Enzymatic preparation of optically active 7-oxabicyclo[2.2.1] heptane derivatives

Enzymatic resolution of endo-7-oxabicyclo [2.2.1] hept-2-yl butyrates 3 and 5 using lipase from Candida cylindracea led to optically pure bicyclic alcohols and esters being important intermediates for the synthesis of biologically active compounds.     

Synthesis and free radical polymerization of 2-methylene-7-oxabicyclo[2.2.1]heptane

A new monomer, 2-methylene-7-oxabicyclo[2.2.1]heptane ( IV ) was synthesized via four steps. Its structure was confirmed by IR, ¹H-NMR, and ¹³C-NMR spectra as well as elementary analysis. Free radical polymerization and copolymerization of IV were investigated. No homopolymer was obtained due to the effect of allyl inhibition. When IV copolymerized with electron-donor monomers, such as vinyl acetate and stvrene, IV acted as inhibitor for the polymerization of vinyl acetate, but could not inhibit the polymerization of styrene. However, the copolymers of IV with electron-accepting monomers, such as methyl methacrylate, acrylonitrile, or maleic anhydride (MA) were obtained. The contents of IV in the copolymers increased as e values of electron-accepting monomers increased. Strictly alternating copolymer was obtained only in the case of MA and IV . The thermal properties of copolymers were investigated. © 1995 John Wiley & Sons, Inc.     

Über 1.4-Dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptane

Zusammenfassung 2.5-Dialkyl-3.4-dihydro-2H-pyran-2-aldehyde (1 c–1 f) setzen sich mit Acetamid und Essigsäureanhydrid zu 2,5-Dialky-3.4-dihydro-2H-pyran-2-methandioldiacetaten (2 c–2 f), N.N-[(2.5-Dialkyl-3.4-dihydro-2H-pyran-2-yl)-methylen]bisacetamiden (3 c–3 f) und zu 1.4-Dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanen (6 c–6 f) um. Ausdem 3.4-Dihydro-2H-pyran-2-aldehyd (1 a) entsteht unter gleichen Bedingungen kein Oxabicycloheptan. Mit Methylharnstoff reagieren die genannten Pyranaldehyde zu Pyranylmethylenbismethylharnstoffen9 c–9 f.

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1.4-dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanes

2.5-Dialkyl-3.4-dihydro-2H-pyran-2-carboxaldehydes (1 c to1 f) are transformed by acetamide and acetic anhydride to 2.5-dialkyl-3.4-dihydro-2H-pyran-2-methanediol diacetates (2 c to2 f), N.N-[(2.5-dialkyl-3.4-dihydro-2H-pyran-2-yl)-methylen] bisacetamides (3 c–3 f) and to 1.4-dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanes (6 c–6 f). 3.4-dihydro-2H-pyran-2-carboxaldehyde (1 a) is not converted to an oxabicycloheptane under the same conditions. With methylurea the pyranaldehydes mentioned react to pyranylmethylenebismethylureas9 c–9 f.

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Herrn Prof. Dr.M. Pailer zum 60. Geburtstag gewidmet.     

7-oxabicyclo[2.2.1]heptane hydrochloride and hydrofluoride: Quantum-chemical investigation

Structural parameters, IR spectra and energy of H-bonds for binary complexes of 7-oxabicyclo[2.2.1]heptane molecule with molecules of HCl and HF are calculated by quantum-chemical B3LYP/cc-pVTZ method with inclusion to the basis of diffuse “aug”-orbitals of halogen, oxygen and bridgehead hydrogen.     

Synthesis and ring opening reactions of 2-glyco-1,4-dimethyl-3-nitro-7-oxabicyclo[2.2.1]hept-5-enes

The high-pressure asymmetric Diels-Alder reactions of d-galacto- (1a) and d-manno-3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-nitrohept-1-enitol (1b) with 2,5-dimethylfuran (2) afforded mixtures of cycloadducts, from which the (2S,3R)-3-exo-nitro (3a and 3b), (2R,3S)-3-exo-nitro (4a and 4b), and (2R,3S)-1′,2′,3′,4′,5′-penta-O-acetyl-1′-C-(1,4-dimethyl-3-endo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl)-d-galacto-pentitol (5b) were isolated pure. Deacetylation of these compounds led to new chiral mono-, bi-, and tricyclic ethers, being their asymmetric centers arising from the chiral inductor used in the cycloaddition reaction. A ring opening mechanism through a 1-nitro-1,3-cyclohexadiene intermediate has been proposed.     

