Cycloadditions with Carbodienophiles

Cycloaddition reactions of (E)-l-acetoxybutadiene (18a) and (E)-l-methoxy-butadiene (18b) with the acrylic and crotonic dienophiles 19 were studied under high pressure conditions [9] (Table 5.1). Whereas the reactions of 18a with acrylic dienophiles regioselectively and stereoselectively afforded only ortho-enJo-adducts 20 in fair to good yields, those with crotonic dienophiles did not work. Similar results were obtained in the reactions with diene 18b. The loss of reactivity of the crotonic dienophiles has been ascribed to the combination of steric and electronic effects due to the methyl group at the )S-carbon of the olefinic double bond. 

Diels-Alder reaction of 2-cyclohexen-l-one (37) with diene 38 mainly afforded the exo adduct 39, the key intermediate in the synthesis of the bottom half of chlorothricolide [14] (Equation 5.4). 

Similarly, cycloaddition of the cyclohexenone-like dienophile 40 with 2-tri-methylsilyloxy-1,3-butadiene (41) allowed [7] the regio- and stereoselective synthesis of tetracyclic compound 42, in high yield (Equation 5.5). 

Quinone-mono-ketals 46 and 47 are also low reactive dienophiles and are sensitive to Lewis-acid catalysts. The use of high pressure overcomes this limitation [17]. As shown in Equation 5.7, cycloadditions with a variety of substituted 1,3-butadienes 48 occur regioselectively and c fo-diastereoselectively in reasonable to good yields. This approach provides access to a variety of annulated benzenes and naphthalenes after aromatization of adducts 49. 

The different ratios of 52/53 produced by cycloadditions performed at atmospheric and high pressure, and the forma tion of the unusual trans adducts 53, have been explained by the facts that (i) Diels-Alder reactions under atmospheric pressure are thermodynamically controlled, and (ii) the anti-endo adducts 52 are converted into the short-lived syn-endo adducts 54 which tautomerize (via a dienol or its aluminum complexes) to 53. The formation of trans compounds 53 by induced post-cycloaddition isomerization makes the method more flexible and therefore more useful in organic synthesis. 

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Vinylpyrazoles react with NPMI to afford functionalized indazole derivatives through [4 + 2]-cycloaddition reactions in a way similar to that of other carbodienophiles such as acetylenic esters. So with 4-vinylpyrazole derivatives, mixtures of 1 1 and 1 2 cycloadducts (formed via an ene reaction) were obtained (86T6683 89MI113), whereas with the 5-isomer only the 1 1 cycloadduct was isolated (Scheme 7) [90JCS(P1 )2749]. 

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