Asymmetric Michael Addition of β‐Ketoesters to Enones Catalyzed by the Lithium Salt of a Primary β‐Amino Acid

Abstract

A highly enantioselective Michael addition of β‐ketoesters to enones was achieved by using the salt of a readily available primary β‐amino acid as the catalyst. The obtained Michael adducts were converted into enantioenriched 1,5‐diketones in high yields through a common decarboxylation reaction under acidic conditions. A plausible reaction mechanism for the Michael addition reaction, which is supported by results of mechanistic studies that include DFT calculations, is also described.

Asymmetric α-Allylation of α-Substituted β-Ketoesters with Allyl Alcohols

“…Allyl alcohols 2a – d were purchased and used without purification. O -Silylated l -threonines ( 3a and 3b ) and β-homoserine 3c were synthesized according to the literature procedures; other amino acids 3d – g were purchased and used without purification. Palladium catalysts 4 and phosphine ligands were purchased and were used without purification.…”

“…Next, the screening of catalysts with amino acids 3 was examined in the presence of 4b and P­(4-FC 6 H 4 ) 3 , and Table summarizes the results obtained. When lipophilic primary amino acids, O -silylated threonines 3a , b and β-homoserine 3c , were used as catalysts, the allylation reaction proceeded readily to give 5a in high yield with high enantioselectivity. , Common primary and secondary amino acids 3d – g could not promote the allylation reaction due to low solubility in the solvent, and a large amount of 1a was recovered after the experiments. Using amino ester 3h , a methyl ester of 3a , as a catalyst, N -(2-ethoxycarbonylcyclopent-1-enyl) O -TBDPS- l -threonine methyl ester ( 6 ), an enamine generated from 1a and 3h , was obtained in 12% yield and no allylated product was generated.…”