Reevaluation of the Mechanism of the Baylis–Hillman Reaction: Implications for Asymmetric Catalysis

Aggarwal, Varinder K.; Fulford, Sarah Y.; Lloyd‐Jones, Guy C.

doi:10.1002/ange.200462462

Cited by 62 publications

(26 citation statements)

References 21 publications

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“…Based on the above experimental results, we propose that a water molecule participates in the 1,3-proton transfer. [17] The key hydrogen-bonding interactions between the NH group of the amide and the pyrazolone enolate is crucial for the stereochemical outcome of the reaction (see the transition state depicted in Table 3). When water was added to the reaction system, the hydrogen-bond network was disrupted, and erosion of enantioselectivity was observed.…”

Section: Methodsmentioning

confidence: 99%

Asymmetric Synthesis of Spiropyrazolones through Phosphine‐Catalyzed [4+1] Annulation

et al. 2014

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An enantioselective synthesis of spiropyrazolones from allenoate-derived MBH acetates and pyrazolones through a phosphine-mediated [4+1] annulation process has been developed. Spiropyrazolones were readily prepared in good chemical yields and good to high enantioselectivities. This is the first asymmetric example in which a-substituted allenoates were utilized as a C 4 synthon for phosphine-catalyzed [4+1] annulation.Over the past decade, nucleophilic phosphine catalysis has emerged as a powerful approach to structurally diverse and synthetically valuable carbocyclic and heterocyclic building blocks in organic chemistry. [1] Pioneered by Lu and coworkers, [2] different types of phosphine-catalyzed cycloaddition reactions have been developed over the years. In particular, [3+2] annulations of allenoates/alkynes or Morita-Baylis-Hillman (MBH) acetate/carbonates with alkenes or imines have been widely explored and established as an effective method for contructing a wide range of highly functionalized five-membered ring systems. [3] However, other types of [m+n] annulations were studied to a much lesser extent, [4] and the discovery of different cyclization modes with novel reaction partners is highly desirable.Phosphine-catalyzed [4+1] annulations represent an alternative approach for the formation of five-membered ring systems, and the successful development of this type of annulation is dependent on careful selection and utilization of C 4 and C 1 synthons for the projected cyclization. Recently, MBH carbonates were used as a new C 1 synthon in phosphine-catalyzed [4+1] annulations for the construction of five-membered heterocyclic ring structures by Zhang, [5] Chen, [6] and He. [7] Mechanistically, all the above reactions are initiated by the addition of a phosphine to an MBH carbonate to in situ generate a 1,1-dipolar synthon, which reacts with various conjugated electrophilic reaction partners. Another type of [4+1] annulation was disclosed by Tong in 2010, [8] in which 2,3-butadienoate, an a-substituted allenoate, was utilized as a C 4 synthon under phosphine catalysis, affording cyclopentene products (Scheme 1). Asymmetric versions of [4+1] annulations are very scarce; to the best of our knowledge, there is only one report in the literature. Shi utilized dicyano-2-methylenebut-3-enoates as a C 4 synthon in the annulation reaction with MBH carbonates, for the asymmetric synthesis of highly functionalized cyclopentenes. [9] However, the utilization of a-substituted allenoates in asymmetric [4+1] annulations is unknown. It thus became our goal to develop an asymmetric variant of this promising transformation.Pyrazolone and their derivatives are important structural motifs that widely occur in biologically active molecules and pharmaceutical agents, [10] and they are also synthetically valuable for the construction of heterocyclic and spirocyclic structures. [11] Recently, 4-spiro-5-pyrazolones were found to be inhibitors of type-4 phosphodiesterase, [12] resulting in the need for efficient synthetic approaches ...

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Section: Methodsmentioning

confidence: 99%

Asymmetric Synthesis of Spiropyrazolones through Phosphine‐Catalyzed [4+1] Annulation

et al. 2014

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“…In the past decades, remarkable advances in this area have led to the discovery of several new catalysts with superior activities and enantioselectivities [12 -20] . Meanwhile, efforts have also been made to investigate the reaction mechanism [21][22][23][24][25][26][27][28][29][30][31] . Generally, the reaction is catalyzed by a tertiary amine or tertiary phosphine, and the commonly accepted mechanism is shown in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Bifunctional catalysis of Morita-Baylis-Hillman (MBH) reaction with chiral primary-tertiary diamine: A non-typical MBH catalytic pathway

Zhang

Luo

Chen

et al. 2009

Sci. China Ser. B-Chem.

