Chiral Bifunctional Squaramide‐Catalyzed Highly Enantioselective Michael Addition of Allomaltol to β,γ‐Unsaturated α‐Ketoesters

Abstract

A highly enantioselective Michael addition of allomaltol (5‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one) to both aromatic and aliphatic β,γ‐unsaturated α‐ketoesters has been realized. Under the catalysis of a chiral bifunctional tertiary amine‐squaramide that bears a (1R,2R)‐1,2‐diphenylethane‐1,2‐diamine scaffold, the reaction proceeded smoothly with high levels of enantioselectivity to give the desired products in acceptable yields with 86–>99 % enantiomeric excess. This methodology provided an efficient process for the enantioselective synthesis of optically active kojic acid derivatives.

Forty Years after “Heterodiene Syntheses with α,β-Unsaturated Carbonyl Compounds”: Enantioselective Syntheses of 3,4-Dihydropyran Derivatives

“…Squaramides (1R,2R)-CIX and (1R,2R)-CXXXI are the organocatalysts of the reactions of 2-oxo-4-phenylbut-3enoates 17 with cyclic 1,3-diketones 574a 277 or 591, the enolic form of a cyclic 1,2-diketone. 290 These reactions occur through the reacting intermediate type A reported in Scheme 350, in which the bifunctional organocatalyst coordinates both the CO groups of 17 by a double hydrogen bond, while the protonated tertiary amine binds the nucleophile anion. The structure of the bifunctional organocatalyst brings the nucleophile to approach the β-Si face of the electrophile, rationalizing the formation of (S)-580 and (S)-594, respectively (Scheme 350).…”

“…The further step was the reaction of 17 with allomaltol ( 591 ), the enolic form of a cyclic 1,2-diketone whose interest is the strong relationship with bioactive kojic acid derivatives. Two organocatalysts were tested, (1 R ,2 R )- CXXXI and (1 S ,2 R ,1′ R ,4a′ S ,10a′ R )- CXXXII , and the products were ( S )- 594 and its enantiomer ( R )- 594 , respectively. , The reagents, catalysts, and products of these reactions are illustrated in Schemes and , while the corresponding yields and enantioselectivities are listed in Table . The average reaction yields ranged from moderate values (63%) to very good values (93%), while the average ee was always excellent (up to 99%).…”

“…Squaramides (1 R ,2 R )- CIX and (1 R ,2 R )- CXXXI are the organocatalysts of the reactions of 2-oxo-4-phenylbut-3-enoates 17 with cyclic 1,3-diketones 574a or 591 , the enolic form of a cyclic 1,2-diketone . These reactions occur through the reacting intermediate type A reported in Scheme , in which the bifunctional organocatalyst coordinates both the CO groups of 17 by a double hydrogen bond, while the protonated tertiary amine binds the nucleophile anion.…”

Polymeric p–n Nanojunctions: Formation and Electrochemical Properties of C60‐Pd@Polypyrrole Core–Shell Nanoparticles

“…The β,γ‐unsaturated α‐keto esters, when reacted with certain nucleophiles bearing a hydroxy group, afford the corresponding Michael adducts, which are in equilibrium with the anomeric cyclized products formed by a hemiacetalization. The bifunctional amino‐squaramides also emerged as excellent catalysts for such a cascade Michael addition/hemiketalization sequence of enolizable 1,3‐carbonyl compounds,66 4‐hydroxycoumarins,66,67 4‐hydroxypyrone,66,67 2‐hydroxy‐1,2‐naphthoquinone,66,68,69 1‐naphthols,70 allomaltol,71 kojic acids,71 and pyrazolones,72 with β,γ‐unsaturated α‐keto esters (Table 1).…”

Construction of Bicyclo[3.2.1]octanes with Four Stereogenic Centers by Organocatalytic Domino Michael/Aldol Reaction

“…This coordination increases their reactivity, and the use of an organocatalyst would induce enantioselectivity in the reaction. Thanks to these characteristics, β,γ-unsaturated 1,2-dicarbonyl compounds, in particular α-ketoesters, have known widespread utilization in organocatalytic domino reactions forming polysubstituted chiral molecules. , In 2007, the Tang group reported an asymmetric organocatalytic [3 + 3]-annulation of six-membered cyclic enones onto β,γ-unsaturated 1,2-ketoesters forming chiral bicyclo[3.3.1]octanes . They extended their methodology to cyclopentanone as a nucleophile giving the formation of bicyclo[3.2.1]octane in high yield but with moderate enantioselectivity.…”