Domino Michael/cyclisation reactions

These reaction conditions were also applied to the domino Michael/cyclisation reactions of other nucleophiles, such as 4-hydroxy-6-methyl-2-pyrone 43, 4-hydroxycoumarin 44, and 3-hydroxyperinaphthenone 45, as shown in Scheme l. hlF By reaction with variously substituted l-(alk-2-enoyl)-4-bromo-3,5-dimethylpyrazoles, these compounds afforded the corresponding chiral domino products 46a-c, 46d-h, and 47, respectively. These products arose from domino Michael/cyclisation reactions and were obtained in moderate to good yields and with good to high enantioselectivities of up to 98% ee. 

Scheme 2.35 Domino Michael/cyclisation reaction of dimedone with l-(2-cro-tonoyl)-3,5-dimethylpyrazoles catalysed by an in situ generated (i ,i )-DBFOX-Ph nickel catalyst.

Scheme 2.39 Domino Michael/cyclisation reaction of cyclic 1,3-dicarbonyl compounds with p,y-unsaturated a-keto esters catalysed by an in situ generated iV,iV -dioxide nickel catalyst.

Scheme 4.5 Domino Michael/cyclisation reaction of dimedone with l-(2-crotonoyl)-3,5-dimethylpyrazoles.

Scheme 4.7 Domino Michael/cyclisation reactions of enols with l-(alk-2-enoyl)-4-bromo-3,5-dimethylpyrazoles.

Scheme 2.3 Domino Michael-cyclisation reactions catalysed by a combination of a chiral cinchona alkaloid-derived primary amine and a chiral phosphoric acid.

Cooperative catalysis using cinchona alkaloid derivatives in combination with metals such as silver have also been widely developed. On the basis of this concept, Escolano et al. have disclosed an enantioselective domino Michael-cyclisation reaction. This formal [3 + 2] cycloaddition occurred between isocyanoacetates and enones in the presence of a combination of a chiral hifunctional cinchona alkaloid, such as cupreine, and AgNOs to provide the corresponding chiral 2,3-dihydropyrroles in low to high yields and... 

Domino Michael-cyclisation reaction catalysed by chiral cinchona alkaloid catalysis and silver catalysis. 

Scheme 1.35 Silylated biphenylprolinol-catalysed domino Michael addition-cyclisation reactions.

Scheme 2.22 Three-component domino Michael-Mannich-cyclisation reaction catalysed by a combination of chiral diphenylprolinol triethylsilyl ether and a chiral thiourea.

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

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