Synthesis of Diaziridines and Diazirines via Resin-Bound Sulfonyl Oximes

Abstract

Diazirines are one of the most prominent functionalities in labeling experiments in vivo and in vitro because they allow photochemical generation of carbenes. The strategy presented herein describes the formation of diaziridines, being essential precursors in diazirine syntheses, using solid-supported procedures with immobilized sulfonyl oximes. The solid-supported building blocks have been shown to be valuable intermediates for CuAAC and amidation reactions, offering the possibility to build complex compounds with diverse functionalities.

Monitoring Reactions on Solid Phases with Raman Spectroscopy

“…As the monitoring of unknown procedures on solid phases is of crucial interest at several stages of synthesis, from attachment of the first building block to cleavage of the target compound, our first investigations covered the observation of the immobilisation of building blocks on commercial functionalised resins. Two of the most common polymeric starting materials, namely, sulfonyl chloride resin ( 1 ) and Merrifield resin ( 2 ), were used to show that Raman spectroscopy offers the opportunity to determine the necessary requirements for new synthetic techniques (e.g., immobilisation of ketoximes on a sulfonyl chloride resin) and allows one to reconsider the reaction parameters of well‐known reactions, such as the formation of triazene linkers. Therefore, Raman spectroscopy was used to establish the attachment of ketoxime building blocks to a commercially available resin through alteration of the reaction conditions.…”

“…Methods for the synthesis of triazenes, sulfonyl oximes and ether linkers on solid supports have been described earlier and are given in detail for selected examples in the Supporting Information. The general procedures and the single procedures, the description of the washing procedures for the isolation of solid‐supported material and figures showing monitoring of all reactions described in the schemes are also given in the Supporting Information.…”

New Trends in Diaziridine Formation and Transformation (a Review)

“…Recently, there have been two methods that have taken advantage of the conventional concept and turned it into brand new approaches to developing diaziridine synthesis. The first is the use of resin-bound sulfonyl oximes for the synthesis of 3-trifluoromethyl-3-phenyldiaziridine [76]. A commercially available polystyrene−sulfonyl chloride 82, used as an equivalent to replace the common reagents mesyl or tosyl chloride, was previously reacted with oxime 83 to provide the desired solid-supported sulfonyl oxime.…”

A Study of the Crystal Structure and Hydrogen Bonding of 3-Trifluoroacetyloxime Substituted 7-Acetamido-2-aryl-5-bromoindoles

“…Aqueous work-up and purification of the crude products by silica gel column chromatography afforded compounds characterized by means of NMR, IR, and mass spectrometric methods as the corresponding 3-trifluoroacetyloxime substituted 7-acetamido-2-aryl-5-bromoindole derivatives 3a-d. The latter are interesting because the α-trifluoromethylated ketoximes can be tosylated or mesylated and then cyclized into the corresponding diaziridines [22][23][24]. Diaziridines, on the other hand, have been found to readily undergo oxidation into diazirines, which are important in photoaffinity labelling experiments in vivo and in vitro due to their propensity to undergo photochemical reactions to generate carbenes [23,24].…”

“…The latter are interesting because the α-trifluoromethylated ketoximes can be tosylated or mesylated and then cyclized into the corresponding diaziridines [22][23][24]. Diaziridines, on the other hand, have been found to readily undergo oxidation into diazirines, which are important in photoaffinity labelling experiments in vivo and in vitro due to their propensity to undergo photochemical reactions to generate carbenes [23,24]. A single crystal of 3d was obtained by slow evaporation of a chloroform solution, and the molecular structure of compounds 3a-d was confirmed by X-ray diffraction analysis (CCDC No.…”