Synthesis ofcis-C-Iodo-N-Tosyl-Aziridines using Diiodomethyllithium: Reaction Optimization, Product Scope and Stability, and a Protocol for Selection of Stationary Phase for Chromatography

Abstract

The preparation of C-iodo-N-Ts-aziridines with excellent cis-diastereoselectivity has been achieved in high yields by the addition of diiodomethyllithium to N-tosylimines and N-tosylimine–HSO2Tol adducts. This addition-cyclization protocol successfully provided a wide range of cis-iodoaziridines, including the first examples of alkyl-substituted iodoaziridines, with the reaction tolerating both aryl imines and alkyl imines. An ortho-chlorophenyl imine afforded a β-amino gem-diiodide under the optimized reaction conditions due to a postulated coordinated intermediate preventing cyclization. An effective protocol to assess the stability of the sensitive iodoaziridine functional group to chromatography was also developed. As a result of the judicious choice of stationary phase, the iodoaziridines could be purified by column chromatography; the use of deactivated basic alumina (activity IV) afforded high yield and purity. Rearrangements of electron-rich aryl-iodoaziridines have been promoted, selectively affording either novel α-iodo-N-Ts-imines or α-iodo-aldehydes in high yield.

tert-Butanesulfinamides as Nitrogen Nucleophiles in Carbon–Nitrogen Bond Forming Reactions

“…20), [37] and the lithium or potassium anions of dihalo methanes (21). [38] It is also important to mention that condensation of sulfur ylides [39] as well as tellurium ylides [40] with N-tert-butanesulfinyl imines is a related process that has also been used to develop some efficient stereoselective synthetic approaches to Ntert-butanesulfinyl aziriridines.…”

Unprotected Aziridines: A Synthetic Overview

“…A number of methods have been developed for the synthesis of N‐protected aziridines. The vast majority of these methods afford N‐protected aziridines that contain a strongly electron‐withdrawing group on the nitrogen atom; as such, these syntheses require an additional deprotection step, which is not an easy task, because they often result in the unwanted opening of the aziridine ring.…”

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

“…We have been interested in the preparation of iodoaziridines as a novel functional group that offers the potential to provide precursors to a wide range of derivatives with complementary reactivity to existing aziridine functionalization reactions. In 2012 we reported the first preparation of aryl N-Boc-iodoaziridines 20 , and very recently reported the preparation of aryl and alkyl substituted N-Ts-iodoaziridines 21 .…”

“…Due to the sensitive nature of the iodoaziridines, we established a protocol to assess the stability of a compound to an array of stationary phases 21 , which is demonstrated here. This has potential for application in the synthesis of a wide range of compounds with sensitive functional groups.…”