Synthese und Chiralität von (5R, 6R)-5,6-Dihydro-β, ψ-carotin-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotin-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β, ψ-carotin und (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotin

Synthesis and Chirality of (5R, 6R)-5,6-Dihydro-β, ψ-carotene-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotene-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,ψ-carotene and (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotene Wittig-condensation of optically active azafrinal ( 1 ) with the phosphoranes 3 and 6 derived from all-(E)-ψ-ionol ( 2 ) and (+)-(R)-α-ionol ( 5 ) leads to the crystalline and optically active carotenoid diols 4 and 7 , respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9 , respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].     

Synthesis of Retro-γ-Ionols and the Corresponding-Ionones1

Both the direct² and the sensitized^3,4 photolyses of (E)-β-ionol (2) have been studied in some detail. In a preliminary publication⁵ we have indicated that direct photolyses of (E)-β-ionol (2) with λ = 254 nm yields (Z)-retro-γ-ionol (3) as the primary product; upon further irradiation 3 is converted into the corresponding (E)-isomer (4) which rapidly yields the bicyclic alcohol 5. A quantitative study revealed that the photoconversion of (E)-β-ionol with λ = 254 nm to 3 is about 10 times faster than the conversion of 3 into (E)-retro-γ-ionol.⁶ This rate difference thus allows the photosynthesis of 3.     

Ionic liquid soluble photosensitizers

The preparation and investigation of triplet photosensitizers designed to be preferentially soluble in room-temperature ionic liquids are reported. Photosensitizers prepared by covalent attachment of 1-methylimidazole to aryl ketones are soluble in ionic liquids and remain in the ionic liquid layer when the solution is extracted with an organic solvent. The photosensitized isomerization of trans-β-ionol to cis-β-ionol was efficiently carried out in ionic liquid solution with the product ionol being extracted and the sensitizer/ionic liquid mixture being re-used in additional photosensitization reactions. The scope and utility of the sensitizers in sensitizing other reactions are discussed.     

Total Synthesis of (+)‐β‐Himachalene

An enantioselective synthesis of (+)‐β‐himachalene ( 2 ) was accomplished starting from (1S,2R)‐1,2‐epoxy‐p‐menth‐8‐ene ( 3 ) in 15 or 16 steps with an overall yield of ca. 6% (Schemes 3, 5, and 6). Key transformations include an Ireland–Claisen rearrangement, a Corey oxidative cyclization, and a ring expansion.     

Synthese von (±)-α-Chamigren. Vorläufige Mitteilung

Synthesis of (±)-α-Chamigrene Cis- and trans-β-ionol (cis and trans- 1 ) underwent acid catalysed dehydration to a mixture of the tetraenes 2–5 in 70–80% yield (Table 1). Irradiation of this mixtures made the 6-(Z), 8-(Z)-isomer 5 accessible (columns 3 and 4 in Table 1). Pyrolysis of the different mixtures at 170° showed, that both isomers, 3 and 5 respectively undergo electrocyclization to dehydrochamigrene ( 6 ). The latter was reduced to α-chamigrene ( 7 ) by hydrogen on Lindlar catalyst.     

Substitution and elimination reactions in aluminum oxide: 1-alpha- and 1-beta-benzoyloxy-delta-2-cholestene and 3-beta-chlor-delta-1-cholestene

The formerly discribed [1] unknown substance CHT 208, which was obtained as side product when 3β-benzoyloxy-Δ¹-cholestene ( 3 ) was treated with ‘neutral’ activated alumina in an unpolar solvent, has been recognized as consisting of ca. 67% 3β-hydroxy-Δ¹-cholestene ( 6 ) and of ca. 33% 3β-hydroxy-Δ¹-cholestene ( 4 ) (molecular compound 2:1). Analogous treatment of 3β-chloro-Δ¹-cholestene ( 5 ) with alumina yielded the same mixture of the allylic alcohols 4 and 6 as substitution products and of Δ^1,3-cholestadiene ( 2 ) as elimination product in equal amounts.     

