Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

Hayama, Naomi; Azuma, Takumi; Kobayashi, Yusuke; Takemoto, Yoshiji

doi:10.1248/cpb.c15-00983

Cited by 40 publications

(16 citation statements)

References 31 publications

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“…Catalyst 3 and the monomeric counterpart catalyst 4 were synthesized according to standard procedures with more insight on the macrocycle’s role in the catalysis by comparing their catalytic activities. The corresponding isothiocyanates 7a and b were coupled with monoprotected ( R , R )-1,2-cyclohexanediamine 8 , followed by deprotection (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based Primary Amine Thiourea

et al. 2018

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An upper-rim functionalized calix[4]arene-based thiourea installed onto the ( R, R)-1,2-cyclohexanediamine scaffold was synthesized with a view to investigate its catalytic ability in enantioselective Michael additions. The reactions were found to conveniently proceed under solvent-free conditions, observing good to high enantioselectivities. From this preliminary study, the calix[4]arene unit is likely to play a role in affecting the conversion and to a lesser extent to the stereochemical outcome of the reactions through van der Waals contacts and C-H···π interactions with the substrates.

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Section: Resultsmentioning

confidence: 99%

Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based Primary Amine Thiourea

et al. 2018

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“…Furthermore, several asymmetric reactions with aliphatic carboxylic acids using chiral organoboron and organosilane complexes have been reported [10] . Moreover, we have been involved in the asymmetric hetero‐Michael additions to α,β‐unsaturated carboxylic acids and have developed chiral thiourea–amino boronic acid hybrid catalysts and a dual catalytic system comprising an arylboronic acid and a chiral aminothiourea [11a–c] (Scheme 1‐3). In the course of these projects, mechanistic studies (kinetics, NMR titration experiments, and computational studies) revealed that high enantioselectivity was attributed to asynchronous concerted face‐selective nucleophilic addition at the β‐position and carboxylic acid‐mediated protonation at the α‐position [11d] .…”

Section: Methodsmentioning

confidence: 99%

Novel Aza‐Michael Addition‐Asymmetric Protonation to α,β‐Unsaturated Carboxylic Acids with Chiral Thiourea‐Boronic Acid Hybrid Catalysts

et al. 2021

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Novel aza-michael addition-asymmetric protonation to unsaturated carboxylic acids with chiral thioureaboronic acid hybrid catalysts. #asymmetric protonationIn this study, an efficient method has been developed for controlling carbonyl α-chirality with functionalizing βposition by the conjugate addition-asymmetric protonation (CAAP) of α,β-unsaturated carboxylic acids using chiral thiourea-amino boronic acid hybrid catalysts. In addition, the method is applied to the asymmetric synthesis of biologically active compounds.Carbonyl compounds that are adjacent to a chiral tertiary carbon center are common structures in pharmaceuticals and natural products. Due to their ubiquity, numerous studies have analyzed the asymmetric synthesis of this important substructure. Asymmetric protonation of enolates is one of the most versatile methods for fabricating chiral carbonyl α-carbon centers. Thus, the enantioselective protonation of preformed enolates, such as metal enolate or silyl enol ether, has been investigated using stoichiometric amounts of chiral proton sources or chiral catalysts (Scheme 1-1). [1,2] Furthermore, another attractive approach with β-functionalization is the combination of the Michael addition and the enantioselective α-protonation of the resulting enolates (Scheme 1-2). To date, such transformation using unsaturated aldehyde, ketone, ester, amide, and others as Michael acceptors has been successfully studied. [3,4] However, to the best of our knowledge, the CAAP reaction of α,β-unsaturated carboxylic acids has not yet been reported, despite their chemical stability and availability as starting materials.Due to their improved stability to enzymatic hydrolysis, peptides containing β-amino acids are commonly found in pharmaceuticals and biopolymers. [5] β-Amino acids are mainly classified as five categories: β 2 , β 2,2 β 2,3 , β 3 , and β 3,3 -amino acids. Although catalytic asymmetric synthesis of β-amino acid derivatives has been well developed, the direct transformation of α,β-unsaturated carboxylic acids into chiral β 2 -amino acids is [a

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“…The best results in term of the yield (83%) and ee (90%) were obtained while using the catalyst having a p -nitrophenyl group on the other side of thiourea moiety in CCl 4 in the presence of 4 Å molecular sieves ( Table 16 ). The yields ranged 57–89% with ee 70–97% [ 52 ].…”

Section: Reviewmentioning

confidence: 99%

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

Sharma

Bansal

2021

Beilstein J. Org. Chem.

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Nitrogen-containing scaffolds are ubiquitous in nature and constitute an important class of building blocks in organic synthesis. The asymmetric aza-Michael reaction (aza-MR) alone or in tandem with other organic reaction(s) is an important synthetic tool to form new C–N bond(s) leading to developing new libraries of diverse types of bioactive nitrogen compounds. The synthesis and application of a variety of organocatalysts for accomplishing highly useful organic syntheses without causing environmental pollution in compliance with ‘Green Chemistry” has been a landmark development in the recent past. Application of many of these organocatalysts has been extended to asymmetric aza-MR during the last two decades. The present article overviews the literature published during the last 10 years concerning the asymmetric aza-MR of amines and amides catalysed by organocatalysts. Both types of the organocatalysts, i.e., those acting through non-covalent interactions and those working through covalent bond formation have been applied for the asymmetric aza-MR. Thus, the review includes the examples wherein cinchona alkaloids, squaramides, chiral amines, phase-transfer catalysts and chiral bifunctional thioureas have been used, which activate the substrates through hydrogen bond formation. Most of these reactions are accompanied by high yields and enantiomeric excesses. On the other hand, N-heterocyclic carbenes and chiral pyrrolidine derivatives acting through covalent bond formation such as the iminium ions with the substrates have also been included. Wherever possible, a comparison has been made between the efficacies of various organocatalysts in asymmetric aza-MR.

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Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

Cited by 40 publications

References 31 publications

Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based Primary Amine Thiourea

Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based Primary Amine Thiourea

Novel Aza‐Michael Addition‐Asymmetric Protonation to α,β‐Unsaturated Carboxylic Acids with Chiral Thiourea‐Boronic Acid Hybrid Catalysts

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

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