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

k 2021

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

OTEVŘEL, Jan; David ŠVESTKA a Pavel BOBÁĽ

Základní údaje

Originální název

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

Autoři

OTEVŘEL, Jan; David ŠVESTKA a Pavel BOBÁĽ

Vydání

55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021, 2021

Další údaje

Jazyk

angličtina

Typ výsledku

Prezentace na konferencích

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ano

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

Změněno: 28. 4. 2022 13:45, JUDr. Sabina Gajdzioková

Anotace

V originále

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

Citovat

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.

@proceedings{1824588,
   author = {Otevřel, Jan and Švestka, David and Bobáľ, Pavel},
   booktitle = {55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021},
   keywords = {sodium bis(2-methoxyethoxy) aluminum hydride (SMEAH); vicinal aminoalcohol; C-H bond hydroxylation},
   language = {eng},
   title = {Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles},
   year = {2021}
}

TY  - CONF
ID  - 1824588
AU  - Otevřel, Jan - Švestka, David - Bobáľ, Pavel
PY  - 2021
TI  - Unexpected formation of 1-aryl-2-aminoalcohols during reductions of the corresponding amides and nitriles
KW  - sodium bis(2-methoxyethoxy) aluminum hydride (SMEAH)
KW  - vicinal aminoalcohol
KW  - C-H bond hydroxylation
N2  - 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.
ER  -

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

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