Grignard reagents, reaction with aziridines

When both a-positions of the oxime possess active hydrogen, the regiochemistry of the Hoch-Campbell reaction prefers the side with more available hydrogens— indicating the process is kinetically controlled. In case of oxime 36, azirine 37 was not formed. Instead, azirine 38 was obtained exclusively. Addition of the third equivalent of the Grignard reagent delivered aziridine 39 as a mixture of two diastereomers. 

This reaction is known as the Hoch-Campbell aziridine synthesis, which entails treatment of ketoximes with excess Grignard reagents and subsequent hydrolysis of the organometallic complex to produce aziridines. 

Trifluoromethyl derivatives of aziridine are intensively studied as biologically active substances. (Trifluoromethyl)aziridines 4 were prepared from (trifluoromethyl)ketoximes 3 and Grignard reagents (equation 2). However, this reaction is not general. For example, reaction does not occur with phenyl and allyl Grignard reagents, but when it works the Z stereoisomer is formed . 

Alvernhe and Laurent first developed a procedure for conversion of Grignard reagents to primary amines using acetone oxime 6c and butanone oxime 6d (Scheme 55) 22 23 However, the yields were low. They expanded their study to investigate how well organo-lithiums perform in their reaction with 6c or 6d 23. Phenyllithium gave a 1 4 mixture of aniline and the addition product of phenyllithium to the imine (Scheme 53, path e product) in the reaction with 6c while aziridine was obtained in the reaction with 6d (Scheme 56). 

When cyclohexanone oxime 6e was used as amination reagent, primary amines were obtained from phenylmagnesium bromide. Reaction of 6e with alkyl Grignard reagents gave aziridines, whereas reaction with phenyllithium gave aziridine and the addition product of phenyllithium to the imine (Scheme 57) 24. 

Azirines have also been shown to be likely intermediates in the Campbell aziridine synthesis.62 This reaction is analogous to the Neber reaction in which the intermediate azirine is hydrolyzed to the aminoketone. Here the proposed azirine intermediate prepared from oxime (144) reacts with a Grignard reagent to give the aziridine (145). 

The synthetically important subclass of alkynyl aziridines was included in a recent review <02COC539>, specifically from the standpoint of preparation and ring opening reactions with carbon nucleophiles. Such substrates (e.g. 178) tend to suffer Sn2 attack from Grignard reagents to give aminoallenes (e.g. 179). 

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