An Unusual Rearrangement of a Lithiated N-Acyl-tetrahydroisoquinoline to an Amino-indan Skeleton and Structural Comparison of 3-Amino-2-methylindan- and -tetrahydronaphthalene-2-carboxylic Acids as Possible Building Blocks for Peptide-Turn Mimics

Lithium 1-lithio-6,7-dimethoxy-3-methyl-2-pivaloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of 5,6-dimethoxy-2-methyl-1-(pivaloylamino)indan-2-carboxylic acid ( 2 , [1,2]-sigmatropic shift with retention of configuration) by 1,2-migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives ( 6 , 7 , 10 , 15 ) to the metalating conditions. Only one other compound was found to undergo the same rearrangement ( 15 → 16 ). Possible mechanisms of the rearrangement are discussed ( B–G ). Due to the presence of a tetrasubstituted C-atom, the indan-type β-amino-acid derivative 2 has a conformationally locked structure (N? C? C? CO₂R dihedral angle 44°). For comparison, the corresponding tetralin-type β-aminoacid derivatives 19–22 were prepared, and it was shown by X-ray analysis (of the ester 21 ) that these have larger dihedral angles (ca. 60°). It is proposed that β-amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.     

Beckmann-Umlagerung und Fragmentierung,III. Teil Versuche zur 7-Zentren-Fragmentierung eines γ-Aminoketoxims: Fragmentierungsreaktionen, 20. Mitteilung

In aqueous dioxane the p-toluenesulfonate 11B of 1β-dimethylamino-5-oximino-trans-decalin (11a) undergoes almost quantitative Beckmann rearrangement to the lactam 23. Approx. 1%, only, of the product of so-called 7-centre fragmentation, i.e. trans-9-cyano-non-5-enal (14) is detectable. Furthermore, the picryl ether 11C of the oxime 11a reacts at a normal rate. The results confirm the conclusion reached earlier, namely that fragmentation cannot compete with the Beckmann rearrangement in the case of γ-amino ketoximes, in contrast to the behaviour of α-amino ketoximes.     

Rh(II)-Catalyzed Isomerizations of Cyclopropenes Evidence for Rh(II)-Complexed Vinylcarbene Intermediates

The thermocatalytic rearrangements of cyclopropenes 1-4 have been investigated in the presence of Rh(IT) perfiuorobutyrate. 1, 2, 3-Triphenylcyclopropene ( 1a ) undergoes rearrangement lo diphenylindene 5a or, with alkoxycyclopropene derivatives, to α, β-unsaturated ketone 6. Furan formation occurs with 2, 3-diphenylcyclo-propenecarboxylate 2, but the diethyl counterpart 3 rearranges to dienoate 8. 2-Alkylcyclopropenecarboxylates 4 afforded (E)-methylidenecyclopentane derivatives 9 as the only isolable product in yields of ca. 35 %. A mechanism involving regio- and stereospecific cyclopropene ring opening to a Rh-complexed vinylcarbene and insertion of the latter into the C? H bond to give 9 is proposed. An analogous mechanism should account for the rearrangement products of 1 to 3 .     

Diazoaldehyde Chemistry. Part 1. Transdiazotization of Acylacetaldehydes in Neutral-to-Acidic Medium. A Direct Approach to the Synthesis of α-Diazo-β-oxoaldehydes

First ever non-deformylating transdiazotization of acylacetaldehydes was achieved: the reactions of 2-azido-l-ethylpyridinium tetrafluoroborate ( 4 ) with acylacetaldehydes 3 proceeded partially without deformylation to yield 16 new α-diazo-β-oxoaldehydes 1 along with diazomethyl ketones 2 , especially in the presence of NaOAc (Scheme 1, Tables 1 and 2). The product distribution was substituent-dependent and could be correlated quantitatively. This new diazotization reaction appears as an alternative, direct, and more general method for the synthesis of these diazooxoaldehydes. α-Oxocycloalkanecarbaldehydes 5 gave only traces (if any) of α-diazocycloalkanones 7 , and rearrangement products 6 were isolated (Scheme 2). Mechanisms of the reactions are discussed (Schemes 4 and 5).     

