Azaphilic addition

JHC1163>. Inverse addition of CH3Li to the tetrazine solution yielded (24). Grignard compounds also show azaphilic addition. ... 

The azaphilic addition of organometallic reagents on 1,2,4,5-tetrazines has been studied. Depending on the nature of the metal, azaphilic addition, reduction of the tetrazine or simple complex formation, was the predominant transformation and usually high selectivity was observed <04T1991>. Reaction of 3,6-diphenyl-l,4-dihydro-l,2,4,5-tetrazine with isobutyric anhydride yielded l-isobutyryl-3,6-diphenyl-l,4-dihydro-l,2,4,5-tetrazine and its structure was elucidated by X-ray analysis <04JCR(S)408>. 

Work by Kotschy and co-workers showed that reactions of different symmetrical 1,2,4,5-tetrazines with a variety of organometallic reagents furnished, depending upon the combination of reactants, azaphilic addition, reduction or complexation products and not the nucleophilic aromatic substitution products <2004T1991>. On the other hand, Benson et al. reported a smooth displacement of one chlorine substituent in chlorotetrazine 136 using cyanide anion as a soft C-nucleophile (Scheme 36) <2000T1165>. 

Coordination of a Lewis acid to the amide nitrogen of acylaziridines catalyzes a rearrangement to the oxazoline, whereas coordination to the carbonyl oxygen is better at activating the substrate toward external nucleophilic attack. More azaphilic salts, Zn(OTf)2, Cu(OTf)2, and Sn(OTf)2, do not catalyze the addition of nucleophiles to acylaziridines, but instead promote the rearrangement of acylaziridines to 2-aryloxa-zolines (Eq. 16) [25]. 

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