7-Selenabicyclo[2.2.1]heptane

Thermolysis of a benzene solution of N-[4-(p-(methoxybenzyl)seleno)cyclohexanoyl]-N,S-dimethyldithiocarbonate affords the hitherto unknown 7-selenabicyclo[2.2.1]heptane in 48% conversion and in 20% yield after chromatography. G3(MP2)-RAD calculations predict a rate constant of 5 × 10(4) s(-1) at 80 °C (3.8 × 10(6) s(-1) at 200 °C) for the intramolecular homolytic substitution process involved in this cyclization.     

Synthesis of novel chiral [2.2.1]cryptands incorporating sugars

Chiral N, N'-dimethyl diaza-crown ethers bearing functionalized α-D-gluco-, α-D-galacto-, and α-D-mannopyranoside residues are transformed into the corresponding [2.2.1]cryptands with bis(2-iodoethyl) ether under high-pressure conditions and subsequent demethylation. Alternatively, α-D-manno-diaza-18-crown-6 reacts with diglycolic acid dichloride under high-dilution conditions to form bisamide which is reduced to the corresponding chiral [2.2.1]cryptand.     

Copolymers of 7-oxabicyclo[2.2.1] heptane with 1,3-dioxane and promesogenic telechelic oligomers thereof

Copolymers of 7-oxabicyclo[2.2.1] heptane (B) (and of its 2-methyl derivatives) with 1,3-dioxane (D) were obtained by cationic copolymerization initiated with benzoylium hexafluoroantimonate. Structure of copolymers was determined by ₁H- and ₁₃C-NMR. The proportion of the acetal bonds in copolymers was additionally confirmed in studies of the products of hydrolysis (only the acetal bonds hydrolyze). D is unable to homopolymerize for the thermodynamic reasons and therefore mostly pseudoperiodic copolymers (-DB_x-)_y are formed. Nevertheless, the reshuffling reactions are responsible for the appearance of “wrong” units. These are: the separate oxymethylene and oxy-1,3-propylene units (P, subunits of D) located between two B units. Only the acetal bonds are cleaved in the acidic hydrolysis with dilute HCl. This gives the promesogenic telechelic oligomers of mostly HO-P-B_x-OH structure. This article is the first to describe successful cationic copolymerization of a cyclic acetal with a cyclic ether. Moreover, the inability of D to homopolymerize gives the thermodynamic basis of the pseudoperiodic copolymer formation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 1733–1742, 1997     

Synthesis of n-heteroaryl-7-azabicyclo[2.2.1]heptane derivatives via palladium-bisimidazol-2-ylidene complex catalyzed amination reactions

[reaction in text] A one-step approach to novel N-heteroaryl-substituted-7-azabicyclo[2.2.1]heptanes from readily available heteroaryl halides and 7-azabicyclo[2.2.1]heptane has been achieved. The cross-coupling amination reaction employs palladium-bisimidazol-2-ylidene complexes as catalysts to give good to moderate yields over a wide variety of substrates.     

Synthesis of 7‐azabicyclo[2.2.1]heptane derivatives by transformation of tropinone

The bromination (CuBr₂, AcOEt/CHCI₃) plus Favorskii rearrangement (EtONa, EtOH) of N‐carbethoxytropinone ( 4 ), readily available from tropinone ( 3 ), affords mixtures of exo‐ and endo‐isomers of 2,7‐dicarbethoxy‐7‐azabicyclo[2.2.1]heptane ( 1b ) in variable and moderate chemical yield (maximum 37%). The bromination (Br₂, HBr/AcOH) reaction of compound 4 gives ethyl trans‐2,4‐dibromo‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate ( 5 ) in 99% yield, a product that on Favorskii rearrangement (EtONa/EtOH) affords ethyl 2,2‐diethoxy‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate in moderate yield ( 6 ) (52%).     

Pauson-Khand reaction of 7-oxabicyclo[2.2.1] systems

The amine oxide-promoted Pauson-Khand cycloaddition of 7-oxanorbornene and norbornadiene derivatives affords easily oxa-bridged bicyclic cyclopentenones with satisfactory 60-80% yields.     

Synthesis and Diels-Alder Reactivity of 1-(Dimethoxy)methyl-2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane. Preliminary communication

A short synthesis of the title compound 13 is reported. The acetal group in 13 enables one to control the regio- and stereoselectivity of the two successive Diels-Alder additions of the tetraene. The first addition is significantly faster than the second one, thus making 13 a versatile reagent for regio- and stereoselective ‘tandem’ cycloadditions.     

