1.0]hexan‐2‐one ( 9a ) with yields of up to 85% and 56% ee (Scheme 3 and Table 2). Similarly, the (2Z)‐pent‐2‐enyl derivative 8d reacts to 9d in up to 77% yield and 38% ee (Scheme 3 and Table 3). In contrast, the diazo decomposition of (2E)‐3‐phenylprop‐2‐enyl and 2‐methylprop‐2‐en‐1‐yl diazo(triethyl‐silyl)acetates ( 8b and 8c , resp.) is unsatisfactory and gives very poor yields of substituted 3‐oxabicyclo[3.1.0]hexan‐2‐ones 9b and 9c , respectively (Table 3).     

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].     

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).     

Zur Photochemie von 1H- und 2H-Indazolen in saurer Lösung

On the Photochemistry of 1H- and 2H-Indazoles in Acidic Solution It is shown that 1H- and 2H-indazoles (cf. Scheme 2) on protonation (0, 1N H₂SO₄ in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N (1), N (2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf. Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf. Schemes 4–10). Photolysis of indazole ( 4 ) and 3-methyl-indazole ( 5 ) in 0,75N H₂SO₄ in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf. Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf. Schemes 11 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf. Schemes 11 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf. Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf. Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cf. Scheme 20) thus, destabilizing the singlet state relative to the triplet state.     

Alkylation Reactions at the Benzo Moiety of 2,4‐Dimethoxy‐3‐(phenylsulfonyl)benzo[a]heptalenes – Model Compounds of Colchicinoids

Alkylation reactions of 3‐(X‐sulfonyl)benzo[a]heptalene‐2,4‐diols (X=Ph, morpholin‐4‐yl) and their dimethyl ethers were studied. The diols form with K₂CO₃/MeI in aqueous media the 1‐methylated benzoheptalenes, but in yields not surpassing 20% (Table 1). On the other hand, 2,4‐dimethoxybenzo[a]heptalenes can easily be lithiated at C(3) with BuLi and then treated with alkyl iodides to give the 3‐alkylated forms in good yield (Table 2). Surprising is the reaction with two equiv. or more of t‐BuLi since the alkylation at C(4) is accompanied by the reductive elimination of the X‐sulfonyl group at C(3) (Table 3). Most exciting is also the course of 2,4‐dimethoxy‐3‐(phenylsulfonyl)benzo[a]heptalenes in the presence of an excess of MeLi. After the expected exchange of MeO against Me at C(4) (Scheme 6), rearrangement takes place under formation of 4‐benzyl‐2‐methoxybenzo[a]heptalenes and concomitant loss of the sulfonyl group at C(3) (Table 4). In the case of X=morpholin‐4‐yl, rearrangement cannot occur. However, the intermediate benzyl anions of Type E (Scheme 8) react easily with O₂ of the air to build up corresponding benzo[a]heptalene‐4‐methanols (Table 6).     

