Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles

OTEVŘEL, Jan, David ŠVESTKA a Pavel BOBÁĽ. Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles. In 55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021. 2021.

Základní údaje

• Originální název: Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles
• Autoři: OTEVŘEL, Jan (203 Česká republika, domácí), David ŠVESTKA (203 Česká republika, domácí) a Pavel BOBÁĽ (703 Slovensko, domácí).
• Vydání: 55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021, 2021.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Prezentace na konferencích
• Obor: 30104 Pharmacology and pharmacy
• Stát vydavatele: Česká republika
• Utajení: není předmětem státního či obchodního tajemství
• Kód RIV: RIV/00216224:14160/21:00123871
• Organizační jednotka: Farmaceutická fakulta
• Klíčová slova česky: sodium bis(2-methoxyethoxy)aluminium hydride (SMEAH); vicinální aminoalkohol; C-H hydroxylace
• Klíčová slova anglicky: sodium bis(2-methoxyethoxy) aluminum hydride (SMEAH); vicinal aminoalcohol; C-H bond hydroxylation

Anotace

As a result of our long-term interest in developing H-bond donor organocatalysts, we have prepared many chiral non-racemic amine scaffolds by reducing the corresponding enantiopure amides1. For such transformations, sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH) is often used as a safer alternative to LiAlH4. Interestingly, (S)-naproxamide subjected to the above reduction conditions provided a curious product, which was then identified as the respective 1,2-amino alcohol derivative2. We found out that, in general, amides and nitriles of aryl-alkanoic acids bearing at least one hydrogen atom at benzylic position exhibit a unique reactivity towards SMEAH under O2 atmosphere. The substrate scope of this process was examined on 30 entries. Even though the respective products were provided in moderate yields only, the simple operating procedure may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult or laborious to prepare by other routes. The plausible mechanistic proposal for the observed results was given based on the isolation and identification of the stable intermediates and stereochemical evidence. The present method may open up attractive prospective routes for future developments in 18O-labeling strategies or stereoselective synthesis thereof. The reaction was applied to a synthesis of a potentially bioactive target.

Návaznosti

• LM2015043, projekt VaV: Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology