Heterotricyclodecane XVI. 2-Oxa-7-aza-isotwistane und 2-Oxa-7-aza-twistane

The synthesis of several derivatives of 2-oxa-7-aza-isotwistane ( 20–29 and 35 ) and 2-oxa-7-twistane ( 30–34 ) is described starting from cis,cis-cycloocta-1, 5-diene ( 1 ). The bicyclic acetoxy-olefin 10 was used as a key intermediate. The 10^N(7)-isotwistane 22 was treated under reaction conditions suitable for molecular rearrangements involving an oxonium ion g , by neighbouring group participation, leading to 2-oxa-7-aza-twistanes.     

Heterotricyclodecane X. 2-Oxa-7-thia-isotwistan und 2-Oxa-7-thia-twistan sowie Derivate

The synthesis of 2-oxa-7-thia-isotwistane ( 11 ) and 2-oxa-7-thia-twistane ( 22 ) as well as of several of their derivatives is described starting from endo-2-hydroxy-9-thiabi cyclo[3.3.1]non-6-ene ( 4 ). The 10^O(2)-isotwistane bromide 13 , iodide 14 and tosylate 30 as well as the 10^S(7)-isotwistane iodide 15 , tosylate 20 , and the 10^S(7)-twistane tosylate 21 were treated under reaction conditions suitable for molecular rearrangements involving the epi-sulfonium ion i and the oxonium ion g . respectively, by neighbouring group participation.     

Heterotricyclodecane XIX. Umlagerungen von 4,8-disubstituierten 2,6-Dioxa- und 2-Oxa-6-aza-adamantanen zu 4,10-disubstituierten 2,7-Dioxa- und 2-Oxa-7-aza-isotwistanen sowie -twistanen

Rearrangements of 4,8-disubstituted 2,6-dioxa- and 2-oxa-6-aza-adamantanes to 4,10-disubstituted 2,7-dioxa- and 2-oxa-7-aza-isotwistanes as well as -twistanes. Substitutions and rearrangements involving neighboring group participation starting from 4,8-diiodo-2,6-dioxa- and 4,8-diiodo-2-oxa-6-aza-adamantanes ( 5 and 6, 12 and 48 , resp.) were studied, yielding 4,8-disubstituted 2,6-dioxa- and 2-oxa-6-aza-adamantanes ( 7, 9, 39, 42 and 13, 15, 50, 52 , resp.), 4,10-disubstituted 2,7-dioxa- and 2-oxa-7-aza-isotwistanes ( 8, 10, 41, 43 and 14, 16, 51, 53 , resp.) and corresponding-twistanes ( 11 and 17 , resp.).     

Preparation and Reactions of 2-Oxa-6-thiabicyclo[3.2.0]-heptanes and 2-Oxa-5-thiabicyclo[2.2.1]heptanes from Pentoses

Abstract:

The preparation of the two diastereoisomeric 3-methoxy-2-oxa-6-thiabicyclo-[3.2.0]heptan-4-ols 4 and 5 from D-xylose 1 via methyl 2,3-anhydro-α-D-ribofuranoside and the corresponding β-anomer is described. Oxidation of 4 and 5 yields the sulfoxides 6 and 7 and the sulfones 8. – On the other hand, the two diastereoisomeric 3-methoxybicyclo[2.2.1]heptan-7-ols 11 and 12 are obtained from methyl 5-acetylthio-5-deoxy-2-O-mesyl-D-xylofuranosides 9 and 10 via Mitsunobu reaction and intramolecular cyclization. – The stereoisomeric counterparts of 4 and 5, 13 and 14, are obtained in only four steps from L-arabinose.     

Synthesis of a New Spiro System: 1-Oxa-7-thia-4-azaspiro[4.5]decane 7,7-Dioxide

Dihydro-2H-1λ⁶-thiopyran-1,1,3(4H)-trione reacted with N-substituted 2-aminoethanols to give derivatives of a new spiro system, 1-oxa-7λ⁶-thia-4-azaspiro[4.5]decane-7,7-diones. No spirocyclic product was obtained by the reaction with unsubstituted 2-aminoethanol, but the corresponding enamine was formed as in the reactions with other primary amines.     

