An unexpected tandem enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters catalyzed by cinchona alkaloids

Wang, Haifeng; Zheng, Changwu; Yang, Ying‐Quan; Chai, Zhuo; Zhao, Gang

doi:10.1016/j.tetasy.2008.11.007

Cited by 19 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition a modified Cinchona alkaloid catalyst, in which the C-9eOH was substituted with a phenyl group, was also tested. 26 Of all the eight catalysts examined, quinine 1 (Q) provided the best results in terms of both yield and enantioselectivity. According to the proposed mechanism (Scheme 6), quinine first catalysed the asymmetric Michael addition of 15 and 16 via dual activation of both electrophile and nucleophile (transition-state I) to produce intermediate II, which then underwent an oxanucleophilic attack at the carbonyl group of 15, generating another intermediate III.…”

Section: Michael Addition Reactionsmentioning

confidence: 98%

Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

2011

View full text Add to dashboard Cite

Section: Michael Addition Reactionsmentioning

confidence: 98%

Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

2011

View full text Add to dashboard Cite

“…[10] We report herein the development of several amino acid-derived thiourea-tertiary amine catalysts and their applications to the asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters.…”

mentioning

confidence: 99%

Highly Enantioselective Michael Addition of Cyclic 1,3‐Dicarbonyl Compounds to β,γ‐Unsaturated α‐Keto Esters

et al. 2010

Self Cite

View full text Add to dashboard Cite

A highly enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters catalyzed by amino acid-derived thiourea-tertiary-amine catalysts is presented. Using 5 mol% of a novel tyrosine-derived thiourea catalyst, a series of chiral coumarin derivatives were obtained in excellent yields (up to 99%) and with up to 96% ee under very mild conditions within a short reaction time.Keywords: 1,3-dicarbonyl compounds; Michael addition; organocatalysts; thioureas; b,g-unsaturated a-keto esters Increased focus has recently been placed on the application of organocatalysis in reactions allowing the rapid construction of functionalized molecules from simple and readily available starting materials.[1] In this field, the asymmetric Michael addition of 1,3-cyclic dicarbonyl compounds to a,b-unsaturated carbonyl systems, which could provide many chiral compounds with biological and pharmaceutical activities such as neo-flavonoids and coumarins, has attracted much attention.[2] As a class of activated a,b-unsaturated carbonyl systems, b,g-unsaturated a-keto esters sometimes are preferred electrophiles in this kind of reaction due to their high reactivity and the easy convertibility of the resultant products to other useful structures.[3] In 2003, Jørgensen et al. reported the enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters catalyzed by chiral bisoxazoline-copper(II) complexes with moderate to high enantioselectivities.[4] However, it was not until very recently that an similar organocatalyzed reaction between cyclic diketones and b,g-unsaturated a-keto esters using Cinchona alkaloid-derived pyrimidines was reported by Calter et al. [5] In contrast, several organocatalysts have been developed for the Michael addition of cyclic diketones to a,b-unsaturated ketones, in which the "imine catalysis" usually controls the enantioselectivity. [6] On the other hand, following the pioneering works of Jacobsen and Takemoto, [7] remarkable advances have been made in the development and application of bifunctional chiral thiourea catalysts in catalytic asymmetric reactions. [8] Recently, the use of inexpensive and readily available amino acids as the chiral scaffold to develop novel thiourea catalysts has attracted considerable interest and proved to be effective in several asymmetric reactions.[9] Our group has been interested in the development of organocatalytic reactions utilizing b,g-unsaturated a-keto esters as a reaction partner to synthesize useful compounds. [10] We report herein the development of several amino acid-derived thiourea-tertiary amine catalysts and their applications to the asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters.Using the reaction between (E)-methyl 2-oxo-4-phenylbut-3-enoate (3a) and 4-hydroxycoumarin (4a) as the model reaction, a series of thiourea-tertiary amine catalysts (Figure 1) was evaluated and the results are summarized in Table 1. Similar to Takemotos ca...

show abstract

“…The absolute configuration of the product is reported in entry 4 of Table : excellent yield and satisfactory enantioselectivity were obtained, and the structure was confirmed by X-ray analysis. Several other products were obtained in poor yields with ee’s up to 82% …”

Section: Michael Reactionsmentioning

confidence: 99%

“…Two reactions have been catalyzed with quinine derivatives. Equation 5: ( S,R )- XII catalyzes the Henry reaction between 1 and 22 to give ( R )- 25 through attack to the CO- Re face of 1 Equation 6: ( S,R )- XXXV catalyzes the cascade Michael reaction between 1 and 77 to give ( S )- 78 through attack to the β- Si face of 1 …”

Section: Relationship Between Different Chiral Small Molecules Acting...mentioning

confidence: 99%

See 1 more Smart Citation

Substituted (E)-2-Oxo-3-butenoates: Reagents for Every Enantioselectively-Catalyzed Reaction

2013

View full text Add to dashboard Cite

show abstract

An unexpected tandem enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters catalyzed by cinchona alkaloids

Cited by 19 publications

References 51 publications

Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

Highly Enantioselective Michael Addition of Cyclic 1,3‐Dicarbonyl Compounds to β,γ‐Unsaturated α‐Keto Esters

Substituted (E)-2-Oxo-3-butenoates: Reagents for Every Enantioselectively-Catalyzed Reaction

Contact Info

Product

Resources

About