Cyclooctene oxide

Treatment of ris-cyclooctene oxide (15) with lithium diethylamide in ether at reflux gave endo-ris-bicyclo[3.3.0]octan-2-ol (16) in 70% yield. Under identical conditions, trons-cyclooctene oxide (17) gave exo-as-bicyclo[3.3.0]octan-2-ol (18) in 55-60% yield (Scheme 5.6) [7]. In each case, the reaction is completely stereospe-cific, with neither of the epimeric alcohols being observed, which suggests that the reactions proceed through insertion of a carbenoid (rather than the same a-li-... 

Using substituted a-methylene-(3-acetoxy ketones 2-494 with R = Me, Et, iPr, Ph and LiOtBu as base, the yields of the cycloheptene oxide 2-498 could be greatly enhanced to up to 77 %, as in the case of2-498b. In addition, cyclooctene oxides can be prepared (though in lower yield and stereoselectivity) starting from a six-membered oxosulfonium ylide. 

A systematic study has confirmed the low activity of EHs toward cycloalkene oxides (1,2-epoxycycloalkanes, 10.123) [184], In the presence of mouse liver microsomal EH, activity was very low for cyclopentene oxide and cyclohexene oxide (10.123, n = 1 and 2, respectively), highest for cyclo-heptene oxide (10.123, n = 3), and decreased sharply for cyclooctene oxide (10.123, n = 4) and higher homologues. Mouse liver cytosolic EH showed a different structure-activity relationship in that the highest activity involved cyclodecene oxide (10.123, n = 6). With the exception of cyclohexene oxide, which exhibited an IC50 value toward microsomal EH in the p.M range, cycloalkene oxides were also very weak inhibitors of both microsomal and cytosolic EH. 

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. 

The desymmetrization works also well with higher substituted meio-epoxides such as ewdo-norbornene oxide (130) , cis-5,6- and 4,7-difunctionalized cyclooctene oxides 132 and 134, giving the alcohols 131, 133 and 135, respectively but for the diastereomer 136, the rearrangement to form the allylic alcohol 138 beside 137 cannot be completely suppressed (equation 29 best results are given). ... 

Astonishingly enough, enantioenriched lithiated cyclooctene oxides 142, originating from (—)-sparteine-mediated lithiation of 124 by i-BuLi/(—)-sparteine (11), could be trapped by external electrophiles, resulting in substituted epoxides 143 (equation 31) ° . Again, the use of i-PrLi furnished better enantioselectivities (approx. 90 10). Lithiated epoxides, derived from tetrahydrofurans and A-Boc-pyrrolidines, undergo an interesting elimination reaction . ... 

The RLi homochiral ligand complexes are seldom used for the base-promoted isomerization of oxiranes into allylic alcohols because their poor chemoselectivity lead to complex mixtures of products. As examples, the treatment of cyclohexene oxide by a 1 1 i-BuLi/(—)-sparteine mixture in ether at low temperature provides a mixture of three different products arising respectively from -deprotonation (75), a-deprotonation (76) and nucleophilic addition (77) (Scheme 32) . When exposed to similar conditions, the disubstituted cyclooctene oxide 78 affords a nearly 1 1 mixture of a- and -deprotonation products (79 and 80) with moderate ee (Scheme 32, entry 1). Further studies have demonstrated that the a//3 ratio depends strongly on the type of ligand used (Scheme 32, entry 1 vs. entry 2) . ... 

In the case of cyclooctene oxide 24, the nature of the base used has a direct influence on the competition between a- and /3-deprotonation, as already discussed in Section 11. 

Several efficient procedures for alkene epoxidation using Oxone were reported, such as Oxone/aqueous NaOH, Oxone/acetone, Oxone/water , Oxone/PTC/benzene/ aqueous buffer solution or Oxone/2-butanone system. Thus, sorbic acid can be regioselectively oxidized using Oxone/aqueous NaOH to 4,5-epoxy-2-hexenoic acid in 84% yield. Similarly, cyclooctene is oxidized to cyclooctene oxide in 81% yield, just by stirring it with Oxone in water . 1-Dodecene is epoxidized in good yield by Oxone/PTC in benzene aqueous buffer solution. It is otherwise difficult to epoxidize 1-dodecene by other oxidizing reagents. ... 

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... 

Cope and co-workers3 2- conducted elegant studies of the effect of strong bases like lithium diethylamide and phenyllithiutn on the cm- andfrotur isoroem of cyclooctene oxide (Eqs. 497 and 498). Complex... 

Cyclohexylmethane, ml 94 Cyclohexylmethyl bromide, b306 Cyclooctene oxide, e7a Cyclopentanepropanoic acid, c363 Cyclopentene oxide, e37... 

Denmark et al. employed the chiral phosphoramide 74 (Scheme 13.37) as nucleophilic activator [75]. As summarized in Scheme 13.37, the best enantiomeric excess was observed for cis-stilbene oxide (87%). The study revealed that enantioselectivity was highly dependent on the ring size (cyclohexene oxide cyclopentene oxide > cyclooctene oxide). 

EPOXIDATION OF OLEFINS BY HYDROGEN PEROXIDE-ACETONITRILE cw-CYCLOOCTENE OXIDE... 

This epoxide has been found to be particularly useful in the laboratory in the large-scale preparation of frarty-cyclooctene using the procedure of Whitham.14 trans-Cyclooctane- 1,2-diol is obtained from cis-cyclooctene oxide on treatment with sodium acetate in acetic acid and alkaline hydrolysis of the intermediate trans-2-acetoxycyclooctanol. The trans diol is converted to its benzal-dehyde acetal, which on treatment with butyllithium affords trans-cyclooctene in a stereospecific manner. 

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