Oxidative Reactions of Azines. 11. The Influence of Manganese Dioxide on the Reaction of Tetrahydropyridines with Formaldehyde: Synthesis and Molecular Structures of 3-Oxa-7-azabicyclo[3.3.1]- and 6-Oxa-2-azabicyclo[3.2.1]octanes

New derivatives of piperidino[4,5-d]dioxane and 3-oxa-7-bicyclo[3.3.1]nonane were obtained by the oxidatively catalysed condensation of 4-aryl-1,2,3,6-tetrahydropyridines with formaldehyde. The direction of this reaction is sharply altered in the presence of manganese dioxide to give 6-oxa-2-azabicylo[3.2.1]octan-4-one — the product of the oxidative condensation of a new type.     

Heterotricyclodecane XIV. 2-Oxa-6-aza-adamantan und Derivate

The synthesis of 2-oxa-6-aza-adamantane ( 21 ) and several of its derivatives ( 13–20 , 22 , 23 , 25–34 , 37 , and 38 ) was achieved starting from the 9-azabicyclo[3.3.1]nona-2,6- dienes 2 , and 3 , and 9-oxabicyclo[3.3.1]nona-2,6-diene ( 1 ).     

Synthesis and structure of 7<Emphasis Type="Italic">H</Emphasis>-12-Oxa-3,7-diazapleiadenes

The molecular structures of 9,11-di-tert-butyl-2,4-dimethyl-7H-12-oxa-3,7-diazapleiadene and 7-acetyl-9,11-di-tert-butyl-2,4,6-trimethyl-7H-12-oxa-3,7-diazapleiadene were determined by X-ray analysis.     

1,3-Oxathiolan-Synthese: Spirocyclische 1,3-Oxathiolane aus der Lewis-Säure-katalysierten Umsetzung von cyclischen Trithiocarbonaten und Oxiranen

1,3-Oxathiolanc Synthesis: Spirocyclic 1,3-Oxathiolanes from the Lewis-Acid-Catalyzed Reaction of Cyclic Trithiocarbonates and Oxiranes The cyclic trithiocarbonates 1.3-dithiolane-2-thione ( 4 ) and 1,3-dithiole-2-thione ( 9 ) in 1,2-dichloroethane and MeCN, respectively, react with alkyl- and phenyl-substituted oxiranes 2 in the presence of Lewis acids to give 1-oxa-4,6,9-trithiaspiro[4.4]nonanes 5 and 6 (Scheme 2) and 1-oxa-4,6,9-trithiaspiro[4.4]non-7-enes 10 and 11 (Scheme 3), respectively. The reactions proceed regioselectively yielding 2-alkyl ( 5 , 10 ) and 3-phenyl derivatives ( 6 , 11 ) as the main products. From the reaction of 4 and 2-phenyloxirane ( 2e ) with TiCl₄, 2-phenyl-1,4,6,9-tetrathia-spiro[4.4]nonane ( 7 ) is isolated as a minor product. The molecular structures of 5a , 6e , and 7 are established by X-ray crystallography.     

1,3,4-Oxa- und 1,3,4-Thia-diphospholane aus Diphosphorsubstituierten 2-Oxa- und 2-Thia-propanen

1,3,4-Oxadiphospholanes and 1,3,4-Thiadiphospholanes from Diphosphorus-substituted 2-Oxa- and 2-Thia-propanes The synthesis of phosphonates and phosphinates of the type (RO)₂(O)PCH₂ZCH₂P(O)(OR)₂, R¹(RO)(O)PCH₂ZCH₂P(O)(OR)₂ and R¹(RO)(O)PCH₂ZCH₂P(O)(OR)R¹ (with Z = O, S; R = Et, Prⁱ; R¹ = Me, Ph) is reported. Acyclic diphosphanes, R¹(H)PCH₂ZCH₂P(H)R² (with Z = O, S; R¹ = R² = H, Me, Ph; R¹ = H, R² = Me), and 1,3,4-Oxadiphospholanes as well as 1,3,4-Thiadiphospholanes are obtained from the esters by reduction.     

Synthesis and molecular structure of 7<Emphasis Type="Italic">H</Emphasis>-12-oxa-3,7-diazapleiadene-substituted 1,3-tropolones

An acid-catalyzed reaction of substituted 2-methyl-7H-12-oxa-3,7-diazapleiadenes with 1,2-benzoquinones leads to 7H-12-oxa-3,7-diazapleiadene-substituted 1,3-tropolones. Molecular structure of 5,7-di(tert-butyl)-2-[9,11-di(tert-butyl)-4-methyl-7H-12-oxa-3,7-diazapleiaden-2-yl]-4-nitro-1,3-tropolone was established by X-ray crystallography. Energy and structural characteristics of isomeric 5,7-di(tert-butyl)-2-[9,11-di(tert-butyl)-4-methyl-7H-12-oxa-3,7-diazapleiaden-2-yl]-4-nitro-1,3-tropolones in the gaseous phase and a polar solution were studied by the PBE0/6-31G** method.     

