The regiochemistry of intramolecular n-alkenylnitrone additions: preparative and mechanistic implications

The opposite regiochemistry, observed for the reactions $\text{7a}$ → $\text{8a}$ and $\text{7d}$ → $\text{8d}$, as compared with additions $\text{7b}$ → $\text{9b}$, $\text{7c}$ → $\text{9c}$ and $\text{7e}$ → $\text{9e}$, supports the hypothesis that in the transition state of nitrone-olefin additions the new C,C bond is more advanced than the C,0, bond. Further examples show the superimposition of substituent effects on this intramolecular control.     

A convenient synthesis of flindersine,atanine and their analogues

A new synthesis of the pyranoquinolone alkaloids flindersine ($\text{8a}$), 8-methoxyflindersine ($\text{8c}$), N-methylflindersine ($\text{9a}$), zanthobunglanine ($\text{9c}$) oricine ($\text{9d}$) and veprisine ($\text{9e}$) and the prenylquinolone alkaloids atanine ($\text{13a}$), preskimmianine ($\text{13e}$) N-methylatanine ($\text{14a}$), O-methylglycosolone ($\text{14c}$) and N-methylpreskimmianine ($\text{14e}$) is described.     

Cycloaddition reactions of 1,3-benzothiazines - 6. Reactions of 1,3-benzothiazine derivatives with substituted acetyl chlorides

6, 7-Dimethoxy-2$\text{H}$-l,3-benzothiazine derivatives ($\text{1}$, $\text{8}$) react with substituted acetyl chlorides to give angularly condensed β -lactams ($\text{3a}$-$\text{d}$, $\text{10}$, $\text{11}$). The $\text{cis}$ compound $\text{11}$ was epimerised to the $\text{trans}$ derivative $\text{12}$. From the interaction of 2-phenyl-6,7-dimethoxy-4$\text{H}$-1,3-benzothiazine ($\text{7}$) and α -chloro-phenylacetyl chloride two stereoisomeric β -lactam derivatives ($\text{9a}$, $\text{b}$) were isolated, whereas in the other cases studied the reactions leading to β -lactams proved to be stereospecific. Analogous reactions of $\text{4}$-methyl-6,7-dimethoxy-2$\text{H}$-l,3-benzothiazine ($\text{5}$) furnished the enamides $\text{6a}$,$\text{c}$, $\text{d}$. Structures of the new compounds and configurations of the diastereomers were elucidated by IR and NMR spectroscopy.     

Synthesis of streptococci phosphatidyl-α-diglucosyldiglyceride and related glycolipids : Application of the tetraisopropyldisiloxane-1,3-diyl (tips) protecting group in sugar chemistry. Part V

A short and convenient synthesis of phosphatidyl-α-diglucosyldiglyceride (i.e. compound $\text{8d}$) and two related Streptococci glycolipids (i.e. compounds $\text{6a}$ and $\text{6b}$) will be presented. 4',6'-Tetraisopropyl-disiloxane-1,3-diyl (TIPS) protected α-glucosyl diglyceride (i.e. compound $\text{2}$) turned out to be a suitable protected precursor. Thus, compound $\text{2}$ was selectively condensed with glucosyl bromide $\text{3}$ to afford $\text{4}$. Removal of the protecting groups from $\text{4}$ gave glycolipid $\text{6a}$. The “dynamic” properties of the TIPS pro- tecting group were utilized to convert 4',6'-TIPS protected $\text{4}$ into 3',4'- TIPS protected derivative $\text{5a}$. Compound $\text{5a}$ could then be condensed with either a stearoyl fatty acid or a phosphatidyl moiety to give the fully protected derivatives $\text{5c}$ and $\text{8a}$, respectively. Finally, removal of all the protecting groups from $\text{5c}$ and $\text{8a}$ afforded the glycolipid $\text{6b}$ and glycophospholipid $\text{8d}$, respectively.     

