Organocatalytic asymmetric conjugate addition of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-ketoesters

Abstract

The conjugate addition of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-keto-esters was studied using a series of chiral bifunctional organocatalysts. Takemoto's catalyst was found to be most efficient for this transformation. Excellent yields and good enantioselectivities were achieved for a variety of β,γ-unsaturated α-keto-esters and cyclic 1,3-dicarbonyl compounds. A bifunctional catalytic mechanism is proposed. The method provides a new asymmetric synthetic route for chiral courmarin derivatives.

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…A dimethylamine derivative appeared to be a versatile promoter, active in various asymmetric transformations: Michael reaction of nitroolefins and malonates [136] or 1,3-dicarbonyl compounds [137], active methylene compounds with α,βunsaturated imides [138,139], aza-Henry [140], Neber reaction (synthesis of azirine derivatives) [141], aldol reaction [142], and others [110][111][112]. Now commercially available (in both (R,R)-and (S,S) forms), Takemoto's organocatalyst was also used by other groups, mainly to catalyze various stereoselective additions [135,[143][144][145][146][147][148][149][150], and to control the ring-opening polymerization of racemic lactide leading to highly isotactic polylactide [151].…”

“…Various modified derivatives of Takemoto's catalyst were tested in the enantioselective reduction of ketones with borane; a benzyl-substituted catalyst led to the best outcomes [156]. A piperidine derivative showed the optimal performance among diamine-derived catalysts tested in inverse-electrondemand Diels-Alder cycloaddition [157], Mannich reaction of 2-substituted indolin-3-ones [158], and pyrrolidine-substituted thiourea, in conjugated addition of nitroacetates to unsaturated ketoesters [159], and in double Michael reaction used for the construction of a spiro-fused cyclohexanone-5- Now commercially available (in both (R,R)-and (S,S) forms), Takemoto's organocatalyst was also used by other groups, mainly to catalyze various stereoselective additions [135,[143][144][145][146][147][148][149][150], and to control the ring-opening polymerization of racemic lactide leading to highly isotactic polylactide [151].…”

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

“…In addition to the synthetic protocols reported above, several other reactions were performed involving γ,δ-unsaturated α-keto esters 17 or arylidene-2-acetylpyridine N -oxide 20 , with 4-hydroxycoumarin 541 or 4-hydroxy-2 H -pyran-2-one ( 563a ), catalyzed by either the chiral complexes or organocatalysts CXV-CXXI reported in Chart . The results in terms of number of examples, average yields, and average enantioselectivity are listed in Table . − A few different enolic nucleophiles have also been tested, somewhat related to 541 or 563a , 563b , 568 , and 570 , whose reaction products are reported in Chart , and the results, of not leading importance, are also listed in Table . Depending on the reaction conditions, the products isolated from these reactions are described as Michael adducts or cyclic hemiketals.…”

Organocatalytic Asymmetric Conjugate Addition and Cascade Acyl Transfer Reaction of α-Nitroketones

“…α-Nitroketones are readily deprotonated by many weak bases to generate enolate anions. In addition, α-nitroketones can be converted into a number of useful functionalized compounds via different derivation pathways. , Recently we have developed a series of organocatalytic conjugate additions with various nucleophiles . We speculate that α-nitroketones are valuable nucleophiles for organocatalytic asymmetric conjugate additions.…”