[3 + 3]-Carbocyclizations of nitroallylic esters and enamines with stereoselective formation of up to six new stereogenic centers

Seebàch, Dieter; Missbach, Martin; Calderari, Giorgio; Eberle, Martin

doi:10.1021/ja00177a026

Cited by 95 publications

(36 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both cycloheptenone and acetone did not work in the current catalytic reaction (entries 11 and 12). Since Seebach et al have reported that the enamine of either cycloheptenone or acetone can react with nitroolefin very well to afford the corresponding product, [7] these results suggested that the formation of the enamines from both cycloheptenone and acetone can be sluggish. Aliphatic nitroolefin was less active than aromatic nitroolefin in the current reaction.…”

Section: Resultsmentioning

confidence: 99%

“…The relative configurations of products 6 a and 6 b were determined by X-ray diffraction analysis (Scheme 4). [9] The reaction mechanism of enamine derived from cyclic ketones with nitroallylic carbonyl compounds has been well stud- ied by Seebach et al [7] On the basis of the mechanistic insight, the aforementioned asymmetric tandem reaction can be explained as outlined in Scheme 2. The formation of intermediate A by means of enamine catalysis facilitates the first Michael addition, followed by an elimination of acetate to afford B.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, these particular compounds have never been used for organocatalytic asymmetric cascade reactions, although they have been combined with chiral enamines for a formal [3+3] carbocyclization. [7] We speculated that under the catalysis of suitable aminocatalysts, the combination of nitroallylic acetates 1 with cyclic ketone 2 might spontaneously undergo Michael/elimination/ Michael reactions to give the bicycle [3.3.1] skeletons with four or five chiral centers. In this paper, we wish to report our efforts on this subject in detail.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons

Cao

Zhou

et al. 2009

Chemistry A European J

104

View full text Add to dashboard Cite

Cyclic ketones react with (E)-2-nitroallylic acetates in the presence of catalytic pyrrolidine-thiourea, which affords bicyclic skeletons with four or five stereocenters in one single reaction with up to 98 % ee in moderate to high yields. The cooperative effects of both enamine and the Brønsted acid are found to be crucial for the high reactivity and enantioselectivity of this cascade reaction, which is demonstrated by both theoretical calculation and experimental data.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons

Cao

Zhou

et al. 2009

Chemistry A European J

104

View full text Add to dashboard Cite

show abstract

“…With cyclohexanone, the si face of the enamine is shielded, therefore the reaction takes place on the re face, to give 2S stereochemistry in the product. According to Seebach's model, [25][26][27][28][29][30][31] the nitroolefin approaches the enamine in a synclinal fashion, due to the favorable electrostatic interactions between the partially positive nitrogen atom of the enamine in the transition state and the partially positive nitro group. Thus the (R)-1-configuration is obtained and the product therefore has syn stereochemistry.…”

Section: Resultsmentioning

confidence: 99%

α‐Aminophosphonates as novel organocatalysts for asymmetric Michael addition of carbonyl compounds to nitroolefins

et al. 2008

View full text Add to dashboard Cite

show abstract

“…To explain the syn-diastereoselectivity and the absolute configuration observed, we propose transition state I based on Seebachs model for the dipeptide-catalyzed asymmetric Michael additions. [20] The acid moiety and the amide bond of the dipeptide plausibly assist in the stabilization of the transition state, which is improved by a small amount of water.…”

Section: Communicationsmentioning

confidence: 99%

Small Peptide‐Catalyzed Enantioselective Addition of Ketones to Nitroolefins

et al. 2006

View full text Add to dashboard Cite

Abstract:The direct small peptide-catalyzed enantioselective Michael addition of ketones to nitroolefins is presented. Simple di-and tripeptides derived from alanine catalyze the asymmetric Michael additions with high stereoselectivity and furnish the corresponding Michael products in high yield with up to 68 : 1 dr and 98% ee. The study demonstrates that small, readily prepared peptides with increased structural complexity as compared to the parent amino acid mediate the asymmetric Michael reaction with superior reactivity and enantioselectivity.Keywords: asymmetric catalysis; ketones; Michael reaction; nitroolefins; peptides The Michael addition is a fundamental carbon-carbon bond-forming reaction in organic synthesis.[1] Therefore, chemists have developed several catalytic asymmetric protocols for this important reaction.[2] In recent years, an intense research effort has been made to find nontoxic chiral organic molecules as catalysts for enantioselective reactions.[3] For example, Miller [4] and Jacobsen [5] have employed catalytic peptides and peptide-like molecules as catalysts for asymmetric additions. Their structural diversity, availability and modularity could make them ideal asymmetric organocatalysts for a variety of transformations.[6] Proline [7] and N-terminal prolylpeptides [8] have been described as catalysts for the asymmetric Michael reaction. However, only moderate enantioselectivity is typically obtained. For example, proline and N-terminal prolyldipeptides catalyze the asymmetric formation of g-nitroketones with 5 -76% ee and 0 -31% ee, respectively. Proline-derived derivatives have been proven to be more succesful for the asymmetric Michael reaction. [9 -12] Recently, Alexakis, [13] Kotsuki, [14] Wang [15] and Hayashi [16] reported excellent highly enantioselective Michael conjugate additions that were catalyzed by chiral pyrrolidine-based catalysts. However, they are generally more complex and prepared in more steps than a simple amino acid or peptide catalysts. Herein, we present that simple dipeptides with a catalytic primary amine residue catalyze the direct asymmetric Michael addition of ketones to nitroolefins with high stereoselectivity and furnish the corresponding g-nitro ketones with up to 68 : 1 dr and 98% ee.Based on our research interest in asymmetric catalysis, [17] we recently found that acyclic aliphatic amino acids catalyze asymmetric intermolecular aldol reactions and Mannich reactions with high stereoselectivities.[18] The lessons from these studies made us interested in whether acyclic amino acids as well as small peptides derived from them could react with a ketone and form a catalytic chiral enamine, which could serve as a nucleophile in Michael additions to nitroolefins [Eq. (1)]. We expected that addition of a small excess of water would increase the efficiency and circumvent the need of adding an acidic additive. In addition, water would facilitate hydrogen bonding and proton transfer, which could plausibly improve the enantioselectivity of the Michael reaction. ð...

show abstract

[3 + 3]-Carbocyclizations of nitroallylic esters and enamines with stereoselective formation of up to six new stereogenic centers

Cited by 95 publications

References 6 publications

An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons

An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons

α‐Aminophosphonates as novel organocatalysts for asymmetric Michael addition of carbonyl compounds to nitroolefins

Small Peptide‐Catalyzed Enantioselective Addition of Ketones to Nitroolefins

Contact Info

Product

Resources

About