The synthesis of γ-fluoroisoleucine

Condensation of 3-fluoro-2-butanone ($\text{2}$) with alkyl diethylphosphonoacetates ($\text{4a–d}$) gave alkyl 4-fluoro-3-methyl-2-pentenoates ($\text{5a–d}$). Addition of bromine yielded alkyl-2,3-dibromo-4-fluoro-3-methylpentanoates ($\text{6a,b}$) which were dehydrobrominated to alkyl 2-bromo-4-fluoro-3-methyl-2- pentenoates ($\text{7a,b}$). Since these compounds could not be hydrogenated to the desired alkyl 2-bromo-4-fluoro-3-methylpentanoates ($\text{8a,b}$), another route was taken. The esters $\text{5a–d}$ were hydrogenated to alkyl 4-fluoro-3- methylpentanoates ($\text{11a–c}$) which were converted to their carbanions. Treatment with bromine gave esters $\text{8a–c}$, and iodine gave alkyl 4-fluoro-2-iodo- 3-methylpentanoates ($\text{12a,b}$). Esters $\text{8a–c}$ and $\text{12a,b}$ were converted to alkyl 2-azido-4-fluoro-3-methylpentanoates ($\text{13a–c}$) whose hydrogenation gave alkyl 2-amino-4-fluoro-3-methylpentanoates ($\text{14a–c}$). Hydrolysis afforded γ-fluoroisoleucine ($\text{1}$).     

Synthesis of phosphatidyl-β-glucosyl glycerol containing a dioleoyl diglyceride moiety : Application of the tetraisopropyldisiloxane-1,3-diyl (tips) protecting group in sugar chemistry. part IV

The preparation of phosphatidyl-β-glucosyl diglyceride $\text{12c}$ is described. The synthesis of glycophospholipid $\text{12c}$ was accomplished by using: (a) the levulinoyl group for the temporary protection of the glucose hydroxyl functions of $\text{6b}$, which could then be converted into the dioleoyl substituted derivative $\text{7c}$; (b) the tetraisopropyldisiloxane-1,3-diyl (TIPS) group to protect the 3'- and 4'-hydroxyl groups of $\text{7c}$, in a two step procedure, to afford compound $\text{8}$; (c) a 2,4-dichlorophenyl protected phosphatidic acid derivative $\text{11}$. Compound $\text{11}$ could be selectively coupled to the primary hydroxyl function of $\text{8}$ to afford the fully protected glycophospholipid $\text{12a}$. Finally, removal of the 2,4-dichlorophenyl and TIPS protecting groups from $\text{12a}$ was performed with syn-4-nitrobenzaldoximate and fluoride ions, respectively, to afford glycophospholipid $\text{12c}$.     

The facile (<−50°C) formation of cis-bicyclo[6.1.0]nona-2,4,6-trienes from cyclonona-1,3,5,7-tetraenes: A symmetry - forbidden reaction

The formation of the $\text{cis}$-bicyclo [6.1.0] nona-2,4,6-trienes $\text{4a}$-$\text{c}$ is not due to the sequence $\text{1}$ → $\text{2}$ → $\text{4}$, which would involve the symmetry-forbidden reaction $\text{2}$ → $\text{4}$ even at ?50°C. Rather, reaction of RX at C^4–7 of $\text{5}$, which is formed together with $\text{1}$, leads (probably via $\text{6a}$-$\text{c}$ and $\text{7a}$-$\text{c}$ to $\text{4a}$-$\text{c}$.     

