Trifunctional Squaramide Catalyst for Efficient Enantioselective Henry Reaction Activation

Alegre‐Requena, Juan V.; Marqués‐López, Eugenia; Herrera, Raquel P.

doi:10.1002/adsc.201600046

Cited by 45 publications

(34 citation statements)

References 50 publications

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“…[6] We performed some additional experiments using catalyst 5, which is identical to 3 except in that it has a OMe group instead of a OH group (Table 4). The results showed changes of only 2-8% yield and 2-5% ee when using catalyst 5 instead of catalyst 3.…”

Section: Role Of the Oh Group In Squaramidementioning

confidence: 99%

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Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

Alegre‐Requena

Marqués‐López

Herrera

2017

Chemistry A European J

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This study represents the first example where the accuracy of different combinations of density functional theory (DFT) methods and basis sets has been compared in squaramide catalysis. After an optimization process of the precision obtained and the computational time required in the computational calculations, highly precise results were achieved compared to the experimental outcomes while using the least amount of time as possible. Here, we have explored computationally and experimentally the mechanism of squaramide-catalyzed Henry reaction. This is a complex reaction of about 100 atoms and a great number of diverse non-covalent interactions. Moreover, this research is one of the scarce examples where the organocatalyst acts in a trifunctional manner and is the first investigation in which a trifunctional squaramide catalyst has been employed. Functional ωB97X-D showed the best results when used with different versions of the 6-311 basis sets, leading to highly accurate calculations of the outcomes of the Henry reaction using nine aldehydes with different structural characteristics. Furthermore, in these relatively large systems, the use of a split-valence triple-zeta basis set saves a large amount of time compared to using larger basis sets that are sometimes employed in organocatalytic studies, such as the TZV and Def2TZV basis set families.

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Section: Role Of the Oh Group In Squaramidementioning

confidence: 99%

“…[6] In addition, this is a large system in which the catalyst-substrate complex contains around 100 atoms. The catalyst activates the reaction creating interactions with the substrates mainly through three different groups: an amino, a squaramido and a naphthyl group (trifunctional catalysis).…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

Alegre‐Requena

Marqués‐López

Herrera

2017

Chemistry A European J

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“…The binaphthyl structural motif has already been employed in the hydrogen-bond-donating organocatalysis [ 35 – 36 ]. However, the binaphthol moiety possessing an additional hydrogen bond donor group was not tested in too much depth.…”

Section: Resultsmentioning

confidence: 99%

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

Vargová

Baran

Šebesta

2018

Beilstein J. Org. Chem.

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Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er.

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“…Asymmetric organocatalysts were employed in both the Henry reaction and aza-Henry reaction in the early 2000s [ 37 , 38 ]. Since then, researchers have sought to expand the reaction scope and reaction conditions, testing new chiral organocatalysts such as squaramide [ 39 ], thiourea derivatives [ 40 ], proline derivatives [ 41 ], and bipyridine derivatives [ 42 ]. Like the aldol reaction, Henry reactions are often used in tandem with Michael reactions [ 40 , 41 , 43 , 44 ].…”

Section: Henry Reactionsmentioning

confidence: 99%

Recent Advances in Organocatalyzed Domino C–C Bond-Forming Reactions

Evans

Davis

2017

Molecules

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Reactions that form a C–C bond make up a foundational pillar of synthetic organic chemistry. In addition, organocatalysis has emerged as an easy, environmentally-friendly way to promote this type of bond formation. Since around 2000, organocatalysts have been used in a variety of C–C bond-forming reactions including Michael and aldol additions, Mannich-type reactions, and Diels–Alder reactions, to name a few. Many of these methodologies have been refined and further developed to include cascade and domino processes. This review will focus on recent advances in this area with an emphasis on methodologies having applications in the synthesis of biologically-significant compounds.

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Trifunctional Squaramide Catalyst for Efficient Enantioselective Henry Reaction Activation

Cited by 45 publications

References 50 publications

Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

Recent Advances in Organocatalyzed Domino C–C Bond-Forming Reactions

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