Ene reactions with singlet oxygen

AUylic alcohols constitute an alternative valuable source for the preparation of S-hydroperoxyalcohols suitable for peroxyacetalization to 1,2,4-trioxanes. A number of 3-alkyl-substituted allyl alcohols undergo a highly regio- and stereoselective ene-reaction with singlet oxygen to generate the corresponding /l-hydroperoxyalcohols. ... 

The phenyl ring of styrene substrates directs a syn selectivity in their ene reactions with singlet oxygen. This effect was demonstrated by the photooxygenation of / ,/ -dimethyl styrene (20). This substrate, apart from the ene product, produces the 1,2-dioxetane and two diastereomeric diendoperoxides as shown in Scheme 9. 

Bis-silyl ketene acetals devoid of -protons undergo a clean silatropic ene reaction with singlet oxygen (see Sections 2.3.2.1,3.ii and 2.3.2.4.3.H) to generate the a-silylperoxy silyl ester quantitatively. Treatment with methanol affords the a-hydroperoxy acid, also quantitatively (Scheme 23). Hytkogenation over platinum reveals the a-hydroxy acid, once again, quantitatively. Despite diis encouragement the substrate limitation is severe. 

Other steroid systems have also been investigated. Methyl groups at the bridgehead position always shield the /3-side and thus promote exclusive a-attack. Additionally, for the triacetoxy derivative 1268, an intermediate in the synthesis of a-ecdysone, and for 3j6-acetoxy-8(14)-cholesten-6-one (14)69, the regioselectivity of the ene reaction with singlet oxygen is high. In both cases only the y-hydroperoxy-a,/J-unsaturated ketone is formed. 

Annulated octahydronaphthalene derivatives with trisubstituted C—C double bonds give clean ene reactions with singlet oxygen. Methyl groups at bridgehead positions influence the diastereoselectivity of these reactions. In two examples by Marco et al. (16)71 and Marshall et al. (18)72, a-attack is preferred. 

A further interesting extension of the allyl alcohol epoxidation reaction is the metal-catalyzed direct hydroxy-epoxidation of alkenes. In such a reaction an ene reaction with singlet oxygen, 02, or Schenk reaction forming an ally lie hydroperoxide is combined with metal-catalyzed intramolecular epoxidation to form epoxy alcohols For example, with 2,5-dimethyl-2,4-hexadiene (83) two different isomers, 84 and 85, were obtained with Ti(OPr-/)4 and VO(acac)2, respectively (equation 16). Similar reactions were also car-... 

Griesbeck, A. G., El-ldreesy, T. T., Adam, W., Krebs, O. Ene-reactions with singlet oxygen. CRC Handbook of Organic Photochemistry and Photobiology (2nd Edition) 2004, 8/1-8/20. 

Details for the use of enesilylation for 1,2-transposition of ketones (8, 289-290) have been published.2 The paper includes the conversion of vinylsilanes to rearranged allylic alcohols. The trimethylsily1xgroup directs the ene reaction with singlet oxygen exclusively to the a-position. A typical reaction is shown in equation... 

The trimethylsilyl group of enol silyl ethers can participate in ene reactions with singlet oxygen (60,61). 

The reliability of the ene reaction with singlet oxygen is attested by the fact that this has been chosen as the first step for the conversion of S-citroneUol 10 into one of the four fragments (12) from which the complex structure 13, which has been proposed for the synthesis of the HIV-active didemnaketal A, has been assembled (Scheme 8.3) [3]. 

Two new isomeric hydroperoxides, 135 and 136, were synthesised by the photochemical oxygenation of 43 and 44, via ene reactions with singlet oxygen (Scheme 5.3). 

In earlier years, radical allyl halogenations and selenium dioxide oxidation were quite popular, although in various ways problematic. Nowadays, catalytic hydroxy-lations or ene-reactions with singlet oxygen are the better accepted alternatives. 

METHOX (22) was synthesized in three steps from the commercially available pinocarvone (47) using the Krohnke annulation (47 + 48 —> 50). Pinocarvone itself, commercially available only in one enantiomeric form, can be readily obtained from the much cheaper oi-pinene (46) via an ene-reaction with singlet oxygen. Since both enantiomers of oi-pinene are commercially available, this procedure can be utilized for the preparation of both enantiomers of METHOX (22) [28b], The Krohnke reagent 48 [52] is readily obtained in one pot via iodination of the corresponding acetophenone (49) in pyridine [28bj. 

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