Synthesen und Ringerweiterungsreaktionen von 2-(4-Hydroxyalkyl)-2-nitrocycloalkanonen

Syntheses and Ring-Enlargement Reactions of 2-(4-Hydroxyalkyl)-2-nitrocycloalkanones Syntheses of the title compounds were achieved by [Pd{P(C₆H₅)₃}₄]-catalyzed reaction of 2-nitrocycloalkanones 3 with vinyloxirane followed by catalytic hydrogenation. By another route, the known methyl 4-(1-nitro-2-oxocycloalkyl)butanoates 6 were reduced to the corresponding aldehydes 7 which by NaBH₄ reduction or methylation with (CH₃)₂Ti(i-Pr)₂ were transformed to the alcohols 5 and 8 , respectively (Saheme 1). Treatment of 5 and/or 8 with KH/THF under reflux gave, via a 7-membered intermediate, the nitrolactones 12 and oxolactones 13 (Scheme 3). Compared with similar reactions running via 5- or 6-membered intermediates (see 1 and 2 ), the yields are distinctly lower. The natural occurring 12-tridecanolid ( 14 ) was synthesized.     

Oxidation of N-acyl-2-(cycloalk-1-enyl)anilines with ozone and hydrogen peroxide

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH₄ gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me₂S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H₂O₂ in HCOOH affords -(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H₂O₂ in the presence of Na₂WO₄ and H₃PO₄ gives 3,1-benzooxazine in high yield.     

Stereoselektive Synthese von Pyrrolizidin-Alkaloiden aus Nitroalkanonen

Stereoselective Synthesis von Pyrrolizidin Alkaloids from Nitroalkanones Reduction of 5-nitropentadecane-2,8-dione ( 11 ), synthesized by a Michael reaction from nitromethane, methyl vinyl ketone, and dec-1-en-3-one, gave, depending on the conditions, two epimeric 3-heptyl-2,3,5,6,7,7a-hexahydro-5-methyl-1H-pyrrolizines as the main products: Catalytic hydrogenation (Pd/C) afforded the expected 7aα-hydro epimer 1b with cis-orieted H-atoms at C(3), C(5), and C(7a). NaBH₃CN/NH₄OAc reduction of the nitrodione 11 yielded all four diastereoisomers with the 7aβ-hydro epimer 1a as the predominant component; 1a is a pheromone of the cryptic thief ant Solenopsis sp. The N-atom of the pyrrolizidine ring stems from NH₄OAc exclusively as shown by reduction of 11 with NaBH₃CN/(¹⁵N)H₄OAc.     

Beitrag zum Reaktionsmechanismus der Synthese von Seychellen [1]

New Mechanistical Details Concerning the Synthesis of Seychellen [1] In the last step of our synthesis of Seychellen ( 2 ) [1], the solvolysis of 1 , only one side-product was formed, namely 3 (Scheme 1). Now the structure of 3 has been elucidated, mainly by spectroscopic studies of its derivatives 7 and 9 (Scheme 2). In order to differentiate between two different solvolytic pathways from 1 to 3 (see Scheme 1 and 3) d₃- 1 was prepared. Solvolysis of d₃- 1 proved the mechanism shown in Scheme 1. Solvolysis of 1 and of 2-epi- 1 , respectively, furnished the same product distribution, which makes a common intermediate a very probable. In both cases 10 is an intermediate, which is slowly converted into 2 and 3 . 2-epi- 1 was prepared from 1 (Scheme 5). Kinetic measurements with 1 , d₃- 1 and 2-epi- 1 are also in agreement with the mechanism drawn in Scheme 4: k₁(72°) = (5,2±0,5) · 10^?5 sec^?1, k₁(H)/k₁(D)(72°) = 1,4±0,15; k₂(H)/k₄(H) = 0,66 and k₂(H)/k₂(D) = 2,2 if k₄(H) ≈ k₄(D) is assumed.     

Preparation of Chiral Hydroxy Carbonyl Compounds and Diols by Ozonolysis of Olefinic Isoborneol and Fenchol Derivatives: Characterization of Stable Ozonides by 1H-, 13C-, and 17O-NMR and Electrospray Ionization Mass Spectrometry

The allylic and homoallylic alcohols 1 – 8 , prepared from (+)-camphor and (−)-fenchone, were ozonized in Et₂O at −78° and treated with Et₃N or LiAlH₄ to give the chiral hydroxy carbonyl compounds 9 – 16 and the diols 17 – 24 , respectively (Scheme 1). In the case of the diols 19 and 24 , the formation of new chiral centers proceeded with high diastereoselectivity. These diols were prepared highly diastereoselectively also by LiAlH₄ reduction of the hydroxy carbonyl compounds 11 and 16a , respectively (Scheme 2). The absolute configuration of the new chiral centers in 19 and 24 was determined by X-ray and NMR methods. The ozonization of compounds 2 , 3 , 7 , and 8 provided the relatively stable hydroxy-substituted 1,2,4-trioxolane derivatives (ozonides) 37 – 40 (Scheme 5) which were characterized by ¹H- and ¹³C-NMR spectra, ESI-MS, and natural-abundance ¹⁷O-NMR spectra.     