Inhaltsstoffe des Osmanthus-Absolues. 4. Mitteilung: Megastigma-5, 7 (E), 9-trien-4-on und Megastigma-5, 8 (E)-dien-4-on

Constituents of Osmanthus Absolute, 4th Communication. Megastigma-5, 7 (E), 9-triene-4-one and Megastigma-5, 8 (E)-diene-4-one In continuation of our communications on constituents of Osmanthus absolute, we now report on the occurrence of the two title compounds 1 and 2a in this natural substrate (0.01-0.02% each). Their structures were confirmed by synthesis starting from β-ionone via the common intermediate 4-oxo-β-ionol ( 9 ). Some further minor components bearing corresponding structural features are tabulated in view of possible biogenetic pathways leading to 1 or 2a , respectively. In order to clarify the olfactory behaviour, we also synthesized some analogous derivatives in the irone series, these substances being not yet found in nature.     

Base Catalysed Reaction of 1bT,2β-Epoxy-γ-Tetrahydrosantonin

In an earlier communication¹ we have already reported the acid catalysed rearrangement of 1β,2β-epoxy-γ-tetrahydrosantonin (II). This epoxyketone was obtained from the corresponding unsaturated ketone (I)² by base catalysed epoxidation with H₂O₂ in 66% yield. Formation of compound II in less than quantitative yield prompted us to examine the aqueous leftover of the reaction. This has led to the isolation and characterisation of two compounds with novel structures, III, resulting from I through epoxidation, Baeyer-Villiger oxidation followed by further transformations in basic media and V, a product resulting from Favorskii-type rearrangement of the epoxyketone (II). The spectral data which formed the     

Dediazoniation of Arenediazonium Ions. Part XIX. Effect of thiocyanate ion in the reactions of 2,4,6-trimethylbenzenediazonium tetrafluoroborate in 2,2,2-trifluoroethanol

The dediazoniation of 2,4,6-trimethylbenzenediazonium tetrafluoroborate ( 1 ) in 2,2,2-trifluoroethanol (TFE) was studied in the presence of potassium thiocyanate. The effect of added salt on the dediazoniation rate, the N_α-N_β rearrangement (Eqn. 2), the exchange of the ¹⁵N-labelled diazo group with molecular nitrogen (Eqn. 3), and the reaction products was determined. With 0.3_M KSCN a dediazoniation-rate increase of 16.5% was achieved, and the amounts of rearranged and exchanged product were reduced to 88% and 70%, respectively, of the values found in pure TFE. The dediazoniation products formed are ArF ( 3 ), ArOCH₂CF₃ ( 4 ), ArSCN ( 5 ), ArNCS ( 6 ) and traces of 5, 7-dimethylindazole ( 7 ). All the data are in agreement with, and support the previously proposed mechanism (Equ. 1) of heterolytic dediazoniation of arenediazonium salts.     

Preparation of N-Fmoc-Protected β2- and β3-Amino Acids and their use as building blocks for the solid-phase synthesis of β-peptides

