Enantioselective Michael Addition: An Experimental Introduction to Asymmetric Synthesis

10.26434/chemrxiv.11336525.v1 ◽

2019 ◽

Author(s):

Martin Tiano

Keyword(s):

Undergraduate Students ◽

Michael Addition ◽

Enantiomeric Excess ◽

Diethyl Malonate ◽

2D Nmr ◽

Shift Reagent ◽

Experimental Session ◽

H Nmr ◽

Asymmetric Michael Addition ◽

Chiral Lewis Acid

We adapted a classical asymmetric Michael addition for a 1-day experimental session (6-8 hrs) for third or fourth-year undergraduate students. The experiment follows up three steps : synthesis of a chiral Lewis Acid, LiAl(BINOL)2, then its use as a catalyst in the Michael addition of diethyl malonate on cyclopentenone, followed by purification through column chromatography on silica gel. The desired product can be fully characterized by 1D and 2D NMR experiments and IR spectroscopy. The enantiomeric excess can be determined by polarimetry and 1H NMR using chiral lanthanide shift reagent Eu(hfc)3.

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Asymmetric Michael Addition of Diethyl Malonate to Chalcone Derivatives

Asymmetric Organocatalysis 2 ◽

10.1055/sos-sd-205-00421 ◽

2012 ◽

pp. 1

Author(s):

S. Shirakawa ◽

K. Maruoka

Keyword(s):

Michael Addition ◽

Diethyl Malonate ◽

Chalcone Derivatives ◽

Asymmetric Michael Addition

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Asymmetric Synthesis of Adamantyl GABA Analogues

Synthesis ◽

10.1055/s-0037-1610824 ◽

2018 ◽

Vol 51 (02) ◽

pp. 463-469 ◽

Cited By ~ 1

Author(s):

Anastasiya Sibiryakova ◽

Vadim Shiryaev ◽

Alexander Reznikov ◽

Anastasiya Kabanova ◽

Yuri Klimochkin

Keyword(s):

Asymmetric Synthesis ◽

Michael Addition ◽

Diethyl Malonate ◽

Efficient Synthesis ◽

Synthetic Strategy ◽

Asymmetric Michael Addition ◽

Gaba Analogues ◽

Sterically Hindered

An efficient synthesis of (R)- and (S)-4-amino-3-(adamant-1-yl)butyric acids and (R)- and (S)-4-(adamant-1-yl)pyrrolidin-2-ones is presented. The synthetic strategy is based on asymmetric Michael addition of diethyl malonate to 1-(adamant-1-yl)-2-nitroethene using available Ni(II) complex as the catalyst. The procedures provide good to high enantioselectivity of Michael addition to sterically hindered nitroalkene and good yields of (R)- and (S)-enantiomers of 3-adamantyl substituted GABA.

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The Bull–James assembly as a chiral auxiliary and shift reagent in kinetic resolution of alkyne amines by the CuAAC reaction

Organic & Biomolecular Chemistry ◽

10.1039/c6ob01623e ◽

2016 ◽

Vol 14 (46) ◽

pp. 10778-10782 ◽

Cited By ~ 10

Author(s):

William D. G. Brittain ◽

Brette M. Chapin ◽

Wenlei Zhai ◽

Vincent M. Lynch ◽

Benjamin R. Buckley ◽

...

Keyword(s):

Nmr Spectroscopy ◽

Boronic Acid ◽

Kinetic Resolution ◽

Enantiomeric Excess ◽

Shift Reagent ◽

Chiral Auxiliary ◽

H Nmr ◽

Chiral Shift Reagent ◽

Cuaac Reaction

The Bull–James boronic acid assembly is used simultaneously as a chiral auxiliary for kinetic resolution and as a chiral shift reagent for in situ enantiomeric excess (ee) determination by 1H NMR spectroscopy.

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Synthesis and Recovery of Pyridine- and Piperidine-based Camphorsulfonamide Organocatalysts Used for Michael Addition Reaction

Periodica Polytechnica Chemical Engineering ◽

10.3311/ppch.12719 ◽

2018 ◽

Vol 62 (4) ◽

Cited By ~ 1

Author(s):

Péter Kisszékelyi ◽

Sándor Nagy ◽

Blanka Tóth ◽

Bálint Zeller ◽

László Hegedűs ◽

...

Keyword(s):

Biological Activity ◽

Organic Solvent ◽

Michael Addition ◽

Addition Reaction ◽

Enantiomeric Excess ◽

Michael Addition Reaction ◽

Michael Adduct ◽

Asymmetric Michael Addition ◽

Organic Solvent Nanofiltration ◽

Moderate Yield

Two new pyridine-based asymmetric bifunctional organocatalysts containing one or two camphorsulfonamide units were synthesized. Asymmetric Michael addition of pentane-2,4-dione to β-nitrostyrene was catalyzed by these organocatalysts. During our experiments, influence of the solvent and temperature on the yield and enantioselectivity was studied. Using monocamphorsulfonamide derivative the S enantiomer of the corresponding Michael adduct was gained with moderate yield (up to 51 %) and low enantiomeric excess (up to 18 %). Organic solvent nanofiltration was successfully applied for the recovery of these organocatalysts. Furthermore, pyridine camphorsulfonamide was reduced to its piperidine derivative. Using piperidine monosulfonamide derivative racemic Michael adduct was obtained with excellent yield (up to 89 %). Beside its organocatalytic relevance, piperidine monosulfonamide derivative may also possess biological activity.

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