Synthesis of homochiral spiro [4.4]nonane-l,6-diols

Homochiral cis, cis-; cis,trans and trans,trans-spiro[4,4]-nonane-1,6-diols were prepared via diastereoselective reduction of enantiomerically pure spiro[4.4]nonane-l,6-dione (1) with the corresponding reducing agents: lithium n-butyldiisobutylaluminium hydride for cis,cis-diol (2) with 88% yield; BH₃·THF for cis, trans-diol (8) with 91% yield; LiAlH₄ for trans,trans-diol (4) with 15% yield.     

SYNTHESIS OF 4,6-DINITROINDOLE FROM 2,4,6-TRINITROTOLUENE

1-R-4,6-Dinitroindoles 4–6 (R = H, Me, Ts) could be obtained from 2-picrylethanol 1 (readily available from TNT) via selective reduction of ortho-nitro group by N₂H₄/FeCl₃ and subsequent treatment with TsCl, to yield a key intermediate 3. This intermediate was converted to the above mentioned indoles.     

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]).     

Allgemeine Basenkatalyse der Azokupplung von o-Diazophenolen. 19. Mitteilung zur Kenntnis der Azokupplungsreaktion

1. The kinetics and the mechanism of the diazo coupling reaction of 2-diazophenol-4-sulphonic acid with 1-naphthol-2-sulphonic acid have been investigated at 0° and ionic strength I=0.45. 2. The pK_a-value of the hydroxyl group in 2-diazophenol-4-sulphonic acid has been determined: pK_a=- 0.04 ± 0.10. It is the diazonium-phenolate anion which actually enters into the diazo coupling reaction. 3. The reaction is subject to general base catalysis. It is shown that no intermediate is enriched during the reaction at pH 11.3–11.6 which proceeds by a two-step mechanism with a steady state intermediate.     

Darstellung und Charakterisierung von cis- und trans-Bis(benzonitril)dichloroplatin(II) Röntgenstrukturanalysen der cis- und trans-Spezies

Synthesis and Characterization of cis- and trans-Bis(benzonitrile)dichloroplatinum(II). X-Ray Structure Analysis of Both the cis- and trans-Species The compounds cis- and trans-(C₆H₅CN)₂PtCl₂ were synthesized and characterized by means of IR and Raman spectroscopy and by X-Ray structure analysis. The trans-species crystallizes triclinic, C—1 , the cis-compound monoclinic, C—P2₁/c.     

Eine neue Synthese von (±)-Dihydrorecifeiolid

A New Synthesis of (±)-Dihydrorecifeiolide Ethyl 1-(2′-formylethyl)-2-oxocyclooctane-1-carboxylate ( 2 ) prepared by Michael reaction of ethyl 2-oxocyclooctane-1-carboxylate ( 1 ) was regioselectively methylated at the aldehyde group with (CH₃)₂Ti[OCH(CH₃)₂]₂ to give 3 (Scheme 1). The alcohol 3 was treated with Bu₄NF to give the deethoxycarbonylated product 4 which by distillation gave the bicyclic enol ether 5 . Oxidation (m-chloroperbenzoic acid) of 5 and reduction of the resulting oxolacton 6 yielded the title compound (±)-dihydrorecifeiolide ( 7 ) in an overall yield of nearly 50 %. Methylation of the aldehyde 2 with MeLi gave the ring-enlarged lacton 9 in poor yield (13 %). The deethoxycarbonylation reaction 3 → 4 was studied in more detail (Scheme 3).     

