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

OTEVŘEL, Jan, David ŠVESTKA and 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.

Basic information

• Original name: Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles
• Authors: OTEVŘEL, Jan (203 Czech Republic, belonging to the institution), David ŠVESTKA (203 Czech Republic, belonging to the institution) and Pavel BOBÁĽ (703 Slovakia, belonging to the institution).
• Edition: 55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021, 2021.

Other information

• Original language: English
• Type of outcome: Presentations at conferences
• Field of Study: 30104 Pharmacology and pharmacy
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• RIV identification code: RIV/00216224:14160/21:00123871
• Organization unit: Faculty of Pharmacy
• Keywords (in Czech): sodium bis(2-methoxyethoxy)aluminium hydride (SMEAH); vicinální aminoalkohol; C-H hydroxylace
• Keywords in English: sodium bis(2-methoxyethoxy) aluminum hydride (SMEAH); vicinal aminoalcohol; C-H bond hydroxylation

Abstract

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.

Links

• LM2015043, research and development project: Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR