Diastereoselective Construction of the 6-Oxa-2-azabicyclo[3.2.1]octane Scaffold from Chiral α-Hydroxyaldehyde Derivatives by the Aza-Prins Reaction

Alejandro Mahía; Ramón Badorrey; José A Gálvez; María D Díaz-de-Villegas

doi:10.1021/acs.joc.7b01291

Diastereoselective Construction of the 6-Oxa-2-azabicyclo[3.2.1]octane Scaffold from Chiral α-Hydroxyaldehyde Derivatives by the Aza-Prins Reaction

J Org Chem. 2017 Aug 4;82(15):8048-8057. doi: 10.1021/acs.joc.7b01291. Epub 2017 Jul 26.

Authors

Alejandro Mahía¹, Ramón Badorrey¹, José A Gálvez¹, María D Díaz-de-Villegas¹

Affiliation

¹ Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza , Departamento de Química Orgánica, Pedro Cerbuna 12, 50009 Zaragoza, Spain.

PMID: 28715633
DOI: 10.1021/acs.joc.7b01291

Abstract

(R)-2,3-Di-O-benzylglyceraldehyde and N-tosyl homoallylamine undergo aza-Prins cyclization to afford (1R,5S,7S)-7-[(benzyloxy)methyl]-2-tosyl-6-oxa-2-azabicyclo[3.2.1]octane in a highly diastereoselective manner through an unexpected intramolecular nucleophilic attack. Our work has opened a new route toward the asymmetric synthesis of 7-(alkyl or aryl)-6-oxa-2-azabicyclo[3.2.1]octane derivatives from chiral α-hydroxyaldehyde derivatives in one step.

Publication types

Research Support, Non-U.S. Gov't