Synthesis and 13C nmr characterization of some π-excessive heteropolyaromatic compounds

Several π-excessive heteropolyaromatic compounds, which contain furan and thiophen ring and are possible antifungal agents, have been synthesized in good yields according to two general methods. The first method has been used to prepare compounds possessing thiophens linked by their 2- and 5-positions, such as the ter-aryls $\text{2b}$, $\text{2d}$ and $\text{2a}$. Two precursors of these compounds have been obtained either by the Glaser reaction, or using a novel Pd-mediated reaction. The second method,which consists of the Ni-or Pd-catalyzed heteroarylation of heteroarene halides via cross-coupling with heteroaryl Grignard reagents or zinc halides,has been used to prepare the bi-aryls $\text{1a-e}$, which contain two heteroaromatic units, and the ter-aryl $\text{2c}$. Compound $\text{1e}$ has been also prepared starting from 2-(2-thienyl) furan ($\text{1c}$) by selective lithiation, followed by bromination.The ¹³C NMR signals of $\text{1a-e}$ and $\text{2a-d}$ have been assigned on the basis of the literature data and by relaxation measurements. Relaxation data have been also used to obtain qualitative informations on the conformational equilibria of the bi-aryls $\text{1a}$, $\text{1c}$ and the ter-aryls $\text{2a-d}$.     

Die bildung von anellierten und überbrückten produkten bei der intramolekularen cycloaddition von carbonyl-yliden synthese eines “inside-outside”-bicyclo[13.2.1]octadekans

Intramolecular cycloaddition reactions of carbonyl ylides with ester-activated CC-bonds are studied. Whereas the annelated adducts $\text{7}$/$\text{8}$ are formed in the case of $\text{4a}$-$\text{c}$ (n=1, 3, 5) as starting materials, thermolysis of $\text{4d}$ (n=10) leads predominately to the bridged compound $\text{9d}$.     

Molecular rearrangements of 5-azido substituted 1,2,3-triazoles

5-Azido-4-methoxycarbonyl-1-phenyl-1,2,3-triazole ($\text{8a}$) and its phenyl substituted derivatives $\text{8b}$,$\text{c}$ rearrange at 60–80°C to give tetrazolyldiazoacetates $\text{9}$, which have been isolated. When the reactions are allowed to go to completion, products derived from the diazo compounds are obtained; i.e. norcaradienes ($\text{10}$) from benzene solutions and imidazotetrazoles ($\text{12}$) from nitrite solutions. The latter decompose photochemically into diazacyclopentadienonimines ($\text{13}$). A kinetic study of the rearrangement $\text{8}$ → $\text{9}$ has been carried out and the mechanism (Scheme VI) is discussed in comparison with the Dimroth rearrangement.     

Aromatisierung von cytclohexenon-derivaten über selenorganische zwischenstufen

Reaction of the hydroaromatic compounds ($\text{1a}$) and ($\text{3a}$) with lithium-diisopropylamide followed by phenylselenenyl chloride gives the selenides ($\text{1b}$) and ($\text{1c}$) resp. ($\text{3b}$), which form exclusively the phenols ($\text{4}$) resp. ($\text{6}$) after oxidation with 3-chloroperbenzoic acid in the presence of 3,5-dimethoxyaniline ($\text{7a}$).     

Cleavage and some modifications of the 7-amide group of the cephamycins

The cleavage and some modifications of the 7-amide group of cephamycins are described. Cephamycin derivatives 16b, c which were synthesized from the naturally occurring cephamycin C (16a) were converted to the corresponding oxamic acid derivatives 17a, e respectively by the reaction with oxalyl chloride and successive treatment with water. The reaction of the oxamic acid 17a with diphenylcarbodiimide gave 7-aminocephamycinoic acid (7-ACMA) benzhydryl ester (21a) which was further converted to cefoxitin (21c). These compounds 17a, b, c, d, e, f thus obtained from cephamycin C appear to be favorable intermediates for the syntheses of cephamycin analogues such as cefmetazole (28c).     

