7-Oxabicyclo heptanes, from

The dicarboxylation of cyclic alkenes is a useful reaction. All-c.vo-methyl-7-oxabicyclo(2.2.1]heptane-2,3,5,6-tetracarboxylate (233) was prepared from the cyclic alkene 232 using Pd on carbon and CuCh in MeOH at room temperature with high diastereoselectivity[216]. The dicarbonylation of cyclopentene... 

The knowledge of the valence tautomerization of benzene oxides to oxepins12 prompted several groups to synthesize oxepins by dehydrohalogenation of 7-oxabicyclo[4.1.0]heptane derivatives. Numerous examples have been described for the base-catalyzed elimination of hydrogen bromide from the 3,4-dibromo-7-oxabicyclo[4.1.0]heptane system. The reaction products are usually obtained as mixtures of oxepin 1 and benzene oxide 2. The 2,7-bis(hydroxy-methyl)oxepin 1 p obtained by this route can be converted to the 2,7-dicarbaldehyde with man-ganese(IV) oxide.23... 

A-Protected 5-aza-2-oxabicyclo[2.2.1]heptanes and their oxo analogs are usually prepared from 4-hydroxyproline or its derivatives in several steps [57JA185 71JHC53, 71N(L)(230)457, 71T961] however, 75 was obtained in a facile one-step transformation involving intramolecular dehydration... 

Likewise, unprotected polyhydroxy compounds can be successfully fluorinated to give the products resulting from substitution of the hydroxy groups by fluorine, wn-o-lnositol reacts with sulfur tetrafluoride and anhydrous hydrogen fluoride at ambient temperature to give a moderate yield of the cyclic sulfite ester of tw/o. cfo-5,6-difluoro-7-oxabicyclo[2.2.1 heptane-e.w,e.vo-2,3-diol (6) and, alter hydrolysis, the free difluoro diol 7.61... 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

A series of copolymers has been made from THF and 7-oxabicyclo-[2 2 l]-heptane using FeCl3-SOCl2 as catalyst. Low molecular weight polymers with melting points ranging from 150 to 320° C were reported (109). 

Twenty-seven two-year-old scaleless hens were transported to Visalia, CA on October 1, 1979, housed in cages overnight with food and water provided ad lib, and exposed to field applications of DEF on October 2. Some birds were repeatedly treated over the next five days. The mature cotton fields (Diversified Farming Inc.) were sprayed from a ground vehicle that treated 8 rows simultaneously with DEF-6 (0.72 kg/l, 6 lb/gal Mobay Chemical Co.) at 0.37 gal/acre and Accelerate (amine salt of endothall (7-oxabicyclo (2.2.1) heptane-2,3-dicarboxylic acid, 0.06 kg/l, 0.5 lbs/gal) at 0.19 gal/acre in 25 gal water/acre. 

The asymmetric hydrolysis of (exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol, diacetate ester (37) to the corresponding chiral monoacetate ester (38) (Fig. 12B) has been demonstrated with lipases [61]. Lipase PS-30 from P. cepacia was most effective in asymmetric hydrolysis to obtain the desired enantiomer of monoacetate ester. The reaction yield of 75 M% and e.e. of >99% were obtained when the reaction was conducted in a biphasic system with 10% toluene at 5 g/liter of the substrate. Lipase PS-30 was immobilized on Accurel PP and the immobilized enzyme was reused (5 cycles) without loss of enzyme activity, productivity, or e.e. of product (38). The reaction process was scaled up to 80 liters (400 g of substrate) and monoacetate ester (38) was isolated in 80 M% yield with 99.3% e.e. The product was isolated in 99.5% chemical purity. The chiral monoacetate ester (38) was oxidized to its corresponding aldehyde and subsequently hydrolyzed to give chiral lactol (33) (Fig. 12B). The chiral lactol (33) obtained by this enzymatic process was used in chemoenzymatic synthesis of thromboxane A2 antagonist (35). 

A number of pyrans, including 3-hydroxy-tetrahydropyran (both axial conformer, 29 and equatorial conformer, 30), 2-methoxy-tetrahydropyran 33, 3-methyl-tetrahydropyran 32, and several 4-substituted tetrahydropyrans, along with 2-methyl-l,3-dioxolane and the rigid cyclic ethers 7-oxabicyclo[2.2.1]heptane and 1,8-cineole, were studied extensively by NMR. These empirical results, in conjunction with the literature data for a variety of acyclic and cyclic ethers, were used to examine the reliability of O-substituent chemical shift models in these systems. The empirical data correlate well with predictions made from the model and it is concluded that ethereal oxygen substituent chemical shifts are due to both steric and electrostatic terms <1998J(P2)1751>. 

The chloromonoadducts are unstable in aqueous solution and lead to intra and/or interstrand diadducts after aquation of the chloride ligand (vide infra). They can also cross-link DNA to proteins either directly or after aquation [25]. The half-life of the monoadducts formed from cisplatin and PtCl(R2-en) (with R2-en = rac-(lS,2S,4.S )-e-W-2-amino-2-(aminomethyl)-7-oxabicyclo[2.2.1]heptane) on DNA at 310K are 2 h 40 30 min and 8 h 20 20 min [49], respectively, a rather long time on the scale of cellular processing . 

