Singlet oxygen cycloaddition with dienes

Recently the solvent effect on the [4+2] cycloaddition of singlet oxygen to cyclic dienes has been subjected to a multiparameter analysis. A pre-equilibrium with charge-transfer character is involved, which is affected by the solvent through dipolarity-polarisability (n ) and solvophobic interactions ( Sjf and Another multiparameter analysis has been published by Gajewski, demonstrating the... 

Singlet oxygen undergoes [4 + 2] cycloaddition with dienes. 

While both hydrogenation and epoxidation reactions of (7) (and substituted forms) occur on the oxepin valence tautomer, cycloaddition reactions proceed more readily on the arene oxide form (where the diene is closer to planarity). Thus the dienophiles DM AD and maleic anhydride (MA) readily yielded [4 + 2] cycloadducts with (7) as shown in Scheme 22 (67AG(E)385). A similar type of singlet oxygen cycloaddition reaction gave an unstable endoperoxide (106) which upon heating yielded trans-benzene trioxide quantitatively (equation 14). (75JOC3743). 

The synthesis of fenozan BO-7 4 involves two key steps, the first of which employs a 4 + 2 cycloaddition of singlet oxygen to the diene 83a122-20 123. This provides the endoper-oxide 83b that can be transformed into the target cis-fused 1,2,4-trioxane by treatment with the Lewis acid, TMSOTf, in the presence of a carbonyl compound. The reaction proceeds by Lewis acid promoted heterolysis of the C—O bond to give an intermediate peroxy allyl cation 83c that is captured by the carbonyl compound (in this case, cyclopen-tanone) to give the product (Scheme 30). A number of different carbonyls have been used in this reaction along with a number of different endoperoxide templates and detailed SAR have been developed (Scheme 30). 

A (4 + 2) cycloaddition can take place between singlet oxygen and conjugated dienes that are free (or constrained) to adopt an s>c/s conformation (2.93). When such a reaction occurs with an aryl-conjugated alkene (2.94), the first-formed cycloadduct is itself a conjugated triene, and the overall reaction produces a bis-(4 + 2) adduct. 

On a first, very broad, approximation singlet oxygen behaves somehow like ethylene. Three types of reactions of 102 are usually observed and have been utilized in organic synthesis 606 608) a) the Diels-Alder like cycloaddition to dienes (6.1) b) the ene reaction with olefins (6.2) and c) cycloaddition to activated double bonds (6.3). 

Acetylenic ethers 7 can be hydrozirconated, and subsequent iododezirconation leads to (fc)-iodo enol ethers 8 (Scheme 4.4) [18], These species undergo efficient Sonogashira couplings to give (E)-enynes, which are ultimately converted to stereodefined dienol ethers. These dienes have proven useful in studies of diastereoselective cycloaddition reactions with singlet oxygen, where R in 8 is a nonracemic auxiliary (e. g., menthyl) (Procedure 3, p. 140). 

Due to the formal analogy to the classical Diels-Alder reaction, the mechanism of cyclic peroxide formation through cycloadditions of 1,3-dienes with O2 was considered for a long time to involve a concerted suprafacial [4 4- 2]-cycloaddition of a super-dienophile, namely a singlet oxygen to 1,3-dienic system In such a case, the concerted or almost concerted cycloaddition must be c -stereospecific and the stereochemical properties of the diene must be reflected in the three-dimensional structure of cyclic peroxide according to well-defined rules. Indeed, it was found in early stereochemical... 

Singlet oxygen reacts through the [4- -2]-cycloaddition mode with the sterically hindered and non-planar 1,3-diene system in l,l -dimenthene (493) to afford the cis-endoperoxide 494, albeit in moderate yield (Scheme 135) ". Cycloaddition of O2 to more planar bis(dialine) (495) proceeds smoothly leading predominantly to the trans-endoperoxide trans-496 (70%), while cis-496, which would be expected to derive from a concerted process, constitutes the minor (15%) product (Scheme 136) . 

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