Ring Opening of Aziridines by Pendant Silanols Allows for Stereospecific Preparations of 1′-Amino-tetrahydrofurans

Abstract

We have developed a highly stereospecific cyclization of aziridine silanols into 1'-amino-tetrahydrofurans. Our protocol of stirring a substrate with 10 mol % Sc (OTf)₃ and 1 equivalent of NaHCO₃ in CH₂Cl₂ is mild and compatible with a range of activating aziridine <i>N</i>-substituents (including tosylates, mesylates, and carbamates) and functional groups on the alkyl chains (including substituted aryl rings, alkyl bromides, and alkyl ethers). In all cases examined, <i>trans</i> di-substituted aziridine silanols give products with an <i>erythro</i> configuration; conversely, <i>cis</i> di-substituted aziridine silanols give products with a <i>threo</i> configuration. While literature syntheses of 1'-amino-tetrahydrofurans exist, only one example, contemporaneous with our work, uses a similar cyclization for their construction. Control experiments demonstrate that, for this transformation, the silanol is not particularly privileged, and a variety of protecting groups on the alcohol (including other silicon protecting groups, benzyl ethers, and MOM ethers) are compatible with product formation.