Synthesis of 2H-chromeno[2,3-d]pyrimidine-2,4-(3H)-diones (10-Oxa-5-deazaflavins) and their use in the oxidation of benzyl alcohol

Treatment of 6-phenoxyuracil derivatives with the Vilsmeier reagent (dimethylformamide-phosphorus oxy-chloride) gave the corresponding 5-formyl-6-phenoxyuracil derivatives or their equivalents (5-dimethylamino-methylene-6-phenoxyuracil derivatives). Dehydrative cyclization of the above 5-formyluracils or 5-dimethyl-aminomethyleneuracils with polyphosphoric acid gave the corresponding 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones (10-oxa-5-deazaflavins). These 10-oxa-5-deazaflavins showed strong oxidizing power in oxidizing benzyl alcohol even under neutral conditions (without base) to give benzaldehyde, while they were hydro-genated to 1,5-dihydro-10-oxa-5-deazaflavins.     

31P-NMR-Daten heterocyclischer phosphine. Diastereomerenzuordnung an 1,3-Oxa-, 1,3-Aza- und 1,3-thiaphospholanen

The diastereomers of 16 1,3-oxa-, 1,3-aza- and 1,3- thiaphospholanes were assigned by means of the coupling constants ²J(P? C? H) and ³J(P? C? CH₃) and the linewidths of the ³¹P signals and ¹H chemical shifts of CH₃ groups. It is shown that the change in the ³¹P chemical shifts allows the estimation of the relative configuration in these compounds.     

1-Oxa-3-azapentalen-2-ones as Precursors of cis-2-Amino Alcohols: Synthesis from Propargyl Alcohols, CO2, and Amines Using an Intramolecular Amidoalkylation Reaction of Oxazolidin-2-ones

The reaction of 5-methyl-5-(4-methyl-3-pentenyl)-4-methylene-1,3-dioxolan-2-one with primary amines gives the corresponding 4-hydroxy-4-methyloxazolidin-2-ones. These undergo an intramolecular amidoalkylation reaction to form 1-oxa-3-azapentalen-2-ones which are potential precursors of cyclopentanyl cis-2-amino alcohols.     

On the Preparation of 2‐Substituted Cephalosporins,Part 2

Cephalosporin sulfoxides 1 and 2 containing an enone‐ or dienone‐type moiety at position 2 were treated with 2,3‐dimethylbuta‐1,3‐diene or diethyl azodicarboxylate to synthesize, in Diels? Alder reactions, the new cephalosporin derivatives 4 and 5 with a cyclic substituent (Scheme 1). Under the same conditions, ethyl diazoacetate and diazomethane reacted differently: while reactions of 1 and 3 with the former lead to compounds 7 – 10 corresponding to the 1,3‐dipolar cycloaddition route (Scheme 2), diazomethane produced only enol ethers 12 and 13 , respectively (Scheme 3). This difference could be rationalized by assuming two different reaction pathways: an orbital‐symmetry‐controlled concerted cycloaddition and an ionic one.     

Desoxaphomin,das erste [13]Cytochalasan,ein möglicher biogenetischer Vorläufer der 24-Oxa-[14]cytochalasane

From cultures of a Phoma species (strain S 298) the hitherto unknown metabolite deoxaphomine has been isolated. On the basis of the spectral data, structure 1 of the (7S, 16R, 20R)-7,20-dihydroxy-16-methyl-10-phenyl-[13]cytochalasa-6(12),13^t,21^t-triene-1,23-dione is assigned to deoxaphomine. This structure is confirmed by the chemical degradation of 1 , yielding the products 4 and 6 which are identical with derivatives of phomine ( 2 )((7S,16R,20R)-7,20-dihydroxy-16-methyl-10-phenyl-24-oxa-[14]cytochalasa-6(12), 13^t,21^t-triene-1,23-dione) and cytohalasin D ( 8 ) ((7S,16S,18R,21R)-21-acetoxy-7,18-dihydroxy-16,18-dimethyl-10-phenyl-[11]sytochalasa-6(12),13^t,19^t-triene-1,17-dione). Deoxaphomine ( 1 ) is a potential biogenetic precursor of the 24-oxa-[14]cytochalasans. Preliminary results of the biological activity of deoxaphomine are reported.     