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“…The following proton transfer is the key step (rate-determining step) on the basis of previous literature. [12] We believe that the acidic proton of the C-6'-OH group serves as a "proton shuttle" to facilitate the intramolecular proton transfer from the acarbon to the oxygen anion. A plausible transitionstate model C indicating the favorable key proton transfer step via intramolecular proton relay is also shown in Scheme 3.…”

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confidence: 99%

Enantioselective Intermolecular Rauhut–Currier Reaction of Electron‐Deficient Allenes with Maleimides

et al. 2011

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Abstract:The 1,4-diazabicyclicA C H T U N G T R E N N U N G [2.2.2]octane (DABCO)-catalyzed intermolecular Rauhut-Currier reaction of maleimides with electron-deficient allenes has been investigated, affording the corresponding products in good to high yields under mild conditions. The first example of a b-isocupreidine (b-ICD)-catalyzed highly enantioselective intermolecular Rauhut-Currier reaction of male-A C H T U N G T R E N N U N G imides with allenoates and penta-3,4-dien-2-one has been also developed, allowing the synthesis of optically active functionalized allene derivatives in good to high yields along with good to excellent enantioselectivities.The Rauhut-Currier (RC) reaction, also known as vinylogous Morita-Baylis-Hillman (MBH) reaction, involves the coupling of one active alkene/latent enolate to a second Michael acceptor, producing a new C À C bond between the a-position of one activated alkene and the b-position of a second alkene under the catalysis of a nucleophilic species.[1] This reaction was first reported by Rauhut and Currier in 1963 in the dimerization of electron-deficient alkenes catalyzed by tertiary phosphine.[1b] A few years later, a series of phosphine-catalyzed intermolecular RC reactions was subsequently explored, demonstrating the wide synthetic utility of this reaction.[2] Moreover, in 1986, Amri and Villieras [3] first disclosed that tertiary amines such as 1,4-diazabicyclicA C H T U N G T R E N N U N G [2.2.2]octane (DABCO) could also efficiently catalyze the intermolecular RC reactions under mild conditions and since then, this type of tertiary amine-catalyzed intermolecular RC reactions has been further developed by Basavaiah and co-workers as well as other researchers during the last decades.[4] The first asymmetric version of an intermolecular Rauhut-Currier reaction was presented by Wang and co-workers using a Cinchona alkaloid thiourea as a catalyst in a novel asymmetric Michael-Michael cascade reaction of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl ester with transb-nitrostyrene in 2008.[5] Almost at the same time, scandium triflate [ScA C H T U N G T R E N N U N G (OTf) 3 ] combined with (R,R)-Phpybox was used as a catalyst by Scheidt and co-workers in an intermolecular RC reaction of silyloxyallenes with a,b-unsaturated ketones, affording the corresponding product in 72% yield, 20:1 (Z:E) and 70% ee.[6] However, to the best of our knowledge, there has been no report on the asymmetric intermolecular RC reaction involving electron-deficient alkenes with allenes promoted by the amine-based organocatalyst, although enantioselective intramolecular RC-type reactions have achieved a great progress in recent years. [7,8] In this paper, we would like to disclose the application of quinidine-derived b-isocupreidine (b-ICD) as organocatalyst for the asymmetric intermolecular RC reaction of maleimides with electron-deficient allenes, giving the corresponding products in high yields and good to high ee values under mild conditions. We initiated our investigations by seeking ...

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Reevaluation of the Mechanism of the Baylis–Hillman Reaction: Implications for Asymmetric Catalysis

Cited by 62 publications

References 21 publications

Asymmetric Synthesis of Spiropyrazolones through Phosphine‐Catalyzed [4+1] Annulation

Asymmetric Synthesis of Spiropyrazolones through Phosphine‐Catalyzed [4+1] Annulation

Bifunctional catalysis of Morita-Baylis-Hillman (MBH) reaction with chiral primary-tertiary diamine: A non-typical MBH catalytic pathway

Enantioselective Intermolecular Rauhut–Currier Reaction of Electron‐Deficient Allenes with Maleimides

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