Cyclooctene oxides, transannular

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

Cleavage of epoxides (6, 16-17 8, 10-12). Cleavage of epoxides catalyzed by Woelm neutral alumina is particularly useful in the case of medium-ring epoxides, which are generally rather unreactive and which are liable to undergo transannular reactions. For example, rw-cyclooctene oxide supported on neutral alumina is converted to rran.r-2-acetoxycyclooctanol in 78% yield by reaction with acetic acid at... 

Asami and coworkers also investigated the deprotonation of cyclooctene oxide 97, which is known to undergo both a-deprotonation to yield transannular products and / -deprotonation to yield allylic alcohols 98 upon reaction with lithium amides. Using his catalytic system Asami and coworkers obtained the allylic alcohol in 27% yield and 54% ee of (,S )-98 (Scheme 68c). (Z)-4-Octene oxide 99 was deprotonated yielding the allylic alcohol 100 in 54% yield and 60% ee of the (5)-enantiomer (Scheme 68d)110. 

Transannular hydride shifts, first detected by Cope and coworkers in solvolyses of cyclooctene oxide, have subsequently been found in a number of related systems, e.g. cyclooctadiene monoepoxides, CA o-bicyclo[3.3.1 ]non-2-ene epoxide and l-oxaspiro[2.6]nonane. In general these reactions do not involve skeletal rearrangements, and they will not be discussed in detail. 

The effect of different substitution on this transannular rearrangement was further studied on a range of disubstituted cyclooctene oxides. cis-4,7-Di(t-butyldimethylsilyloxy)-cyclooctene oxide 80 yielded a mixture of bicyclic alcohol 81, and alkene 82 arising from reductive alkylation [Eq. (28)] [61,62]. 

Enantioselective desymetrization by a-deprotonation/tran-sannular C—H insertion of cyclooctene oxide (i.e., 173) was reported by Hodgson and co-workers for synthesis of bicycle[3.3.0] octanes, intermediates that are useful for pol-yquinane synthesis. The best yields and enantioselec-tivities of 175 were obtained when 173 was treated with j-PrLi and (—)-a-isosparteine (Scheme 20.42). Application of this reaction in natural product synthesis is yet to be reported. The same research group also reported expanding the scope of the reaction to synthesis of indolizidine 177 by a similar transannular reaction of 176. ... 

In addition to asymmetric deprotonation. Cope observed that cyclic epoxides in the presence of base give rise to products derived from transannular reactions [110], Boeckman carried out a study of oxiranes fused to medium-size rings and noted that the more commonly observed deprotonation of oxiranes can be suppressed at low temperature, permitting the formation of bi-cyclic structures [118]. In such cases, a-lithiation of an epoxide followed by 1,1-elimination generates a carbene that participates in a subsequent CH-insertion process (cf. 131). An enantioselective version of this reaction was investigated by Hodgson (Scheme 9.15) [119]. Thus, in the presence of sparteine (130), treatment of cyclooctene oxide 129 with i-PrLi affords bicyclic alcohol 132 in 84% ee. 

Not only allylic alcohols but also homoallylic alcohols can be epoxi-dized. A peculiar transannular oxidation takes place when 1-methyl-4-cycloocten-l-ol is treated with the Fieser reagent, [CrOj-(CH3C0>20-CH3C00H], or with pyridinium chlorochromate. Two dia-stereomeric keto oxides are formed in different ratios (equation 281) [535],... 

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