Alkylierung in der 2-Stellung von (2S, 4R)- 4-Hydroxyprolin unter Retention

Alkylation in the 2-Position of (2S, 4R)-4-Hydroxyproline with Retention of Configuration O-Acetyl-4-hydroxyproline ( 1b ) is condensed with pivalaldehyde to give a single stereoisomer of the 2-(tert-butyl)-4-oxo-3-oxa-1-azabicyclo[3.3.0]oct-7-yl acetate ( 3 ). This is converted to the enolates 4 or 5 , reactions of which with alkyl halides, aldehydes, and acetone (→ 6,9,10,11 ) are diastereoselective (lk-1,3-induction). Cleavage of the corresponding products furnishes the enantiomerically pure 2-deuterio-, 2-methyl-, 2-allyl-, and 2-benzyl-substituted 4-hydroxyprolines 2a–2d .     

Study of the Steric Structure of 7-Alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and Their Derivatives Using 1H NMR Spectroscopy

Using the ¹H NMR spectroscopic method it has been shown that 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonanes exist in deuterochloroform solution in a double chair conformation. 7-(3-Butoxypropyl)-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol is a 1:1 mixture of the two stereoisomeric alcohols. One of them exists in a double chair conformation having an equatorial hydroxyl group with relation to the piperidine ring and the other in a chair-boat conformation having an axial hydroxyl group which involves an intramolecular hydrogen bond with the unshared electron pair of the nitrogen atom.     

Photochemical Synthesis and Some Reactions of 7-Oxa-and 7-Thiatricyclo[3.2.1.03,6]octan-2-ones

Irradiation (λ = 350 nm) of newly synthesized 2-acetyl- or 2-methyl-2-(alk-2-enyl)furan-3(2H)-ones 1 and 2-acetyl- or 2-methyl-2-(prop-2-enyl)thiophen-3(2H)-ones 2 affords the corresponding 1-acetyl- or 1-methyl-substituted 7-oxa- and 7-thiatricyclo[3.2.1.0^3,6]octan-2-ones 10 and 11 , respectively, via regioselective intramolecular [2 + 2] photocycloaddition in 65–95% yield (Scheme 2). The 1-acetyl-substituted O-derivatives 10b and 10c undergo ring opening on treatment with MeONa in MeOH at–78° to afford stereoselectively methyl 3-exo-acetyl-2-oxabicyclo[3.2.0]heptane-7-endo-carboxylates 12b and 12c , respectively, while a 2:1 diastereoisomeric mixture of methyl 3-acetyl-2-thiabicyclo[3.2.0]heptane-7-endo-carboxylates 13 and 14 is obtained from the corresponding S-derivative 11b . The outcome of the Huang-Minlon reduction of the 1-methyl-substituted ketones 10a and 11a is again influenced by the heteroatom in the tricycle. While 1-methyl-7-oxatricyclo[3.2.1.0^3,6]-octane ( 15 ) is the only product from the corresponding oxatricyclooctanone 10a , a 1:2 mixture of 1-methyl-7-thiatricyclo[3.2.1.0^3,6]-octane ( 16 ) and 3-methylbicyclo[3.1.1]hept-2-ene-6-endo-thiol ( 17 ) is obtained from the analogous S-compound 11a , both products stemming from a common carbanion precursor.     

Two-dimensional NMR studies of 2-substituted thioxanthene sulfoxides

2-Fluoro-, 2-chloro-, 2-bromo-, 2-methyl-, and 2-methoxythioxanthene have been prepared by borane reduction of the corresponding thioxanthone. The corresponding sulfoxides were prepared by m-chloroperoxybenzoic acid oxidation of these sulfides. Proton and carbon chemical shifts have been assigned to these thioxanthene sulfoxides with the aid of LROCSCM and SROCSCM experiments. Carbon chemical shifts in the unsubstituted rings occur at approximately 125 ppm (C5); 128 ppm (C6); 130 ppm (C7); 128 ppm (C8); and 36 ppm (C9). The methylene protons appears as AB doublets at approximately 4.2 and 3.8 ppm. All sulfoxides have the same, pseudo-equatorial geometry.