2-Oxabicyclo- -octane

Cycloadditions and Rearrangements. The addition of 2-oxyallyl cations to furan provides a route to oxabicyclo[3,2,l]octanes complementary to the cycloaddition of cyclopropanones to furan. Careful experimental studies have led to yields of preparative importance both with furan and with cyclopentadiene. Following the route to azabicyclo-octanes, dipolar addition to the pyrylium betaine (99) affords oxa-analogues (Scheme 23). Also reported are the addition of fiiran to 1-cyanonaphthalene, the formation of various cycloadducts of tropone and tropolone (Scheme 24), and the phototransformations of (100) (Scheme 25) and (101) (Scheme 26). Thermal addition gives (102) from (103) and similarly other 8-oxabicyclo-octanes are prepared from acyclic precursors. ... 

When treated with fuming sulfuric acid and then with water, decafluoro-cyclohepta-1,4-diene gives hexafluoro-l,5-dihydroxy-8-oxabicyclo(3 2 l)octan-3-one rather than octafluorocyclohepta-2,6-dienone, which is a probable intermediate [28] (equation 31)... 

Tlie thermal reaction of dithiiranes is of particular interest in relation with the dithiirane/thioketone 5-sulfide manifold. Heating 5-oxodithiiranes (4) in solution led to both isomerization to 6,7-dithia-8-oxabicyclo[3.2.1]-octanes 74 and desulfurization to 5-oxothiones 75, the ratio of which was dependent on the reaction conditions employed. The intramolecular [3 + 2] cycloaddition of the thioketone 5-sulfide 76, generated by ring-opening, provides a straightforward explanation for the formation of 74. Meanwhile, 75 is probably formed by a nucleophilic attack on the sulfur atom by another molecule of 4 and/or by elemental sulfur formed during the reaction. 

In the same manner, the reactions of 5-isonitroso-l,3,3-trimethyl-2-oxabicyclo-[2.3.3]octan-6-one hydrazone 142 and 4-isonitroso-2,2,5,5-tetramethyltetrahy-drofuran-3-one hydrazones 143 with the corresponding orthobenzoates result in... 

Trimethylolpropane, el 83 Trimethylolpropane triacrylate, el 14 Trimethylolpropane trimethacrylate, el 85 l,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane, c277... 

Few structures have been solved for this kind of compound. A crystal structure of (2-R,5R,2 R,5 R)-bi(2,2 - / -butyl-1,1 -aza-3,3 -oxabicyclo[3.3.0] octan-4,4 -one prepared from the diastereoselective dimerization of the pivaloyl oxa-zolidin-5-one derivative of proline has been obtained for the determination of the absolute stereochemistry of the C-a atoms of compound 265. 

S. (2R,5S)-2-tert-Butyl-5-methyI-l-aza-3-oxabicyclo[3.3.0Joctan-4-one. In a 250-mL, round-bottomed flask equipped with a magnetic stirrer, 18.3 mL (0.131 mol) of diisopropylamine (Note 10) is mixed with 120 mL of dry tetrahydrofuran (THF, Note 11) under argon. At -78°C bath temperature, 88.6 mL of a 1.6 M solution of butyllithium (0.142 mol) in hexane is added and the mixture is allowed to warm to room temperature for 20 min. After the mixture is recooled to -78°C, the lithium diisopropylamide (LDA) solution is added over a period of 20 min (Note 12) to a Solution of 20.0 g (0.109 mol) of (2R,5S)-2-tert-butyl-l-aza-3-oxabicyclo[3.3.0]octan-4-one in 600 mL of dry THF in a 1-L, round-bottomed flask, precooled to -78°C. Tetrahydrofuran (20 mL) is used to rinse the 250-mL flask. After keeping the resulting solution at -78°C tor 45 min, 8.8 mL (0.142 mol) of iodomethane (Note 13) is added Over a period of 10 min. The resulting mixture is allowed to warm to 0°C over a period Of 3 hr, and 300 mL of a saturated aqueous solution of ammonium chloride is added. 

Lewis acid catalyzed reaction of oximes 172 (equation 113) with divinyl ketone (173) provided l-aza-7-oxabicyclo[3.2.1]octan-4-ones 174 through a sequential Michael addition and [3 + 2] cycloaddition. The reaction occurred with complete stereoselectivity giving the same product with both cis- and frawi-oximes . 