Acid-Catalyzed [3,3]-Sigmatropic Rearrangements of N-Propargylanilines

The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)-, N-(1′-methylprop-2′-ynyl)-, and N-(1′-arylprop-2′-ynyl)-2,6-, 2,4,6-, 2,3,5,6-, and 2,3,4,5,6-substituted anilines in mixtures of 1N aqueous H₂SO₄ and ROH such as EtOH, PrOH, BuOH etc., or in CDCl₃ or CCl₄ in the presence of 4 to 9 mol-equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12-25 and Tables 6 and 7). The rearrangement of N-(3′-X-1′,1′-dimethyl-prop-2′-ynyl)-2,6- and 2,4,6-trimethylanilines (X = Cl, Br, I) in CDCl₃/TFA occurs already at 20° with τ_1/2 of ca. 1 to 5 h to yield the corresponding 6-(1-X-3′-methylbuta-1,2′-dienyl)-2,6-dimethyl- or 2,4,6-trimethylcyclohexa-2,4-dien-1-iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]-sigmatropic rearrangement takes place to yield 2,6-dimethyl-4-(3′-X-1′,1′-dimethylprop-2′-ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N-(3′-chloro-1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ( 45 ., cf. Table 7). The acid-catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H₂SO₄/ROH at 85-95°, in addition, leads to the formation of 7-chlorotricyclo[3.2.1.0^2,7]oct-3-en-8-ones as the result of an intramolecular Diels-Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium-ion intermediate, a [1,2]-sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]-sigmatropic rearrangement to yield the corresponding 3-allenyl-substituted anilines (cf. Schemes 12,14–18, and 20 as well as Tables 6 and 7). The rearrangement of (?)?(S)-N-(1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 38 ; cf. Table 7) in a mixture of 1N H₂SO₄/PrOH at 86° leads to the formation of (?)-(R)-3-(3′-phenylpropa-1′,2′-dienyl)-2,6-dimethylaniline ((?)- 91 ), (+)-(E)- and (?)-(Z)-6-benzylidene-1,5-dimethyltricyclo[3.2.1.0^2′7]oct-3-en-8-one ((+)-(E)- and (?)-(Z)- 92 , respectively), and (?)-(S)-2,6-dimethyl-4-( 1′-phenylprop-2′-ynyl)aniline((?)- 93 ). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)-(E)- and (?)-(Z)- 92 showed the same optical purity as (minus;)- 38 , as expected for intramolecular concerted processes. The CD of (+)-(E)- and (?)-(Z)- 92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid-catalyzed rearrangement of (?)-(S)-N-(3′-chloro-1′phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 45 ; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N–C(1′) bond in (?)- 45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid-catalyzed rearrangement of (?)-(S)-2,6-dimethyl-N-[1′-(p-tolyl)prop-2′-ynyl]aniline ((?)- 42 ; cf. Scheme 25). N-[1′-(p-anisyl)prop-2-ynyl]-2,4,6-trimethylaniline( 43 ; cf. Scheme 25) underwent no acid-catalyzed [3,3]-sigmatropic rearrangement at all. The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)aniline ( 25 ; cf. Scheme 10) in 1N H₂SO₄/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid-catalyzed rearrangement of the corresponding 3′-Cl derivative at 130° in aqueous H₂SO₄ in ethylene glycol led to the formation of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-on ( 54 ; cf. Scheme 10), the hydrolysis product of the expected 4-chloro-1,2-dihydro-2,2-dimethylquinoline ( 56 ). Similarly, the acid-catalyzed rearrangement of N-(3′-bromo-1′-methylprop-2′-ynyl)-2,6-diisopropylaniline ( 37 ; cf. Scheme 21) yielded, by loss of one i-Pr group, 1,2,3,4-tetrahydro-8-isopropyl-2-methylquinolin-4-one ( 59 ).     

Asymmetric induction bny enantiotopically differentiating retro-claisen reaction of P{rochiral bicyclic β-diketones

The possibility of preparing cycloalkanones with an asymmetric β-C-atom by enantiotopically differentiating retro-Claisen reactions of bicyclic diketones a (Scheme l) is tested with the decalin-1,8-diones 1 and 7 , as well as with the bicyclo[3.3.0]octane-2,8-diones 10 and 11 . Treatment of the reactive dione 1 with chiral tetra-alkyl titanate catalysts results in a low optical induction (13%, Scheme 2). Cleavage with the Nasalts of a-amino-alcohols and hydrolysis of the resulting amides or esters gives much better optical yields, reaching 86% ee with dione 1 and (?)-ephedrine (Scheme 3). Almost as efficient is N-methylephedrine with 75% optical induction (Scheme 5). Lower enantiotopical differentiation is, however, observed with (?)-ephedrine and diones 7 (44% ee), 10 (8% ee), and 11 (48% ee) (Schemes 3 and 4, Table l), or with dione 1 and _L-prolinol (37% ee) or (?)-2-amino-1-butanol (11% ee) (Scheme 5, Table 2). The moderate chemical yields of these transformations (500–70%) can be ascribed to side-reactions of the ketones under the strongly basic conditions.     

Nucleophilic Addition to C,C Double Bonds. Proximity and homoconjugative effects. Preliminary communication

Proximity effects alone as well as in combination with electronic effects are responsible for the observed phenomenon of base-catalyzed ether formation initiated by nucleophilic attack on a C, C double bond of the tricyclic olefin alcohols 1–10 (Scheme 1, Table 1). With compounds 1–4 , bearing a keto group, formation of the ethers 11–14 proceeds through a corresponding homoenolate b (Scheme 2) as an intermediate. In one case such a species could be trapped as the methyl ether 21 (Scheme 3). Special attention is given to the stereochemical course of the homoketonization. Ring opening in 21 under acidic conditions occurs regioselectively, however non-stereoselectively (Scheme 3). Full regio- and stereoselectivity (retention) is observed under basic conditions starting from the unsaturated keto alcohols 1 and 2 (Scheme 4) as well as from the keto ethers 11 and 12 (Scheme 5, Table 2).     

