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

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Organic Chemistry, Copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.joc.3c00763.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 N-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, trans di-substituted aziridine silanols give products with an erythro configuration; conversely, cis di-substituted aziridine silanols give products with a threo 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

Synthesis of a potential steroid intermediate by anionic oxy-cope rearrangement

The synthesis of the tricyclic ketol 6̲ which is a potential intermediate for non-aromatic steroids has been achieved via an anionic oxy-Cope rearrangement

A new synthesis of angularly substituted bicyclic systems via an anionic oxy-cope rearrangement

A general synthesis of trans bicyclic carbinols with an angular methyl substituent using the anionic oxy-Cope rearrangement is reported. The carbinols 13a̲ ,13b̲ ,14a̲ ,14b̲ and 15̲ furnish the bicyclic carbinols 16a̲, 16b̲, 17a̲, 17b̲ and 18̲ when treated with potassium hydride in 1,2-dimethoxyethane