An improved synthesis of fused 1,2,3-benzothiadiphospholes and a proposed reaction pathway

A fresh look has been taken at the reaction of PCl₃ with thioanisole 1b and AlCl₃ that gives, after treatment with water, the title compounds cis- 2b in 38% yield together with small amounts of the isomeric cis- 3b (2%). The course of this reaction has been studied by ³¹P-NMR spectroscopy. A multistep pathway, governed by the formation of several AlCl₃ complexes with sulfur and phosphorus containing intermediates, has been proposed. The crucial step of this reaction is very reasonably an intramolecular electrocyclic ring closure of a diphosphane intermediate. From this plausible mechanism, an improved procedure that gives only the cis- 2b isomer in 42% yield has been realized. In addition, an alternative synthesis using p-thiocresol that gives compounds cis- 2b and cis- 3b in a ratio of about 2:1 has been effected. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8: 551–556, 1997     

Synthesis of 2-oxohexahydrothieno[3,4-d]imidazole derivatives

Conclusions We synthesized the cis-3- and 4-methyl-2-oxo-6-(-carboxybutyl) hexahydro [3,4-d]-imidazoles by the reduction of the 3- and 4-methyl-2-oxo-2,3-dihydro-6-(carboxybutyl)-1H-thieno [3,4-d] imidazoles with HSiEt₃ in CF₃COOH and subsequent alkaline hydrolysis of the intermediate methyl ethers.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1634–1636, July, 1980.The authors express their gratitude to Prof. A. Mark (France) for supplying the sample of 2-oxo-4-methyl-6-(6-carboxybutyl)hexahydrothieno[3,4-d]imidazole.     

Ringerweiterung von sechs- zu neungliedrigen Heterocyclen: Umsetzung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-on-1,1-dioxiden

Ring Enlargement of Six- to Nine-Membered Heterocycles: Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-Dioxides Reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and N-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-dioxides ( 4 ) in CHCl₃ yields 3-(dimethylamino)-4,5,6,7-tetrahydro-1,2,5,7-benzothiatriazonin-6-one 1,1-dioxides 5 , a novel nine-membered heterocyclic system, by ring enlargement (Schemes 2 and 4). In refluxing MeOH, the heterocycle 5a rearranges to give the N-[1-methyl-1-(1,1-dioxo-4H-1,2,4-benzothiadiazin-3-yl)ethyl]-N′, N′-dimethylurea 10 . The three isomeric 2-(methylamino)benzenesufonamides 8,9 , and 11 (Scheme 3) are obtained by naBH₄ reduction of 5a and 10 , respectively. Mechanisms for the thermal isomerization 5a → 10 and the NaBH₄ reduction of 5a are proposed in Schemes 5 and 6.     

Stereoselektive Synthesen von substituierten Tricarbonyl[tris(methylen)methan]eisen(0)-Komplexen

Stereoselective Syntheses of Substituted Tricarbonyl[tris(methylen)methan]iron(0) Complexes The complexes 3 , 9 , 10 , 22 , and 23 with one, two, and three Me substituents at the tris(methylen)methane moiety have been synthesized from the (acyloxy-1,3-diene)(tricarbonyl)iron(0) complexes 1 , 4 , 5 , 20 , and 21 , respectively, by ionic hydrogenation with BF₃ and Et₃SiH at ?78° in CH₂C1₂. These reductions are completely stereoselective, and their course can be predicted by assuming a dominant stereoelectronic control of the reaction. Formation of the carbocationic intermediates 11 from 4 and 12 from 5 , e.g., takes place only if the dissociating O? C bond is antiperiplanar to the donor C(β)? Fe bond. Fast H-transfer then converts the intermediate 11 to 9 and 12 to 10 . The configurations of 17 and 20 can be deduced from the structure of 22 and those of 18 and 21 from that of 23 . An X-ray structure determination of (1R,4S)camphanoate (?)- 13 derived from alcohol (?)- 7 confirms the configuration of 5 deduced above, The structures of the complexes 9 and 10 , 22 and 23 were determined by their unique NMR spectra. The diastereoisomeric complexes 6 and 7 have been synthesized from aldehyde 8 with MeMgI, the diastereoisomers 17 and 18 analogously from 16 or from methyl ketone 19 by reduction with LiAlH₄. Optically active starting materials (+)- 1 , (?)- 13 , (+)- 20 , and (+)- 21 gave, by ionic hydrogenation, the complexes (?)-(3R)- 3 , (+)-(2S,4S)- 10 , (?)-(R,R, S)- 22 , and (?)-(R,R,R)- 23 respectively, with known absolute configurations.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. IV. Synthese von (3R, 3′R, 6′R)-Lutein. Vorläufige Mitteilung

Synthesis of optically active natural carotenoids and structurally related compounds. IV. Synthesis of (3R, 3′R, 6′R)-lutein The synthesis of (3R, 3′R, 6′R)-lutein ( 19 ) according to the building principle C₂₅+C₁₅?C₄₀ is reported utilizing (R)-4-hydroxy-2,6,6-trimethyl-2-cyclohexen-1-one ( 4 ) as a readily available key intermediate.     