Minimally Competent Lewis Acid Catalysts: Indium(III) and Bismuth(III) Salts Produce Rhamnosides (=6‐Deoxymannosides) in High Yield and Purity

Glycosylation of decan‐1‐ol ( 2 ), (±)‐decan‐2‐ol ( 3 ), and (±)‐methyl 3‐hydroxydecanoate ( 4 ) with L ‐rhamnose peracetate 5 to produce rhamnosides (=6‐deoxymannosides) 6, 7 , and 8 in the presence of Lewis acids BF₃?Et₂O, Sc(OTf)₃, InBr₃, and Bi(OTf)₃ was studied (Table 1). While the strong Lewis acids BF₃?Et₂O and Sc(OTf)₃ were effective as glycosylation promoters, they had to be used in excess; however, glycosylation required careful control of reaction times and temperatures, and these Lewis acids produced impurities in addition to the desired glycosides. Enantiomerically pure rhamnosides (R)‐ 1 and (S)‐ 1 (Fig.) were obtained from L ‐rhamnose peracetate 5 and (±)‐benzyl 3‐hydroxydecanoate ( 9 ) via the diastereoisomeric rhamnosides 10 (Table 2; Scheme 3). The much weaker Lewis acids InBr₃ and Bi(OTfl)₃ produced purer products in high yield under a wider range of conditions (higher temperatures), and were effective glycosylation promoters even when used catalytically (<10% catalyst; Table 2). We refer to these Lewis acids as ‘minimally competent Lewis acids’ (cf. Scheme 4).     

Heterospirocyclic N‐(2H‐Azirin‐3‐yl)‐L‐prolinates: New Dipeptide Synthons

The synthesis of methyl N‐(1‐aza‐6‐oxaspiro[2.5]oct‐1‐en‐2‐yl)‐L ‐prolinate ( 1e ) has been performed by consecutive treatment of methyl N‐[(tetrahydro‐2H‐pyran‐4‐yl)thiocarbonyl]‐L ‐prolinate ( 5 ) with COCl₂, 1,4‐diazabicyclo[2.2.2]octane (DABCO), and NaN₃ (Scheme 1). As the first example of a novel class of dipeptide synthons, 1e has been shown to undergo the expected reactions with carboxylic acids and thioacids (Scheme 2). The successful preparation of the nonapeptide 16 , which is an analogue of the C‐terminal nonapeptide of the antibiotic Trichovirin I 1B, proved that 1e can be used in peptide synthesis as a dipeptide building block (Scheme 3). The structure of 7 has been established by X‐ray crystal‐structure analysis (Figs. 1 and 2).     

Zur Photochemie von 2, 1-Benzisoxazolen (Anthranilen) und thermischen und photochemischen Umsetzungen von 2-Azido-acylbenzolen in stark saurer Lösung

On the Photochemistry of 2, 1-Benzisoxazoles (Anthraniles) and on the Thermal and Photochemical Decomposition of 2-Azido-acylbenzenes in Strongly Acidic Solution Anthranils 6 (Scheme 3), when irradiated with a mercury high-pressure lamp, in 96% sulfuric acid yielded, after work-up, 2-amino-5-hydroxy-acylbenzenes 8 and as side products 2-amino-3-hydroxy-acylbenzenes 9 (cf. Schemes 5–7 and Table 1). When C(5) of the anthranils 6 carries a methyl group a more complex reaction mixture is found after irradiation in 96% sulfuric acid (cf. Schemes 8 and 9): 3, 5-dimethyl-anthranil ( 6d ) yielded (after irradiation and acetylation) 2-acetyl- amino-5-methyl-acetophenone ( 15 ), 2-acetylamino-5-acetoxymethyl-acetophenone ( 18d ) and 2-acetylamino-5-acetoxy-6-methyl-acetophenone ( 12c ). The latter product was also formed after irradiation of 3, 4-dimethylanthranil ( 6c ) in 96% sulfuric acid. 3, 5, 7-Trimethyl-anthranil ( 6f ) formed under the same conditions 2-acetylamino-3, 5-dimethyl-acetophenone ( 15f ) and 2-acetylamino-5-acetoxymethyl-3-methyl-acetophenone ( 18f ). Since qualitatively the same product patterns were observed when the corresponding 2-azido-acetophenones 7 were decomposed in 96% sulfuric acid it is concluded that anthranilium ions (cf. 6b -H⊕, Scheme 11) on irradiation are transformed by cleavage of the N, O-bond into 2-acyl-phenylnitrenium ions (cf. 25b -H⊕) in the singlet ground state. The nitrenium ions are trapped directly by nucleophiles ( HSO ?₄ in 96% sulfuric acid), thus, yielding the hydroxy-acetophenones 8 and 9 (Scheme 11). If C(5) is blocked by a methyl group a [1, 2]-rearrangement of the methyl group may occur (cf. Scheme 13) or loss of sulfuric acid can lead to quinomethane iminium ions (cf. 32-H⊕ , Scheme 13) which will react with HSO ?₄ ions to yield, after hydrolysis and acetylation, the 5-acetoxymethyl substituted acetophenones 18d and 18f . It is assumed that the reduction products (2-acetylamino-acetophenones 15 ) are formed from the corresponding nitrenium ions in the triplet ground state.     

