- Stereoselective construction of a quaternary carbon substituted with multifunctional groups: Application to the concise synthesis of (+)-ethosuximide
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Synthetically useful β,γ-unsaturated carbonyl compounds having a quaternary carbon at the α-position were prepared with high stereoselectivity by the reaction of a dienolate anion derived from α,β-unsaturated imide having a chiral auxiliary and electrophiles (ethyl acetate and allyl iodide as the C2 and C3 unit, respectively). This method was applied to a short asymmetric synthesis of (+)-ethosuximide.
- Abe, Tomoaki,Suzuki, Tatsuo,Sekiguchi, Kazuhiko,Hosokawa, Seijiro,Kobayashi, Susumu
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- Catalytic reductive desymmetrization of malonic esters
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Desymmetrization of fully substituted carbons with a pair of enantiotopic functional groups is a practical strategy for the synthesis of quaternary stereocentres, as it divides the tasks of enantioselection and C?C bond formation. The use of disubstituted malonic esters as the substrate of desymmetrization is particularly attractive, given their easy and modular preparation, as well as the high synthetic values of the chiral monoester products. Here, we report that a dinuclear zinc complex with a tetradentate ligand can selectively hydrosilylate one of the carbonyls of malonic esters to give α-quaternary β-hydroxyesters, providing a promising alternative to the desymmetric hydrolysis using carboxylesterases. The asymmetric reduction features excellent enantiocontrol that can differentiate sterically similar substituents and high chemoselectivity towards the diester motif of substrates. Together with the versatile preparation of malonic ester substrates and post-reduction derivatization, the desymmetric reduction has enabled the synthesis of a diverse array of quaternary stereocentres with distinct structural features. [Figure not available: see fulltext.]
- Xu, Pengwei,Huang, Zhongxing
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p. 634 - 642
(2021/06/14)
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- Diphenylprolinol silyl ether catalyzed asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes for the construction of all-carbon quaternary stereogenic centers
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The asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β-substituents such as β-aryl and β-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.
- Hayashi, Yujiro,Kawamoto, Yuya,Honda, Masaki,Okamura, Daichi,Umemiya, Shigenobu,Noguchi, Yuka,Mukaiyama, Takasuke,Sato, Itaru
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p. 12072 - 12082
(2015/03/31)
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- A new divergent asymmetric synthesis of (+)- and (-)-ethosuximides and their anticonvulsant activities
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Both enantiomers of ethosuximide were synthesized divergently from nitroolefin lactone [(-)-2a] or [(-)-2b], which was obtained by asymmetric nitroolefination of α-methyl-γ-butyrolactone with chiral nitro enamines derived from L-proline. Although anticonv
- Katoh, Takahiro,Nishide, Kiyoharu,Node, Manabu,Ogura, Hiroo
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p. 833 - 841
(2007/10/03)
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- Direct gaschromatographic separation of drug racemates
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For inspection of the direct separability of synthetic drug racemates through GC/MS a uniform scheme is proposed and checked with 35 drugs and two cyclodextrin capillary columns. All investigated analytes vaporized without decomposition, 26 of them are separable in the enantiomers, among them 10 with separation to the baseline and 14 with CO-NH-structure.
- Schleuder,Duerrbeck,Jira
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p. 381 - 386
(2007/10/03)
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- Synthesis of (+)- and (-)-ethosuximides utilizing asymmetric nitroolefination
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Both enantiomers of ethosuximide were synthesized from (S)-(-)- and (R)-(+)-2-methyl-2-[(E)-2-nitroethenyl]-γ-butyrolactones (1), which were obtained by asymmetric nitroolefination of α-methyl-γ-butyrolactone, via the lactone carboxylic acid (3).
- Nishide, Kiyoharu,Katoh, Takahiro,Imazato, Hitoshi,Node, Manabu
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p. 839 - 845
(2007/10/03)
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