1.3- Dioxolan-4-ones Michael additions

When Michael additions of chiral enolates to nitroalkenes were studied, it was found that lithium enolates (132) of l,3-dioxolan-4-ones (131), derived from the corresponding a-hydroxy acids, afford the adducts (133) with high diastereoselectivity (Scheme 50).144 Recrystallization leads, in general, to diastereomerically pure products, which in turn can efficiently be converted to homochiral compounds like (134), (135) or (136). A number of other chiral enolates (137M140) were also shown to undergo highly selective additions to nitroalkenes however, product configurations were not determined in these cases. 

Selective and efficient Michael additions of heterocyclic enamines (e.g. indoles, pyrroles, and pyrazoles) to enones can be catalysed by ZrCU (2 mol%).150 Michael addition of a - cy an o k e t e n e -. V,. S - ac et al s (RS)2C=CHCN to enones R CH=CHCOR2 can be promoted by TiCl4.151 Addition of the lithium enolate, generated from (2S,5S)- (g) c -l,3-dioxolan-4-one, which in turn was prepared from (S)-mandelic acid and pival-aldehyde, to several 2-arylidene-1,3-diketones, gives the Michael adducts in good yields and diastereoselectivities.152... 

Soon afterward, various types of carbon [40-44], oxygen [45], and phosphorous [46] Michael donors were successfully employed in the thiourea-catalyzed addition to nitroalkenes. In the presence of the bifunctional epi-9-amino-9-deoxy cinchonine-based thiourea catalyst 79a, the 5-aryl-l,3-dioxolan-4-ones 138 bearing an acidic a-proton derived from mandelic acid derivatives and hexafluoroacetone were identified by Dixon and coworkers as effective pronucleophiles in diastereo- and enantioselective Michael addition reactions to nitrostyrenes 124 [40]. While the diastereoselectivity obtained exceeded 98%, the enantiomeric excess recorded... 

Scheme 4.14 Enantioselective Michael addition of racemic 5-aryl-l,3-dioxolan-4-ones to nitroalkenes.

In 1992, Desmaele utiUzed enamine chemistry in a Michael addition to obtain chiral precursor 193 that gave vertinolide s tetronic ring (194) afler ketahzation, oxidation to lactone, and elimination (Scheme 1.31) [108]. After 4years, Matsuo and Sakaguchi [109] employed their chiral l,3-dioxolan-4-one 195 to obtain the central unsaturated lactone 196 after side-chain functionalization and condensation with triethyl-2-phosphonopropionate derived anion. Finally, in 2006, Takabe and coworkers [110], based on their previous work on the synthesis of racemic vertinolide, applied a lipase-catalyzed resolution on a 5-hydroxymethylene derivative of 197 to reach the natural enantiomer after five more synthetic steps (Scheme 1.31). 

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