Stereoselective cycloaddition and epoxidation of enol ethers by alpha-peroxy lactone as a function of steric and stereoelectronic effects

The reaction of mono- and dioxy-substituted olefins 2 with dimethyl alpha-peroxy lactone 1 affords the cycloaddition products 3 and the epoxides 4 with a high degree of stereoretention of the initial olefin configuration. Only for the pyran 2c is the ene product 5c obtained. When the reaction is run in methanol as cosolvent, additionally the trapping products 6 are observed. The S(N)2 reaction is found to be highly regioselective in all cases, as displayed by the cycloadducts 3 and the trapping products 6. The preferred reaction mode has been found to be sensitive to steric effects. The product distribution is rationalized in terms of the diastereomeric 1,4-zwitterionic epoxonium intermediates syn- and anti-C, which are proposed to arise from a side-differentiated S(N)2 attack of the enol ether double bond on the peroxide bond of the alpha-peroxy lactone 1 through a perpendicular spiro-configurated transition state geometry. When the alpha-peroxy lactone 1 approaches the enol ether 2 from the oxy-substituted side, the syn-C epoxonium intermediate is formed, which leads to the epoxide 4 after release of the corresponding alpha-lactone. The latter oligomerizes to the polyester 8 or is trapped in methanol as the alpha-methoxy acid 9. On the contrary, the anti-C epoxonium intermediate results by approach of the alpha-peroxy lactone 1 from the non-oxy-substituted side of the enol ether 2, but the electronic repulsion between the lone pairs of the epoxonium and enol ether oxygens leads by ring opening of the epoxonium species to the coiled 1,6-zwitterion (U conformation). The latter is too short-lived for stereorandomization and closes to the cycloadducts 3 under high retention of the initial enol ether configuration, but is sufficiently long-lived to be trapped in methanol stereoselectively in form of the adducts 6. These unprecedented results in the peroxide-olefin reaction are contrasted with the previously reported alpha-peroxy lactone 1 oxidation of alkenes. While the enol ethers 2 lead to the cycloadducts 3 with a high degree of stereoretention and the alkenes lead to extensive loss of the initial olefin geometry, for both trapping by methanol in form of the adducts 6 takes place, again with high stereoselectivity for the enol ethers but not for the alkenes. This mechanistic dichotomy requires different intermediates, namely, the epoxonium species C for the enol ethers and the stretched 1,6-dipole (W conformation) A for the alkenes, which both lead to the cycloadducts 3, the former by way of the coiled 1,6-dipole (U conformation) D. For the enol ethers the epoxonium intermediate C is the precursor to the epoxide, while for the alkenes an independent concerted ''butterfly'' transition state geometry B applies in the epoxidation.