Aminomethylation Grignard reagents

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Aminomethylation. The reagent reacts with Grignard reagents to form N,N-bis(trimethylsilyl)amines in 60-90% yield (equation I). A similar reaction with organo-lithium compounds requires added magnesium bromide for satisfactory yields.1... 

The bromination of ethyl (aminomethyl)methylphosphinate followed by alkylation gives the phosphinic ester (236). As an alternative to the use of a Grignard reagent in the latter step, coupling can be achieved using a lithium-copper complex. (235a) is the precursor to the mixed phosphonic-phosphinic triester (237). ... 

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