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

Abstract

The photooxygenation of chiral allylic alcohols la, (Z)-lf-k, ethers lb-d, and acetate le gave the corresponding hydroperoxy homoallylic alcohols and derivatives 2 through the ene reaction with singlet oxygen. While the reaction of the acetate le proceeded erytAro-diastereoselectively as a result of the classical cis effect, for the allylic alcohols la and (Z)-lf-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

A Mechanistic Spectrum of Chemical Reactions

“…Hydrogen bonding to the pendant (tailing) oxygen (Scheme 21) in the perepoxide quasi-intermediates controls the facial/diastereoselectivty of the ene reactions of 42 S. Inagaki singlet oxygen with allylic alcohols [106,107] and amines [108,109]. The allylic alcohol exhibits a striking diastereoselectivity for the threo (S*S*) b-hydroxy allylic hydroperoxide while its acylated derivative exhibits a modest erythro (S*R*) diastereoselectivity.…”

Selective Formation of Allylic HydroperoxidesviaSinglet OxygeneneReaction

“…The high diastereoselectivity observed in the photooxygenation of certain chiral allylic alcohols 45,46 , amines 47,48 and derivatives, which will be analysed in Section III.B.1, was rationalized in terms of hydroxyl or amino group coordination with the incoming oxygen. The synergy of oxygen-hydroxyl coordination as well as the 1,3-allylic strain provides, in non-polar solvents, high selectivity for the threo allylic hydroperoxides.…”

“…Singlet oxygen affords a variety of regio and diastereoselective reactions with chiral allylic alcohols 45,46,140 , amines 47,48,193 (e.g. substrate 161, Scheme 58) and chiral cyclohexadienes 91, 92 that are useful for synthetic transformations.…”

Type II photooxygenation in polymer matrices for the synthesis of new antimalarial peroxides

“…Thus, stereoelectronic control is decisive in all cases where an orthogonal alignment of the reactive CH bond (involved in the hydrogen transfer step) is accompanied by a face directing effect. Remarkable steering effects of the diastereoselectivity for the ene reaction were discovered with chiral allylic alcohols (Scheme 6) [58,59]. The hydroxy group is conformationally aligned by 1,3-allylic strain and hydrogen bonding coordinates the incoming enophile with preferential formation of the threo-configured ene product.…”