Stereochemistry in the Ene Reactions of Singlet Oxygen and Triazolinediones with Allylic Alcohols. A Mechanistic Comparison

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The ene reaction of singlet oxygen with (Z)-4-methylpent-3-en-2-ol-2,5,5,5-d4 (1-OH-d4) in nonpolar solvents exhibits a 90% threo diastereoselectivity in the adduct derived from the major syn perepoxide intermediate, but also a moderate threo diastereoselectivity in the adduct derived from the minor anti perepoxide. Photooxygenation of 2,4-dimethylpent-3-en-2-ol (2) exhibits a significant solvent dependence in the syn/anti methyl stereoselectivity, with nonpolar solvents promoting syn methyl reactivity, while polar solvents promote anti methyl reactivity. These results are in agreement with a steering effect between hydroxyl and singlet oxygen in the rate-determining step of the reaction. N-Phenyltriazolinedione addition to the chiral allylic alcohol 4-methylpent-3-en-2-ol (1-OH) is highly threo diastereoselective in nonpolar solvents, with a solvent dependent variation in the threo/erythro ene products. On the other hand, the nonfunctionalized chiral alkene 2,4-dimethyl-2-hexene (1-Et) exhibits poor diastereoselectivity. Reaction of PTAD with 1-OH-d4 in nonpolar solvents, exhibits a significant threo diastereoselectivity from the syn aziridinium imide intermediate, and a moderate threo diastereoselectivity from the anti intermediate. These results are consonant with a steering effect between the hydroxyl and the electrophile, as proposed in the case of singlet oxygen addition to allylic alcohols 1-OH and 2. In contrast to the analogous 1O2 ene reaction, a solvent independent ratio syn/anti ∼ 50/50 was found in the addition of MTAD to 2. The intermolecular kinetic isotope effect in the reaction of 2 with MTAD (kH/kD = 1.15 ± 0.02), is consistent with formation of the intermediate in fast step, indicative that the steering effect during the formation of aziridium imide is not important in the reaction kinetics. This energetic profile is in contrast to triazolinedione addition to the secondary allylic alcohol 1-OH, where the high threo selectivity and the slight inverse kinetic isotope effect of kH/kD = 0.98 ± 0.02 are consonant with the formation of the intermediate in the rate-determining step. An explanation for the increased reactivity of the syn methyl in the addition of MTAD to 2 (∼50%) is offered.