Intramolecular cyclopropanations of pendant alkenes are more favorable. Heteroatom-substituted 2-aza- and 2-oxabicyclo[3.1.0]hexanes, together with 2-oxabicyclo[4.1.0] heptanes, can be prepared from chromium and tungsten Fischer carbenes having a tethered alkene chain. An interesting carbene formation via a cationic alkylidene intermediate, nucleophilic addition (see Nucleophilic Addition Rules for Predicting Direction), and intramolecular cyclopropanation is shown in Scheme 59. An intramolecular cyclopropanation via reaction of alkenyl Fischer carbene complex (28) andpropyne was used in a formal synthesis of carabrone (Scheme 60). 

As mentioned before, the AHg, value for the polymerization of 6,8-dioxabicyclo [3.2.1] octane is less negative than that for l,3-dioxolanes. Bicyclo [3.2.1] octane, in which a five-membered ring is fused to a cyclohexane ring at two axial positions, has 51 kJ/mol strain energy. However, from the fact that 7-oxabicyclo [2.2.1] heptane has less strain energy than bicyclo [2.2.1] heptane can be deduced that the strain energy of 6,8-dioxabicydo [3.2.1] octane may also be less than that of bicyclo [3.2.1] octane. 

The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to 2-ex0-3-exo-bis(chloromethyl)-5-[( )-methoxymethylidene]-6-methylidene-7-oxabicyclo[2.2.1]heptane occurs exclusively, within the limit of detectability by H NMR, on the e.vo-face, i.e., from above the plane of the molecule, to give ll6. This is in contrast to the endo-face selectivity reported for a large number of cycloadditions of dienes grafted on to the bicyclo[2.2.1] skeleton (see also Section 7.2.10.3.1). The formation of 7-oxabicyclo[2.2.1]heptane-diazene charge transfer complexes, i.e., the assistance of the ethereal bridge in the cycloaddition, has been invoked to explain the exo-face selectivity. 

Enantiomerically pure 7-oxanorbornenyl derivatives 319, 320, 321, their saponification products (recovery of the chiral auxiliary in the aqueous phase) and ketones (+)-322 and (—)-322 are coined naked sugars of the first generation because they are chirons (= enantiomerically pure synthetic intermediates) like those derived from natural hexoses. Like natural sugars, they are enantiomerically pure. However, unlike natural sugars, they possess three unsubstituted (naked) carbon centers, the substitution of which follows highly stereoselective methods giving polysubstituted 7-oxabicyclo[2.2.1]heptane-2-ones that can be oxidized into the corresponding uronolactones as illustrated below. 

Acetals of (+)-322 are epoxidized into 335 (Scheme 13.90). Acid-promoted ring opening of the epoxides of 335 with participation of the endo OR group leads to the ra/i5 -5,6-dioxy-substituted 7-oxabicyclo[2.2.1]heptan-2-ones 337 [174]. The reaction sequences of Scheme 13.89 applied to 337, and to its enantiomer obtained from (—)-332, generate d- and L-altrose or l- and D-galactose, respectively. 

Shimalactone A 79, a novel polyketide having bicyclo[4.2.0]octadiene and oxabicyclo[2.2.1]heptane units, was isolated from a cultured marine fungus of Emericella variecolor GFIO. Shimalactone A 79 induced neuritogenesis at 10 mg/mL against neuroblastoma Neuro 2A cells. At higher concentration of 20 mg/mL, it showed cytotoxicity against the same cell line. 

Shing, T. K. M., Lee, C. M., Lo, H. Y. Synthesis of the CD ring in taxol from (S)-(+)-carvone. Tetrahedron Lett. 2001,42, 8361-8363. Marchand, A. P., Kumar, V. S., Hariprakasha, H. K. Synthesis of novel cage oxaheterocycles. J. Org. Chem. 2001,66, 2072-2077. Demnitz, F. W. J., Philippini, C., Raphael, R. A. Unexpected Rearrangement in the Peroxytrifluoroacetic Acid-Mediated Baeyer-Villiger Oxidation of trans-3p-Hydroxy-4,4,10p-trimethyl-9-decalone Forming a 7-Oxabicyclo[2.2.1]heptane. Structure Proof and Total Synthesis of ( )-Farnesiferol-C. J. Org. Chem. 1995, 60, 5114-5120. 

To investigate the source of the unexpected cyclization, we combined a precursor 28 that did not have a 4-hydroxy group with the same stable ylide. This produced compound 29 with an oxabicyclo[2.2.1]heptane skeleton via the epoxide 30. Alternatively, the morphinan methyl ether 28 could also react with the stable sulfur ylide derived from trimethylsulfoxonium iodide at room temperature. The definitive intermediate, 6a-epoxide 30, was isolated, and then treated with NaH in DMF at 80 °C to produce the objective bicyclic compound 29 (Scheme 9). 

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