Allylic hydroperoxides synthesis

AUyl transfer reactions, 73, 1 Allylic alcohols, synthesis from epoxides, 29, 3 by Wittig rearrangement, 46, 2 Allylic and benzylic carbanions, heteroatom-substituted, 27, 1 Allylic hydroperoxides, in... 

The allylic oxidation of alkenes by O2 involves an ene reaction, and proceeds with rearrangement s as in Scheme 4. The intermediate allylic hydroperoxide (5) can be reduced to yield an allylic alcohol (6), or be treated with base to give an unsaturated carbonyl conqiound (7). The reaction works best on tri- or tetra-substituted alkenes, and the relative preference for attack is Me - CH2 CH. The O2 allylic oxidation has been used in the synthesis of a large number of natural products, including some naturally occurring allylic hydroperoxides. It is possible that O2 reactions of this type are involved in biosynAetic processes. 

The classical method for the synthesis of epoxy alcohols is the epoxidation of allylic alcohols, the latter accessible by reduction of allylic hydroperoxides or other more traditional methods. One of the most valuable reactions for preparative purposes is the Sharpless method82 83, in which, for chiral allylic alcohols, the epoxy alcohols are produced diastereoselectively and, in the presence of chiral ligands, also in high enantioselectivity (see Section D.4.5.1.). 

Singlet Oxygen.—Singlet oxygen reacts with dienes to give e do-peroxides and with alkenes to give allylic hydroperoxides or dioxetans. " The mechanism of the latter reaction is still under investigation. The use of these reactions in natural products synthesis has been comprehensively reviewed, "— " and attention will be concentrated on recent work. 

Schmid and Hofheinz described an important application of this reaction to the total synthesis of the antimalarial drug artemisinin. The key step in the (-)-isopulegol-based synthesis is the ene-reaction of singlet oxygen with an enol ether (Scheme 12). This reaction leads to an allylic hydroperoxide 20 when the reaction is performed in the nonpolar solvent, CHjClj. The use of the more polar, protic methanol inverts the regioselectivity, and the a-hydroperoxy acetal 21 is formed (presumably by trapping of an intermediary 1,4-zwitterion), which is cycHzed to the target molecule 22 by acid catalysis. 

Two carbonyl fragments could also be formed on acid-catalyzed hydrolysis of the aUyhc hydroperoxides that mostly proceeds through Hock-type fragmentation. AUyHc alcohols obtained by reduction of the corresponding allylic hydroperoxides are versatile building blocks with diverse synthetic utility they could also be either regioselectively dehydrated to l,3-dienes or oxidized to a,P-unsaturated ketones. The ene-reaction was also utilized in the synthesis of some natural products and diastereoselective allene derivatives. ... 

Adam, W. and Klug, R, P-Stannyl allylic alcohols through photooxygenation (Schenck reaction) of vinylstannanes and reduction of the resulting aUyhc hydroperoxides synthesis and selected transformations,/. Org. Chem., 59, 2695, 1994. 

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