Cycloaddition Reactions

Abstract

This chapter deals with enantioselective organocatalytic cycloaddition reactions. Several cinchona alkaloids have been recently demonstrated as efficient chiral organocatalysts for enantioselective Diels−Alder reactions. Thus, excellent results were obtained for the Diels−Alder reaction of 3-vinylindoles with maleimides catalysed by a chiral bifunctional thiourea derived from hydroquinine, leading almost exclusively to the corresponding endo-carbazoles in high enantioselectivities. In addition, a diarylprolinol silyl ether salt has proved to be an efficient organocatalyst for the enantioselective Diels−Alder reaction of cyclopentadiene with α?β-unsaturated aldehydes performed in water. Under solvent-free conditions, the cycloadducts were obtained in good exo-selectivities combined with excellent enantioselectivities. Some chiral organocatalysts were also successfully applied to promote asymmetric inverse-electron-demand hetero-Diels−Alder reactions. As an example, the aza-Diels−Alder reaction of N-sulfonyl-1-aza-1,3-butadienes with aldehydes yielded the corresponding hemiaminals in excellent enantioselectivities in the presence of chiral α?α-diphenylprolinol trimethylsilyl ether as organocatalyst. In the same area, the oxa-Diels−Alder reaction of α?β-unsaturated trifluoromethyl ketones with aldehydes performed in the presence of this organocatalyst provided the corresponding cyclic adducts in both high anti-diastereo- and enantioselectivities. Other successful enantioselective organocatalytic cycloadditions were developed, such as a three-component 1,3-dipolar cycloaddition between aldehydes, amino esters, and dipolarophiles catalysed by a new biphosphoric acid derived from (R,R)-linked BINOL, furnishing multiply substituted pyrrolidines in excellent enantioselectivities. In addition, a new class of chiral bifunctional thiourea catalysts derived from trans-2-amino-1-(diphenylphosphino)cyclohexane was applied to a highly enantioselective synthesis of a wide range of 2-aryl-2,5-dihydropyrrole derivatives on the basis of a [3+2] cycloaddition between an N-phosphinoyl imine and an allene.