N-Fmoc-Protected (Fmoc = (9H-fluoren-9-ylmethoxy)carbonyl) β-amino acids are required for an efficient synthesis of β-oligopeptides on solid support. Enantiomerically pure Fmoc-β³-amino acids β³: side chain and NH₂ at C(3)(= C(β)) were prepared from Fmoc-protected (S)- and (R)-α-amino acids with aliphatic, aromatic, and functionalized side chains, using the standard or an optimized Arndt-Eistert reaction sequence. Fmoc-β²- Amino acids (β² side chain at C(2), NH₂ at C(3)(= C(β))) configuration bearing the side chain of Ala, Val, Leu, and Phe were synthesized via the Evans' chiral auxiliary methodology. The target β³-heptapeptides 5–8 , a β³- pentadecapeptide 9 and a β²-heptapeptide 10 were synthesized on a manual solid-phase synthesis apparatus using conventional solid-phase peptide synthesis procedures (Scheme 3). In the case of β³-peptides, two methods were used to anchor the first β-amino acid: esterification of the ortho-chlorotrityl chloride resin with the first Fmoc-β-amino acid 2 (Method I, Scheme 2) or acylation of the 4-(benzyloxy)benzyl alcohol resin (Wang resin) with the ketene intermediates from the Wolff rearrangement of amino-acid-derived diazo ketone 1 (Method II, Scheme 2). The former technique provided better results, as exemplified by the synthesis of the heptapeptides 5 and 6 (Table 2). The intermediate from the Wolff rearrangement of diazo ketones 1 was also used for sequential peptide-bond formation on solid support (synthesis of the tetrapeptides 11 and 12 ). The CD spectra of the β²- and β³-peptides 5 , 9 , and 10 show the typical pattern previously assigned to an (M) 3₁ helical secondary structure (Fig.). The most intense CD absorption was observed with the pentadecapeptide 9 (strong broad negative Cotton effect at ca. 213 nm); compared to the analogous heptapeptide 5 , this corresponds to a 2.5 fold increase in the molar ellipticity per residue!     

On the photochemical conversion of an alpha, beta-unsaturated gamma, delta-epoxy ketone: 3-oxo-6-alpha, 7-alpha-oxide-17-beta-acetoxy-Delta-androstane

The α,β-unsaturated γ,δ-epoxyketone 7 is isomerized almost exclusively to the δ-diketone 9 both upon irradiation in the n → π* absorption band with light of wavelengths above 310 nm (in anhydrous dioxane or benzene solutions) and upon triplet sensitization using acetophenone in benzene. The reaction may be formulated by the cleavage of the C_γ? O oxide bond and the shift of the δ-hydrogen to the γ-position, and thus bears a formal “double bond homology” to the photochemical α,β-epoxyketone rearrangement. Excitation in the π → π* absorption band of 7 with light of wavelength 253,7 nm (in anhydrous dioxane solution) leads to the formation of product 10 as well as to the triplet rearrangement to 9 . With this result a novel partial synthesis of O-acetyl-B-nortestosterone has been accomplished, which has the advantages of fewer steps and higher product yield ( 7 → 10 : ～30% yield) than previously published syntheses. On the basis of the presently available experiments, the mechanism of the transformation 7 → 10 , which constitutes one of the still few examples of enone photoreactions induced selectively from the π,π* excited singlet, remains unknown.     

Synthesis of Tricyclic Ketones with Sesquiterpene Skeletons by Acid-Catalyzed Rearrangement of β-Monocyclofarnesol

Starting from dihydro-β-ionone ( 6 ) a mixture of three tricyclic ketones with sesquiterpene skeletons 14 , 15 , and 16 was prepared by Wittig-Horner reaction with triethyl phosphonoacetate, Red-Al^® reduction, acid-catalyzed rearrangement of the resulting β-monocyclofarnesol ( 7 ), alkaline hydrolysis of the formates 8 – 10 , and subsequent molybdenium-catalyzed oxidation. The mechanistic background of the acid-catalyzed rearrangement of β-monocyclofarnesol ( 7 ) is discussed in detail. The resulting tricyclic ketones 14 – 16 exhibit intense woody odor notes with peppery vetiver or camphoraceous cedarwood aspects.     

An Unusual Domino Retro‐Ene–Conia Reaction: Regio‐ and Stereoselective One‐Carbon Ring Expansion of Fenchol Derivatives

