Low-loading asymmetric organocatalysis

Giacalone, Francesco; Gruttadauria, Michelangelo; Agrigento, Paola; Noto, Renato

doi:10.1039/c1cs15206h

Cited by 330 publications

(165 citation statements)

References 272 publications

(118 reference statements)

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“…[5] In this investigation, we explored the Henry reaction catalyzed by trifunctional squaramide 3, since it represents a clear example of a complex and effective catalytic system (Scheme 1).…”

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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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: 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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“…In conclusion, we here introduced inert octahedral 3-aminopyrazolato iridium(III) complexes as a novel class of Brønsted base catalysts and demonstrated their merit with the application to the asymmetric low-loading sulfa-Michael (down to 0.02 mol% catalyst loading) and aza-Henry reaction (down to 0.25 mol% catalyst loading) 15 . The high performance of the developed dual activation catalysts reveals the promise of octahedral metal complexes as chiral structural templates for Asymmetric aza-Henry reaction.…”

Section: Discussionmentioning

confidence: 99%

“…The advent of asymmetric organocatalysis over the last decade has consequently witnessed large activities in the development of chiral Brønsted acid and base catalysts [15][16][17][18][19] . Interestingly, with respect to chiral Brønsted base catalysis, although such chiral Brønsted bases have been reported as powerful catalysts for a range of asymmetric transformations, the vast majority of such catalysts is based on a limited number of basic functional groups-mainly tertiary amines, amidines and guanidines, and more recently also cyclopropenimines 20 and iminophosphoranes 21 (Fig.…”

mentioning

confidence: 99%

Metal-templated chiral Brønsted base organocatalysis

Ding

et al. 2014

Nat Commun

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Inert octahedral chiral-at-metal complexes are an emerging class of asymmetric catalysts that exploit the globular, rigid nature and stereochemical options of octahedral compounds. While the central transition metal serves as a structural anchorpoint and provides metal centrochirality, catalysis is mediated through the organic ligand sphere, thereby merging the branches of transition metal catalysis and organocatalysis. Here we report the development of inert octahedral 3-aminopyrazolato iridium(III) complexes as novel chiral Brønsted base catalysts and demonstrate their merit with applications to highly effective asymmetric sulfaMichael and aza-Henry reactions, permitting catalyst loadings down to 0.02 and 0.25 mol%, respectively. The observed high stereocontrol can be rationalized by a bifunctional mode of action in which the iridium catalyst, after the initial proton transfer, controls a ternary complex through defined hydrogen bonding interactions. This work reveals the potential of octahedral metal complexes as chiral scaffolds for the design of high-performance asymmetric catalysts.

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“…Over the past decade, asymmetric organic catalysis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], quite powerful for synthesizing various heterocyclic molecules, has formed the basis of several elegant approaches to construct chiral single-heterocycle piperidine skeletons with high efficiency and low toxicity under environmentally friendly conditions . In contrast, relatively few organocatalytic methods have been described to stereo-selectively form spirocyclic piperidine derivatives [30][31][32][33][34][35][36], particularly ones with a quaternary stereocenter [37][38][39].…”

Section: Introductionmentioning

confidence: 99%

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

et al. 2017

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A highly enantioselective organocatalytic Wolff rearrangement-amidation-Michaelhemiaminalization stepwise reaction is described involving a cyclic 2-diazo-1,3-diketone, primary amine and α,β-unsaturated aldehyde. Product stereocontrol can be achieved by adjusting the sequence of steps in this one-pot multicomponent reaction. This approach was used to synthesize various optically active spirocyclic piperidones with three stereogenic centers and multiple functional groups in good yields up to 76%, moderate diastereoselectivities of up to 80:20 and high enantioselectivities up to 97%.

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Low-loading asymmetric organocatalysis

Cited by 330 publications

References 272 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

Metal-templated chiral Brønsted base organocatalysis

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

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