Hydrazone formation of pyridazine-3-hydrazines with aldoses, dialdofuranoses, and dialdopyranoses was studied by Stanovnik and co-workers. The respective hydrazones could be cyclized with Bt2 in MeOH or Pb(OAc)4 to j-triazolo[4,3-3]pyridazin-3-yl substituted polyols <1997JHC1115, 1998JHC513>. Similarly, 4-[(dimethylamino)-methylene]-l,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one was reacted with pyridazine-3-hydrazines and the resulting mixtures were subsequently treated with Pb(OAc)4. Besides j-triazolo[4,3-3]pyridazine formation also diazenes were obtained. This can be rationalized by the enehydrazine-hydrazone mixtures observed in the first reaction. For phthalazin-l-hydrazines only diazenes were obtained after oxidation <2005TA2927>. Also cyclizations of... 

The cyclization of tetrahydropyran 12 to 5-methyl-8-oxabicyclo[3.2.1]octan-6-one (13) is a particularly striking example of C-H activation by an adjacent heteroatom59. Although the ring size would be the same, and conformational differences in the transition states leading to both products should be minimal, none of the alternative bicyclic ketone 14 was observed. 

Irradiation of 2-(prop-2-enyloxy)- and 2-(but-2-enyloxy)cyclohex-2-enones gives 2-oxabicy-clo[2.1.1]hexane and -[3.1.1]heptane derivatives, respectively,17 while 2-(but-3-enoyIoxy)- (7, n = 1) and 2-(pent-4-enoyloxy)cyclohex-2-enone (7, n = 2) afford the cyclohexanone-annulated 2-oxabicyclo[3.2.0]heptan-3-one (8, n = 1) and -[4.2.0]octan-3-one (8, n = 2) derivatives, respectively.18... 

The intramolecular version of this reaction has also been shown to be successful. For example, the carbene complex 2 was transformed to l-methyl-2-oxabicyclo[4.2.0]octan-8-one (3) in 86% yield under anaerobic conditions.9... 

It has also been reported that ozonolysis of 6-methyl-8-mcthylcne-m-3-oxabicyclo[4.2.0]octan-2-one in methanol gave methyl 2-(4-methyl-2-oxo-4-tetrahydropyranyl)acetate by retro-Claisen reaction, whereas in dichloromethane 6-methyl-ra-3-oxabicyclo[4.2.0]octane-2,8-dione was isolated in good yield (see Section 5.1.3.).16... 

Moreover, reaction of 6,6-dimethylbicyclo[3.1, l]heptan-2-one with an aqueous suspension of magnesium monoperoxyphthalate at 80 °C gave 7,7-dimethyl-2-oxabicyclo[4.1.1]octan-3-one in only 0.5 % yield,24... 

Nearly all examples of epoxidation of alkylidenecyclobutanes involve 3-chloroperoxybenzoic acid.15 58-70 This is because the conditions are mild, the workup is easy and few byproducts are formed. Generally, dichloromethane or chloroform is used as solvent. Solid sodium hydrogen carbonate is occasionally added to avoid acid-catalyzed rearrangement of the spiro compound. For example, 6-isopropylidene-l,4,4-trimethylbicyclo[3.2.0]heptan-3-one reacted with 3-chloroperoxybenzoic acid and sodium hydrogen carbonate to give 2,2,3, 3, 6-pentamethyl-spiro[3-oxabicyclo[4.2.0]octane-8,2 -oxirane]-4-one (4) in quantitative yield. However, without the use of sodium hydrogen carbonate, substantial amounts of 2,2,6,9,9-pentamethyl-3-oxa-bicyclo[4.3.0]nonane-4,8-dione (5) and 2,2,6,8,8-pentamethyl-3-oxabicyclo[4.3.0]nonane-4,9-dione (6) were also formed.15-64... 

It is interesting to note that adducts having the 8-oxabicyclo[3.2.1]octane... 

Formation of a six-membered ring by cyclization of a,y-carboxylic acid groups is also observed in the reaction of sulfur tetrafluoride with (1 / , S)-( + )-camphoric acid besides 1,2,2-trimethyl-3-(trifluoromethyl)cyclopentanecarbonyl fluoride (20) and camphoroyl difluoride (21). the bicyclic tetrafluoro ether, 2,2,4,4-tetrafluoro-l,8,8-trimethyl-3-oxabicyclo[3.2.1]octane (22). is formed. The ratio of products strongly depends on the reaction conditions.250... 

A. Warm and P. Vogel, Helv. Chim. Acta 70 690 (1987). An improved synthesis of (lS,4S)-7-oxabicyclo[2,2.1]hept-5-en-2-one starting from a new chiral auxiliary, methyl (1 S,5R,7S)-3-eihyl-2-oxo-3-aza-6,8-dioxabicyclo[3.2.1 ]octane-7- o-carboxylate (obtained from di-O-acetyl-(SyS)-tartaric anhydride and W-ethylaminoethanol ethyl acetal), was reported J.-L. Reymond and P. Vogel, Tetrahedron Asymm. 7 729 (1990). 

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