8-Oxabicyclo octane ring

A novel intramolecular alkylation using a spiroketal (14) with BFj.OEt, in THF at reflux forms the benzene-fused 8-oxabicyclo[3.2.1]octane ring system (15) in satisfactory yield. IV-Tosylpipecolinic acid (16) in the presence of sulfuric acid in benzene forms the unexpected aromatized derivative (17) in 18% yield and the mechanism is suggested to involve the reaction of intermediate (18) with benzene to form (19). Cumyl and r-butyl hydroperoxides have been used for the electrophilic alkylation of activated aromatic substrates, mainly phenols and phenol ethers.The hydroperoxides behave differently as far as catalysis and regioselectivity are concerned. The latter is believed to be explicable by steric and reactivity/selectivity considerations. Electrophilic r-butylation may be followed by radical reactions due to the r-butyl... 

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. 

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. 

Due to the ring strain in the cyclobutane ring, /(-carbonyl cyclobutanones made by oxidation of methylenecyclobutane in methanol will readily undergo retro-Claisen-type reactions. For ozonolysis, this can be avoided by changing the solvent from methanol to dichloromethane treatment of 6-methyl-8-methylene-m-3-oxabicyclo[4.2.0]octan-2-one with ozone in methanol gave methyl 2-(4-methyl-2-oxo-4-tetrahydropyranyl)acetate (1), while the same treatment in dichloromethane gave 6-methyl-m-3-oxabicyclo[4.2.0]octane-2,8-dione (2).16... 

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... 

Rhodium- and copper-catalysed cyclopropanation of 8-oxabicyclo[3.2.1]octane by diazocarbonyl compounds was achieved in poor to moderate yields. Ring opening of the cyclopropane (40) upon treatment with Sml2 offered a desymmetrization of the original bicycle. 

A very intriguing system 31 with donor-acceptor substitution pattern can be obtained by an intramolecular cyclopropanation 22). The tricyclic product 31 permits several ring cleavage reactions (Scheme 3), some of which are not known for less strained cyclopropanes. All methods lead to oxabicyclo[2.2.2]octane derivatives. Thus, hydro-genolysis proceeds under relatively mild conditions breaking the bond between the donor and the acceptor substituted carbons exclusively. 

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 conformation and the ring strain involved in bicyclo [3.3.0] octanes has been discussed by Armarego102). The cis-fused isomers are more stable than the trans ones. Therefore, trans-3-oxabicyclo [3.3.0] octane polymerizes but ds does not30). 

Bridged ethers incorporating stereocontrolled placement of functionality can be prepared by SnCU-induced cyclization of 3,4-epoxy alcohols. A reaction sequence with a ring contraction and tandem cyclization enables the construction, from unfunctionalized alkenes or arenes, of the 8-oxabicyclo[3.2.1]octane system with one or two additional fused rings (Eq. 51) [84]. 

As mentioned above, we synthesized the novel ortho ester 12 with an oxabicyclo [2.2.2]octane skeleton. However, this compound was not stable. The facile opening of the ether ring produced the corresponding hydroxy ester 19 (Scheme 5). Therefore, we sought to synthesize a stable basic skeleton 20. In the course of these studies, we developed new synthetic methods for an oxabicyclo[2.2.2]octane skeleton 20 and an oxabicyclo[2.2.1]heptane skeleton 21 (Fig. 7). 

The /9-fragmentation of alkoxyl radicals generated from oxabicyclic hemiacetals of the [w.m.O] type is an attractive method for the synthesis of medium-sized and macrolactones by ring expansion reactions (Eq. 7 [36] and Eq. 8 [37], Scheme 3). Moreover, spirolactones can be prepared by fragmentation of other types of oxabicyclic hemiacetals such as 2-oxabicyclo[2.2.2]octan-l-ol and 6-oxabicyclo[3.2.1j-octan-5-ol (Eqs. 9, 10) [36b]. 

Application of RCM to acrylates derived from terpene aldehydes containing a remote double bond yielded the 6-substituted dihydropyran-2-ones <01TL6069> and oxabicyclo-[3.2.1]octane undergoes an efficient ring-opening cross-metathesis with electron-rich alkenes to give unsymmetrically 2,6-disubstituted tetrahydropyran-4-ones <01OL4275>. 

When a substrate with a diazo functionality at the 5-position to the carbonyl group, e.g. 44, is reacted with an appropriate transition metal catalyst, a cyclic six-membered ring carbonyl ylide 45 is formed as a transient species via transannular cyclization onto the 5-positioned carbonyl oxygen. These transient species 45 readily engage in inter- or intramolecular [3+2]-cycloadditions with a variety of dipolarophiles to furnish oxabicyclo[3.2.1]-octan-2-ones 46 (Scheme 13). 

The synthesis of the oxabicyclo[3.2.1]octan-2-one ring system was successfully accompUshed via the 1,3-dipolar cycloaddition of 6-membered ring carbonyl yUdes. hi a reactivity profile similar to that of the five-membered carbonyl yhdes (see Schemes 14,15), the carbonyl ylide derived from 1-diazo-... 

Synthesis of endo spiro-oxabicyclo[3.2.l]octan-2-ones 85 has been reported based on the reaction of the six-membered ring carbonyl ylide generated from the diazo ketone 80 with cr-methylene ketones (Scheme 25) [88]. Importantly, the reverse stereoselectivity was observed between the reactions involving five-membered ring carbonyl ylide intermediates and 66, which led to exo spiro compounds (see Scheme 19). 

The oxabicyclo[3.2.1]octan-2-one ring systems form a core skeleton of many naturally existing molecules. In an approach towards guaianolide sesquiterpenes, their hydroazulenic framework has been constructed through a rhodium(II)-catalyzed reaction [82] of the a-diazo ketone 106 with DMAD to afford the oxatricyclic system 107, which forms the skeleton of ambrosic acid 108 (Scheme 33). 

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