Hydroxy-directed regio- and diastereoselective ene reaction of singlet oxygen with chiral allylic alcohols

Article abstract of DOI:10.1021/ja00065a013

The photooxygenation of chiral allylic alcohols 1a, (Z)-1f-k, ethers 1b-d, and acetate 1e gave the corresponding hydroperoxy homoallylic alcohols and derivatives 2 through the ene reaction with singlet oxygen. While the reaction of the acetate le proceeded eryrthro-diastereoselectively as a result of the classical cis effect, for the allylic alcohols la and (Z)-1f-k, in which an alkyl group is located cis to the hydroxy-bearing substituent, high threo selectivity was observed. This finding is explained in terms of coordination of the nucleophilic hydroxy functionality of the stereogenic center with the incoming electrophilic singlet oxygen enophile. The stereodifferentiation is a consequence of the preferred conformation of the allylic alcohol for oxygen transfer, which is mainly determined by 1,3-allylic strain, while the influence of 1,2-allylic strain is small. A similar sensitivity toward both types of allylic strain is observed in epoxidations with m-CPBA, for which stereocontrol by cooperation of hydroxy-coordination and allylic strain is established. These similarities were convincingly demonstrated for the chiral allylic alcohol (Z)-1g as a novel stereochemical probe. Moreover, from these results it can be concluded that the optimal C=C-C-O dihedral angle of the allylic alcohol in the transition state for the singlet oxygen ene reaction lies between 90° and 130°. In addition to the threo selectivity with which the hydroperoxy moiety is introduced, the newly formed allylic double bond in the hydroperoxide is exclusively formed in the E configuration, as exemplified for the chiral allylic alcohol (Z)-1k; again, allylic strain in the ¹O₂ ene reaction is responsible.