Enantioselective synthesis of γ-aminobutyric acid derivatives by Ni(II)-catalyzed reaction of diethyl malonate with nitroalkenes

Shiryaev

Reznikov³

et al. 2018

Synthesis

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.

Section: Paper Syn Thesismentioning

confidence: 77%

“…Previously we showed the use of Ni(II) catalyzed addition of diethyl malonate to nitrostyrene 25 and nitropropene 26 in the asymmetric synthesis of (R)-phenotropil (4) and (3R)-4-amino-3-methylbutyric acid, respectively. 26 However, there are still no examples of the use of adamantane-containing nitroalkenes in these reactions.…”

Section: Syn Thesismentioning

confidence: 99%

Asymmetric Synthesis of Adamantyl GABA Analogues

Shiryaev

Reznikov³

et al. 2018

Synthesis

“…The most remarkable results were obtained with Ni(II) complexes as catalyst for the Michael addition of 1,3-dicarbonyl compounds to nitroalkenes [47–54]. This reaction was used as a key stage in the synthesis of non-racemic analogues of GABA and substituted pyrrolidinones with neurotropic activity [47,51–52 54].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

Reznikov

Beilstein J. Org. Chem.

Baimuratov

et al. 2019

Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the catalytic Michael reaction itself was carried out with high diastereoselectivity, but the Michael adducts may epimerize at the C-2 position at a significant rate. Conditions for the preparation of individual diastereomers were found.

“…The strategy for the synthesis of chiral Michael adducts, [19 -26] based on the use of nickel complexes with chiral ligands, was applied to obtain non-racemic GABA derivatives, [27] polysubstituted cyclohexanes, [28] and piperidin-2-ones. [29] We have also shown that Ni(II) complexes with chiral diamines are active catalysts in asymmetric conjugate addition of other Michael donors, such as β-oxo phosphonates [30] and β-oxo sulfoxides.…”

Section: Introductionmentioning

confidence: 99%

Nitroalkenes in the Ni(II) Catalyzed AsymmetricMichaelAddition. Convenient Route to the Key Intermediate of Brivaracetam

Reznikov

Ivankina

et al. 2018

Helvetica Chimica Acta

A series of Ni(II) complexes with novel chiral ligands derived from (1R,2R)‐1,2‐diphenylethane‐1,2‐diamine was synthesized. The catalytic activity of these complexes in the asymmetric Michael reaction is demonstrated. Asymmetric addition of diethyl malonate to ω‐nitrostyrene and 1‐nitropent‐1‐ene in the presence of these complexes leads to the enantiomerically enriched diethyl (S)‐2‐(2‐nitro‐1‐phenylethyl)malonate (up to 96 % ee) and (R)‐diethyl 2‐(1‐nitropenthan‐2‐yl)malonate (up to 91 % ee). (4R)‐4‐Propylpyrrolidin‐2‐one, the key intermediate of antiepileptic drug brivaracetam, was obtained from the corresponding nitroester.