Cesium Fluoride-Induced Intramolecular Michael Addition:  Highly Diastereoselective Ring Construction of atrans-2,3-Dimethylchroman-4-one

We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.<br>

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Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

10.26434/chemrxiv.11481834.v1 ◽

2019 ◽

Author(s):

Nobutaka Fujieda ◽

Miho Yuasa ◽

Yosuke Nishikawa ◽

Genji Kurisu ◽

Shinobu Itoh ◽

...

Keyword(s):

Michael Addition ◽

In Silico ◽

Addition Reaction ◽

Single Point ◽

Point Mutations ◽

Unsaturated Ketone ◽

Michael Addition Reaction ◽

Beta Barrel ◽

Cupin Superfamily ◽

Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

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Enantioselective Michael Addition of Malonates to Enones

Current Organic Chemistry ◽

10.2174/1385272824666200316122221 ◽

2020 ◽

Vol 24 (7) ◽

pp. 746-773

Author(s):

Péter Bakó ◽

Tamás Nemcsok ◽

Zsolt Rapi ◽

György Keglevich

Keyword(s):

Michael Addition ◽

Activity Relationship ◽

Chalcone Derivatives ◽

Michael Additions ◽

Michael Reactions ◽

Structure Activity ◽

Cyclic Enones ◽

Michael Acceptors ◽

Relationship Of ◽

Enantioselective Catalysts

: Many catalysts were tested in asymmetric Michael additions in order to synthesize enantioenriched products. One of the most common reaction types among the Michael reactions is the conjugated addition of malonates to enones making it possible to investigate the structure–activity relationship of the catalysts. The most commonly used Michael acceptors are chalcone, substituted chalcones, chalcone derivatives, cyclic enones, while typical donors may be dimethyl, diethyl, dipropyl, diisopropyl, dibutyl, di-tert-butyl and dibenzyl malonates. This review summarizes the most important enantioselective catalysts applied in these types of reactions.

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