Darstellung und Charakterisierung von Bindungsisomeren Bromorhodanorhenaten(IV)

Preparation and characterization of bondisomeric bromorhodanorhenates(IV) The new compounds [ReBr₅(SCN)]^2?, [ReBr₅(NCS)]^2?, cis/tr.-[ReBr₄(NCS)(SCN)]^2?, cis-[ReBr₄(NCS)₂]^2?, mer-[ReBr₃(NCS)₃]^2? are prepared from [ReBr₆]^2? by ligand exchange with NaSCN, KSCN, or (SCN)₂ in organic solvents and isolated by ion exchange chromatography on DEAE cellulose. The bondisomers are significantly distinguished by the frequencies of inner ligand vibrations: v_CN(S) > v_CN(N), v_CS(N) > v_CS(S), δ_NCS δ_SCN. The electronic absorption spectra measured at 10 K exhibit in the region 5700 to 15300 cm^?1 all intraconfigurational transitions (t_2g³) splitted into 8 Kramers doublets by lowered symmetry (C_4v, C_2v, C_s) and spin orbit coupling. The O–O-transitions are deduced form vibrational fine structure and confirmed by electronic Raman bands in some cases. The magnetic moments are in the range of 3.0 to 3.9 B.M.     

Diasteroselektive Hydroxyalkylierungen in 1-Stellung von Tetrahydroisochinolinen und Synthese von Aporphin-, Protoberberin- und Phthalid-Alkaloider

Diastereoselective Hydroxyalkylations in Position 1 of Tetrahydroisoquinolines and Synthesis of Aporphine, Protoberberine, and Pathalide Alkaloids Unsubstituted and 6,7-dialkoxy-N-pivaloyl-tetrahydroisoquinolines 1 – 3 are converted to 1-bromomagnesium derivatives by sequential treatment with t-BuLi (?75°/THF) and MBr₂.OEt₂. Addition of the metalated tetrahydroisoquinolines to aliphatic or aromatic aldehydes occurs with relative topicity ul (Scheme 2). The 1-hydroxyalkylated 2-pivaloyl-tetrahydroisoquinolines a of u-configuration thus obtained (14 examples) can be converted to free aminoalcohols c of either l-or u-configuration (9 examples; Scheme 3). The depivaloylation with retention (→ u-c) is best achieved by heating in EtOH/KOH, the conversion to 1-aminoalcohols l-c by treatment with CF₃COOH/(CF₃CO)₂O (→ l,-pivalates l-b), followed by alkaline saponification or by LiAlH₄ reduction of the esters. The configuration of the products is assigned by ¹H-NMR spectroscopy, by X-ray crystal structure analysis, by chemical correlation, and by comparison of the chemical properties of the l- and the u-isomers. The diastereoselective hydroxybenzylation of the tetrahydroisoquinoline is used for short syntheses of ushinsunine/oliveroline (Scheme 4), β-hydrastine, and ophiocarpine/epiopliocarpine (Scheme 6; aporphine, phthalide, and protoberberine alkaloids, respectively).     

New orthogonally functionalized synthetic blocks from <Emphasis Type="Italic">R</Emphasis>-(−)-carvone

The intramolecular cyclization of (−)-cis-carveol under iodine treatment afforded (1R,5R,6S)-6-iodomethyl-2,6-dimethyl-7-oxabicyclo[3.2.1]oct-2-ene that was subjected to allyl oxydation with the complex CrO₃DMP giving a synthetically valuable building block, (1R,5R,6S)-6-iodomethyl-2,6-dimethyl-7-oxabicyclo[3.2.1]oct-2-ene-4-one. In the latter the double bond was cleaved by ozonization to obtain the expected trioxo derivative, and the subsequent ozonolysis of its enol form provided a multiple functionalized tetrahydrofuran derivative.     

Darstellung,Eigenschaften und Molekülstrukturen von chiralen Dimethylaluminium-aminoalkoxiden

Preparation, Properties, and Molecular Structures of Chiral Dimethylaluminum Amino Alkoxides Dimethylaluminium-2-piperidylmethoxide ( 1 ), N-methyl-3-piperidyloxide ( 2 ), R(–)-2-aminobutoxide ( 3 ) and cis-1 R, 2 S-2-N-benzylaminocyclohexyl-1-methoxide ( 4 ) were obtained by reaction of Me₃Al with the corresponding aminoalkohols in n-pentane. The compounds were characterized by ¹H, ¹³C, and ²⁷Al n.m.r. spectroscopy. The molecular structures of 1 , 3 , and 4 were determined by X-ray diffraction. The compounds form oxygen-bridged dimers and in consequence of an Al–N interaction two additional chelate rings. The bond distances of the central Al₂O₂ ring correspond with 1.9 Å to those of known dialkylaluminumalkoxides. The Al–N bond distances run to 2.18 Å which indicates a strong EDA interaction.