Acetoacetanilides in Heterocyclic Synthesis,Part 1: An Expeditious Synthesis of Thienopyridines and Other Fused Derivatives

3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}butanamide 1 reacts with arylidinecyanothioacetamide in refluxing ethanolic TEA to give the pyridinethione 2 rather than thiopyrane 4. Compound 2 reacts with α-haloketones to give the s-alkylated derivatives 7a–e. Compound 7a–e undergoes cyclization into thieno[2,3-b]pyridine derivatives 8a–e. The saponification of 8a gives the amino acid 9, which affords 10 when refluxed in Ac₂O. The treatment of 10 with NH₄OAc/AcOH gives 11. Compound II is also obtained when 8e is refluxed in Ac₂O. The reaction of 8a with hydrazine hydrate gives 12 and with formamide gives 13. Compound 13 also is obtained from the reaction of 8e with triethylorthoformate. The acetylation of 8a with Ac₂O gives the amide derivative 14, which, on treatment with aromatic amines, affords 15a–c. Compounds 15a–c are cyclized with H₂SO₄ to 16a–c. Compound 16 is obtained also from the acetylation of compound 8c, d by Ac₂O. Reactions of compound 8e with CS₂ in refluxing dioxane afford 17. The diazotization and self-coupling of 8e give the pyridothienotriazine 18. Finally, the chloronation of compound 13 with POCl₃ affords the chloride derivative 19.     

Stereo- and regioselective methods for the synthesis of three consecutive asymmetric units found in many natural products

Regio- and stereoselective methods are described for the synthesis of compounds possessing the stereochemistry of type $\text{1a}$, $\text{1b}$, $\text{1c}$, and $\text{1d}$ from the aldehyde $\text{2}$.     

Syntheses and thermal reactions of 2-alkyl(or aryl)-1-benzoyl-3,4-dihydro-2-thianaphthalenes

1-Benzoyl-2-methy1-3,4-dihydro-2-thianaphthalene ($\text{4a}$) underwent novel intermolecular 1,4-rearrangement in refluxing toluene to give an enol ether $\text{5a}$, while rearrangement of 2-phenyl derivative $\text{4e}$ proceeded intramolecularly in refluxing xylene to afford a 1,4-rearranged enol ether $\text{5b}$. On the other hand, ylides $\text{4a–e}$ were refluxed in alcohols to afford some ring-opened products $\text{10–12}$.     

Photochemistry of N-aryl-2(1H)-pyrimidin-2-ones

Irradiation of N-aryl-2(1H)-pyrimidin-2-ones ($\text{3a}$-$\text{c}$) in a mixed benzene-alcohol solution afforded the products initiated by Type I cleavage, 1-(3-alkoxycarbonylamino-2-propene)-N-arylimines ($\text{4a}$-$\text{c}$, $\text{5}$, and $\text{6}$) in 45–51% yields.     

Synthesis of 3,3,3-trifluoropropionic and 4,4,4-trifluoro-2-ketobutyric acids

Trifluoroethyl cyclohexyl ketone ($\text{4}$) is prepared by acylation of difluoroethylene ($\text{2}$) with cyclohexanecarboxylic acid chloride ($\text{1}$), followed by Cl→F exchange with potassium fluoride in the presence of triethylbenzyl- ammonium chloride. Bayer-Villiger oxidation of ketone ($\text{4}$) with trifluoroperacetic acid gives cyclohexyl trifluoropropionate ($\text{5}$). 3,3,3-trifluoropropionic acid ($\text{6}$) is obtained by treatment of ($\text{5}$) with trimethylsilyl iodide. Condensation of 2,2,2-trifluorodiazoethane ($\text{7}$) with ethyl glyoxylate ($\text{8}$) gives mainly ethyl 4,4,4-trifluoro-2-ketobutyric acid ester ($\text{9}$) which leads after hydrolysis to the corresponding acid ($\text{12}$).     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

Dimetalated tertiary succinamides. Synthesis of several classes of lignans including the mammalian urinary lignas enterolactone and enterodiol

Reaction of dimetalated succinamides with benzyl halides and aromatic aldehydes provides short routes to diverse lignan natural products $\text{2}$, $\text{3}$, and $\text{4a}$, including the human urinary metabolites ($\text{3d}$) and ($\text{2e}$).