Regioselective electrophilic additions to 2-alkoxy- and 2-alkoxymethyl-7-oxabicyclo [2.2.1] hept-5-ene derivatives

The influence of the stereochemistry at C-2 on the selectivity of the reaction between PhSeBr and 2-alkoxymethyl substituted oxanorbornenes has been studied. All endo isomers displayed complete regio- and stereocontrol with incorporation of the electrophile on C-5.     

Synthesis of 1-methyl-3-oxo-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid methyl ester

A simple and efficient method for the preparation of 1-methyl-3-oxo-7- oxabicyclo[2.2.1]hept-5-en-2-carboxylic acid methyl ester (1) is described. The first step is a highly regioselective Diels-Alder reaction between 2-methylfuran and methyl-3-bromo- propiolate. A remarkably difficult ketal hydrolysis reaction was effected by treatment with HCl, a simple reagent that was shown to be more efficient, in this case, than commonly used more elaborate methods.     

N-Arylmethyl-7-azabicyclo[2.2.1]heptane derivatives: synthesis and reaction mechanisms

N-Arylmethyl-7-azabicyclo[2.2.1]heptane (I) derivatives have been synthesized by deprotection of N-protected, N-(arylmethyl)cyclohex-3-enamines, bromination of the resulting secondary cyclohex-3-enamines, followed by base-promoted cyclization (route a), or by bromination of N-protected, N-(arylmethyl)cyclohex-3-enamines followed by deprotection and base-mediated cyclization (route b). In these protocols we have observed that the bromination of the key intermediates (12, 13, and 19) is stereoselective leading to major trans-3-cis-4-dibromides (14, 17, and 20), whose mild base-mediated heterocyclization (on compound 14), or the two-step acid hydrolysis plus base-promoted cyclization (on compounds 17 and 20), gave products 6 and 7 in good yield. A mechanistic investigation using DFT has been carried out to explain the results observed in this work.     

Synthesis of Polypropionate Fragments Containing Tertiary-Alcohol Moieties. Cross-aldolisations with lithium enolates of 7-oxabicyclo[2.2.1]heptan-2-one derivatives

The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1′R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′R)-camphanate ((+)- 1 )) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L -glycero- ((+)- 6 ) and -D -glycero-L -altro-heptono-1,4-lactone ((+)- 7 ), into (?)-(3R,4R,5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((?)- 22 ), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)- 34 ). Condensation of ((+)- 34 with the lithium enolate of (?)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1] heptan-2-one ((?)- 38 ; derived from (+)- 1 ) gave a 3:2 mixture of aldols (+)- 39 and (+)- 40 (mismatched pairs of a α-methyl-substituted aldehyde and (E)-enolate) whereas the reaction of (±)- 34 with (±)- 38 gave a 10:1 mixture of aldols (±)- 41 and (±)- 39 . A single aldol, (?)- 44 , was obtained to condensing (+)- 34 with the lithium enolate of (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)- 43 ; derived from (?)-(1S,2R,4S)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′S)-camphanate ((?)- 3 )). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α-methyl-substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin-Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.     

Synthesis of purine nucleosides built on a 3-oxabicyclo[3.2.0]heptane scaffold

The photochemical [2 + 2] cycloaddition of chiral 3-chloro and 3-fluoro-5-hydroxymethyl-2(5H)-furanone to ethylene and acetylene has been studied. The effect of the halogen atom on the chemical yield and facial diastereoselectivity of the cycloaddition process has been evaluated. From the major anti cycloadducts, practical syntheses of several purine cyclobutane and cyclobutene-fused nucleosides containing a halogen atom have been developed. The anti-HIV activity of the new nucleoside analogues has been evaluated.     

对映体纯1-甲基-7-氧杂双环[2.2.1]庚烷-2-酮的制备

1-甲基 - 7-氧杂双环 [2 .2 .1 ]庚烷 - 2 -酮 ( 1 )是萜类天然产物全合成中的重要中间体 ,能被广泛地应用于多种桉烷 ( Eudesmane)、沉香呋喃 ( Agarofuran)和降胡萝卜素 ( Norcarotenoids)等倍半萜天然产物的全合成[1,2 ] .我们以对映体纯化合物 1为原料 ,实现这类天然产物的不对称全合成 [3～ 6 ] .消旋的化合物 (± ) - 1可以 2 -甲基呋喃和 2 -氯丙烯腈为原料 ,经 3步反应得到 [2 ] .但对映体纯化合物 1的制备尚未见报道 .本文用化学拆分方法 ,成功地制备了对映体纯的 ( + ) - 1和 ( - ) - 1 ,并确定了其绝对构型 .1　结果与讨论为减…