Diastereoselective Singlet Oxygen Ene Reaction (Schenck Reaction) and Diastereoselective Epoxidations of Heteroatom-Substituted Acyclic Chiral Olefins:  A Mechanistic Comparison

Abstract

The directing propensity of allylic and homoallylic heteroatom substituents on the diastereoselective singlet oxygen ene reaction (Schenck reaction) of acyclic, chiral olefins has been investigated. These extensive stereochemical results offer evidence for our proposed mechanism of the diastereoselective singlet oxygen ene reaction. Thus, provided a substrate possesses sufficient 1,3-allylic strain to populate preferentially the appropriate conformation, the photooxygenation is directed threo-selectively by intramolecular hydrogen bonding in the threo-A exciplex of allylic alcohols, while electron-accepting or bulky substituents result in the erythro-configurated products. A detailed comparison of the diastereoselectivities for the singlet oxygen ene reaction with those of the epoxidation by m-chlorobenzoic acid (mCPBA) and dioxirane of several judiciously chosen substrates showed that both oxygen transfer processes are influenced similarly by allylic and homoallylic substituents. Thus, it is shown that the acyclic, allylic alcohol 1a is epoxidized highly threo-selectively by methyl(trifluoromethyl)dioxirane due to hydrogen bonding in the transition state and that bulky and/or electron-accepting substituents direct all three oxidants erythro-selectively. These pronounced steering effects on the diastereoselectivity of oxygen transfer processes (photooxygenation and epoxidation) should be valuable for the rational design of stereocontrolled oxyfunctionalizations by 1O2, mCPBA, and dioxiranes.

Recent Mechanistic Insights in the Singlet Oxygen Ene Reaction

“…In particular, the 1 O 2 ene reaction of chiral allylic alcohols, 121 amines and ammonium salts 122 displayed a high threo selectivity in nonpolar solvents. On the other hand, electron-accepting X substituents (e.g., SO 2 Ph, CO 2 Et, CO 2 H, Cl and Br) 123 promoted highly regioselective 1 O 2 ene reactions in moderate to good erythro stereocontrol in non-polar solvents.…”

Regio-, Diastereo-, and Chemoselectivities in the Dioxirane Oxidation of Acyclic and Cyclic Allylic Alcohols by Methyl(trifluoromethyl)dioxirane (TFD): A Comparison with Dimethyldioxirane

“…[8] by TFD at the 6,7 position, but the regioselectivity decreases (entries 1Ϫ3) from that in the most polar MeOH/ In competition with such hydroxy-directed diastereoselective epoxidations, also allylic oxidation to the TFA (9:1) to the least polar CCl 4 /TFA (9:1) medium (TFA stands for 1,1,1-trifluoroacetone). In contrast, the geraniol corresponding enone has been observed for a variety of allylic alcohols in the DMD oxidations.…”

Selective Formation of Allylic HydroperoxidesviaSinglet OxygeneneReaction

“…The same electrostatic repulsion seems to be operative for other acyclic substrates such as allylic halides, sulphones, carboxylic acids and esters presented in Scheme 38 4,93 . In contrast to the stabilizing effect of the allylic alcohols and amines, electrostatic repulsion disfavours the approach of singlet oxygen from the π face bearing the previously mentioned electron-withdrawing functional groups.…”

“…Recently, however, Adam and coworkers reported a high chiral-auxiliary-controlled diastereoselectivity in the singlet oxygen ene reaction in CDCl 3 of the optically active oxazolidines 93 presented in Scheme 40. The observed selectivity was attributed to electronic attraction through hydrogen bonding between the NH group of the urea functionality and the attacking singlet oxygen.…”