Highly Enantioselective Michael Reactions Catalyzed by a Chiral Quaternary Ammonium Salt. Illustration by Asymmetric Syntheses of (<i>S</i>)-Ornithine and Chiral 2-Cyclohexenones

Zhang, Fuyao; Corey, E. J.

doi:10.1021/ol0056527

Cited by 172 publications

(87 citation statements)

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“…[3] Corey et al first reported the conjugate addition of 1 to acrylates and enones with notable enantioselectivity (> 90 % ee) in the presence of an Nalkylated cinchonidine salt. [4] Subsequently, the scope of the reaction was expanded with other modified cinchona alkaloids [5] as well as new catalysts, comprising largely of quaternary bis(ammonium) and N-spiro ammonium moieties derived from tartrates, [6] axially-chiral 1,1'-biaryl units, [5f, 7] inositol-derived crown ethers, [8] and a calix[4]arene amino acid. [9] The use of these pH-neutral catalysts requires strong bases to generate the nucleophile, thus very low temperatures (typically À40 to À78 8C) were necessary to suppress competitive reactions.…”

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confidence: 99%

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Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

et al. 2013

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Conjugate addition of glycine-derived imine esters (1) to Michael acceptors can generate highly functionalized molecules with up to three contiguous stereogenic centers (Scheme 1), which is an attractive strategy for assembling molecular complexity from achiral precursors in a single step without byproducts. [1] Presently, nonmetal-based phase-transfer catalysts (PTCs) and organocatalysts [2] have been deployed to great effect for these reactions. [3] Corey et al. first reported the conjugate addition of 1 to acrylates and enones with notable enantioselectivity (> 90 % ee) in the presence of an Nalkylated cinchonidine salt. [4] Subsequently, the scope of the reaction was expanded with other modified cinchona alkaloids [5] as well as new catalysts, comprising largely of quaternary bis(ammonium) and N-spiro ammonium moieties derived from tartrates, [6] axially-chiral 1,1'-biaryl units, [5f, 7] inositol-derived crown ethers, [8] and a calix[4]arene amino acid. [9] The use of these pH-neutral catalysts requires strong bases to generate the nucleophile, thus very low temperatures (typically À40 to À78 8C) were necessary to suppress competitive reactions.In contrast, deployment of catalysts containing planar nitrogen entities received far less attention. In 2001, Ishikawa et al. showed that the modified guanidine derivative 2 (Figure 1) can be employed as a chiral Brønsted superbase for Michael reactions. [10] The basicity of the catalyst allowed reactions to proceed under ambient conditions in good enantioselectivities, but reactions were sluggish. They required days to complete even without using any solvents, which may account for the lack of development of this type of catalyst in the ensuing decade. However, two recent breakthroughs have rekindled interest in this area, with independent reports of the pentanidium derivative 3 [11] and cyclopropenimine 4 [12] (Figure 1), which can deliver very favorable catalytic turnovers and enantioselectivities between room temperature and À20 8C.Herein, we describe the preparation of a family of structurally novel 2-oxopyrimidinium salts (5), and their performance as asymmetric PTCs in the conjugate addition of the glycine imine ester 1 a (R 1 = tBu) to vinyl ketone and chalcone derivatives.The structure of 5 is derived from chiral methylenebridged bis(imidazolines) (MBI), previously reported by Pfaltz and co-workers as a variant of bisoxazoline ligands for asymmetric catalysis. [13] The C 2 -symmetrical architecture was assembled in five steps from the N-Boc-protected amino acids 6 a-c (Scheme 2): the MBIs 10 a-j were prepared by a modified literature procedure, and subsequently treated with triphosgene to afford the 2-oxo-pyrimidinium salts 5. Single-crystal X-ray diffraction analysis of the n-butyl-substituted derivative 5 b (Figure 2) revealed planar fused rings, corroborating a highly mesomeric tricyclic system.The addition of the tert-butyl ester glycinate benzophenone Schiff base (1 a; Table 1) to MVK (11 a) in the presence of 5 a was chosen for reaction optimizat...

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“…Herein, we describe the preparation of a family of structurally novel 2-oxopyrimidinium salts (5), and their performance as asymmetric PTCs in the conjugate addition of the glycine imine ester 1 a (R 1 = tBu) to vinyl ketone and chalcone derivatives.…”

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confidence: 99%

Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

et al. 2013

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“…The absorbance values of the studied amino acid are given in table ( 2) and shown in figures 4, 5, and 6.…”

Section: Resultsmentioning

confidence: 99%

“…Altering the charge on amino acids and their derivatives by varying the pH facilitate the physical separation of amino acids, peptides and proteins. 2 The isoelectric species is the form of a molecule that has an equal number of positive and negative charges and thus is electrically neutral. The isoelectric pH, also called the pI is the pH midway between pKa values on either side of the isoelectric species.…”

Section: Introductionmentioning

confidence: 99%

Spectrophotometric determination of the ionization constant values (PKa ) of some amino acids (Methionine , cystine and cysteine )

Hasan¹,

Habib²

2017

ECB

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A simple, rapid and sensitive method has been applied on three amino acids viz., methionine, cystine and cysteine, to estimate the ionization constant. Spectrophotometric measurements were carried out on the absorbance of each amino acid at different pH values. The results showed that the cystine and cysteine have one pKa, while the methionine gave two different pKa values by using this method.* Corresponding Authors E-Mail: Drhamadmhasan85@yahoo.com [a]

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“…The addition of Schiff base to vinyl cyanide furnished the key precursor of ornithine in 91% ee. 79 Remarkably, the stereogenic center did not racemize under the reaction conditions, despite the high acidity of the proton of the chiral center.…”

Section: Synthesis Of 175mentioning

confidence: 95%

Organocatalytic Conjugate Addition in Stereoselective Synthesis

Quintard

Alexakis

2013

Stereoselective Synthesis of Drugs and Natural Products

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Conjugate addition is a privileged method in organic synthesis allowing for the formation of new CC bonds, molecules that can serve as valuable synthons for total synthesis. It is highly attractive thanks to the presence of at least one functional group on the Michael partners, a group that can be easily derivatized. In this field, organocatalyzed reactions have recently changed the way of thinking about synthetic approaches, notably, as soon as carbonyl groups are involved. As a result, numerous applications of organocatalytic Michael additions in natural product synthesis have emerged in the last few years.

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Highly Enantioselective Michael Reactions Catalyzed by a Chiral Quaternary Ammonium Salt. Illustration by Asymmetric Syntheses of (S)-Ornithine and Chiral 2-Cyclohexenones

Abstract: [formula: see text] The use of the chiral quaternary ammonium salts 1a and 1b makes possible enantioselective Michael reactions which have been applied to the asymmetric syntheses of (S)-ornithine (2) and the chiral 2-cyclohexenone 6.

Cited by 172 publications

References 10 publications

Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

Spectrophotometric determination of the ionization constant values (PKa ) of some amino acids (Methionine , cystine and cysteine )

Organocatalytic Conjugate Addition in Stereoselective Synthesis

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