Epoxides carbene precursors

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

Periplanone B is the most active sex pheromone found in the alimentary tract and excreta of the American cockroach Periplaneta americana. An elegant total synthesis of this germacrane sesquiterpene was achieved by SCHREIBER and SANTINI Cyclodecatrienone 1 is an obvious precursor. One of the oxirane rings arises from epoxidation of the enone CC double bond, the other from [2-1-1]-cycloaddition of a carbene to the carbonyl bond of the enone. Oxidation of the methylene group introduces the additional carbonyl double bond. The CC double bond of the enone results from an elimination of HX in the a-X-substituted cyclodecadienone 2, which, on its part, is feasible by substitution of cyclodecadienone 3. An electrocyclic opening of the cyclobutene ring in 4 provides the 1,3-diene substructure in 3. 

The basics and the synthetic potential of olefin metathesis has been recently presented in a comprehensive handbook and several reviews [58]. Thus, this chapter will be restricted to demonstrate the scope and flexibility of this type of reaction in the total synthesis of a complex natural product skeleton such as epothilone. The first total syntheses of these antitumor-active 16-membered macrolactones were based on a ringclosing metathesis (RCM) strategy (Scheme 11.36) [73]. Grubbs catalyst 143 has been used for the construction of the endocydic 1,2-disubstituted C12-C13 double bond in epothilone C 148 that, after epoxidation, affords epothilone A 150 [74]. In this approach, ruthenium carbene 143 is more efiident than Schrock molybdenum catalyst 142b [75a[. However, the RCM-route to epothilone D 149, the desoxy precursor of epothilone B 151 bearing a trisubstituted C=C bond, requires the molybdenum carbene catalyst 142b attempts to initiate ring-closure with 143 failed [75]. 

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