The 2-exo-substituted fenchol derivatives 1 – 7 , easily prepared from (−)-fenchone in good-to-excellent yields, were pyrolyzed by dynamic gas-phase thermo-isomerization (DGPTI). At temperatures of ca. 620°, the substrates with a hydroxyallyl ( 1 – 4 ) or a hydroxypropargyl moiety ( 6 ) underwent an initial retro-ene reaction under cleavage of the C(2) C(3) bond to form enol-ene intermediates with no loss of optical activity. These intermediates then experience either tautomerization to the corresponding α,β-unsaturated ketones or subsequent Conia rearrangement under one-carbon ring expansion of the fenchone system to a bicyclo[3.2.1]octane framework. In the case of the isopropenyl substrate 3 , the sterically crowded Conia product underwent a new type of ‘deethanation’ reaction by stepwise loss of two Me radicals, giving rise to the thermodynamically favored enone 21 . A similar relaxation behavior was observed in the case of the ethynyl substrate 6 , which showed a remarkable 1,3-Me shift after the Conia reaction, leading to the α,β-unsaturated cyclic ketone 25 . The homolytic cleavage of the weakest single bond in 1 – 3 turned out to be a competing reaction pathway. Intramolecular H-abstraction within the generated diradical intermediates produced the monocyclic ketones 8, 16 , and 19 , besides the products obtained by tautomerization and Conia reaction. In contrast, a Ph substituent at C(2) in 7 allowed only the passage through a diradical species to provide phenone 26 , which was converted by regioselective Baeyer–Villiger oxidation to the optically active cyclopentanol 29 . Both reaction channels, the domino retro-ene–Conia rearrangement and the diradical-promoted H-transfer, have been shown to proceed highly stereoselectively. The absolute configuration of the newly formed stereogenic centers in all compounds was assigned by ¹H-NOE experiments. The reaction mechanism of the novel domino retro-ene–Conia reaction was established by both a series of ²H- and ¹³C-labeling experiments, as well as by a detailed computational analysis.     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。     

Photooxygenolytic Degradation of the Vitamin-B12 Derivative Heptamethyl Coα,Coβ-Dicyanocobyrinate. Efficient Preparation of Bicyclic Fragments

The methylene-blue sensitized photooxygenation of heptamethyl Coα,Coβ-dicyanocobyrinate ( 1 , cobester) at ca. ?45° and in (D₃)acetonitrile solution proceeds readily to the stage of selective double cleavage of the corrin macrocycle. It furnishes the bisected heptamethyl Coα,Coβ-dicyano-5,6:14,15-tetraoxo-5,6:14,15-disecocobyrinate ( 3 ) in 91% yield after warming the photooxygenation mixture to room temperature. Complex 3 is also obtained by photooxygenation of the secocorrinoid oxygenation products of 1 , namely of heptamethyl Coα,Coβ-dicyano-5,6-dioxo-5,6-secocobyrinate ( 2a ) and of its isomer heptamethyl Coα,Coβ-dicyano-14,15-dioxo-14,15-secocobyrinate ( 2b ). When the raw photooxygenation product of 1 is kept at low temperature, 3 is not formed in a significant amount; spectral analysis reveals 4 as intermediate that is transformed into 3 quantitatively upon warm-up and storage at r.t. Compound 4 is assigned the structure of heptamethyl Coα,Coβ-dicyano-5,6-epidioxy-5,6-dihydro-14,15-dioxo-14,15-secocobyrinate, based on NMR-spectral data and since 4 is also formed cleanly in the corresponding low-temperature photooxygenation of 2b . Catalytic reduction of the Co(III) complex 3 (H₂, Pt/C) in the presence of EDTA produces a colourless oil, from which the bicyclic fragments 5 (corresponding to rings A and D of 1 ) and 6 (corresponding to rings B and C of 1 ) are obtained in 99 and 91% yield, respectively, after chromatographic separation.     

Synthese von (R)-β, β-Carotin-2-ol und (2R, 2′R)-β, β-Carotin-2,2′-diol

Synthesis of (R)-β, β-Caroten-2-ol and (2R, 2′R)-β, β-Carotene-2,2′-diol Starting from geraniol, the two carotenoids (R)-β, β-caroten-2-ol ( 1 ) and (2R, 2′R)-β, β-carotene-2,2′-diol ( 3 ) were synthesized. The optically active cyclic building block was obtained by an acid-catalysed cyclisation of the epoxide (R)- 4 . The enantiomeric excess of the product was > 95 %.