Michael reaction proline-catalyzed intramolecular

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

Asymmetric Michael Addition. An intramolecular Michael reaction catalyzed by (S)-proline leads to the chiral thiadecalin (9) and thiahydrindan (11) and (12). Enone (8) undergoes cyclization in the presence of (S)-proline to give exclusively the trans isomer (9) (eq 4). The thiahydrindandions (11) and (12) are obtained from (10) as a 1 1 mixture of the cis and trans isomers (eq 5). 

Subsequently, List reported the first organocatalytic intramolecular Michael reaction of multifunctional aldehydes 10. Although this reaction could also be catalyzed by L-proline, both diastereo- and enantioselectivity were low. MacMillan s chiral imidazolidinone 9 gave much better results and the cyclic ketoaldehydes 11 could be obtained efficiently (Scheme 36.3) [8a]. 

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