Diversity-Oriented Synthesis of N, N, O- Trisubstituted Hydroxylamines from Alcohols and Amines by N-O Bond Formation

Jarvis Hill; Asiri A Hettikankanamalage; David Crich

doi:10.1021/jacs.0c05991

Diversity-Oriented Synthesis of N, N, O- Trisubstituted Hydroxylamines from Alcohols and Amines by N-O Bond Formation

J Am Chem Soc. 2020 Sep 2;142(35):14820-14825. doi: 10.1021/jacs.0c05991. Epub 2020 Aug 24.

Authors

Jarvis Hill^{1

2}, Asiri A Hettikankanamalage^{1

2}, David Crich^{1

2

3}

Affiliations

¹ Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.
² Department of Chemistry, University of Georgia, 140 Cedar Street, Athens, Georgia 30602, United States.
³ Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States.

PMID: 32803971
DOI: 10.1021/jacs.0c05991

Abstract

Magnesium dialkylamides react with alcohol-derived 2-methyl-2-tetrahydropyranyl alkyl peroxides (MTHPs) in tetrahydrofuran at 0 °C to give N,N,O-trisubstituted hydroxylamines suitable for medicinal chemistry purposes in good to excellent yields. A wide range of secondary alkyl and aryl amines and primary and secondary alcohol-derived MTHPs are compatible with the described reaction which, coupled with the enormous diversity of commercially available alcohols and secondary amines, suggests broad applicability of the reaction in fragment-based library design.