Synthese des Sesquiterpen-Ketones Shyobunon und seiner Diastereomeren

Synthesis of the Sesquiterpene Ketone Shyobunon and of its Diastereoisomers Shyobunon ( 12 ) and 6-epishyobunon ( 13 ) as well as their epimers 10 and 11 were synthetized in five steps from geranyl- ( 1 ) and nerylsenecionate ( 2 ), respectively. Ester enolate rearrangement [5] of 1 and 2 furnished the key intermediates 3 and 4 in high yield and in about 80% stereoselectivity [6] (Scheme 1). Conversion of the acid mixture 3 / 4 to the cyclohexanone derivatives 7 and 8 succeeded in 35–40% yield by means of cyclization of their acidchlorides with tin tetrachloride to the mixture of 5 and 6 , followed by HCl elimination with diazabicyclononene (DBN) (Scheme 2). Selective reduction of 7 to 10 and 11 , and 8 to 12 and 13 with triphenyltinhydride completed the synthesis. The relative configuration of 10 and 11 as well as of 12 and 13 were deduced from the ¹³C-NMR. spectra (Scheme 4, Table 2). The structure of ‘epishyobunone’ is revised: it has the structure 13 , and not 11 as described earlier [1]. This is discussed in connection with the rearrangement of acoragermacrone ( 16 ) [18] to shyobunone ( 12 ) and 6-epishyobunone ( 13 ) (Scheme 5).     

3-(Dimethylamino)-2,2-dimethyl-2H-azirin als α-Aminoisobuttersäure(Aib)-Äquivalent: Cyclische Depsipeptide durch direkte Amid-Cyclisierung

3-(Dimethylamino)-2,2-dimethyl-2H,-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and α-hydroxycarboxylic acids react to give diamides of type 8 (Scheme 3). Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H₂O leads to the corresponding carboxylic acids 13 (Scheme 4). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5). Starting with diamides 8 , the formation of morpholin-2,5- diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11 (Scheme 3). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units (Scheme 4). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18 , and 21 , respectively.     

Acid-Catalysed Dehydration of Tricyclic Unsaturated Alcohols

The tricyclic alcohols 3–7 , derived from the corresponding ketones 1 and 2 (Scheme 1), by action of acids underwent dehydration with skeletal rearrangements. Dehydration of 3 and 4 with POCl₃/pyridine (procedure A) afforded the polycyclic hydrocarbons 9, 10 , and 12, 13 , respectively. With TsOH (procedure B), on the other hand, 3 and 4 gave homo-triquinacenes 10 and 14 respectively, as well as the polycyclic ethers 11 and 15 (Scheme 2). Hydrocarbon 9 (or 12 ) was converted into 10 FSO₃H to the tertiary alcohol 16 (Scheme 4). Plausible mechanisms for these transformations are summarized in Scheme 8. Dehydration of the secondary alcohols 5 and 7 was effected by procedure A. While treatment of alcohol 5 with POCl₃/pyridine yielded two isomeric hydrocarbons 17 and 18 , similar dehydration of its epimeric alcohol 7 afforded hydrocarbon 21 as the sole product. The tertiary alcohol 6 was dehydrated by both procedures to yield two isomeric hydrocarbons 19 and 20 (Scheme 5). Hydrocarbon 20 was converted into 19 by procedure B (mechanisms, Scheme 10). Reaction of ketone 2 with CF₃COOH gave the addition product 22 converted into vinylsulfonyl fluorides 24 and 25 by treatment with FSO₃H (Scheme 6). Homo-triquinacenes 10 and 14 reacted smoothly with 4-phenyl-1,2,4-triazoline-3,5-dione to give the ‘ene’-reaction products 26 and 27 , respectively.