Nucleophilic aliphatic aziridines

Two modes of reactivity could be envisioned (Scheme 41.20). It is likely that the reaction of aliphatic aziridines with TT nucleophiles as activated alkenes proceeds by an acid mediated 8 2 ring opening of the aziridine followed by nitrogen attack to the formed carbocation Com-... 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

Additions of nucleophiles to vinyl aziridines provide the issue of selectivity of 1,2 (Sn2) or 1,4 (Sn2 ) additions. During a very short efficient synthesis of pancratistatin, Hudlicky et al. chose to open a vinylaziridine 156 with an aromatic cuprate 157 <1996JA10752>. Formation of the trans-, Z adduct 158 was accomplished in 75% chemical yield (Equation 42). They found that the addition of simple lower order cuprates or Grignard reagents (aliphatic or aromatic) reacted to give the syn-, A addition, whereas higher-order cuprates gave the trans-, Z product. 

Recently, Schmitz has reported aminations of weak nucleophiles such as alkenes to produce aziridines directly. Although simple aliphatic olefins do not react, styrene, indene, acrylonitrile, and norbornene were converted to aziridines. The reaction of 3-ethyl-3-methyloxaziridine with diphenylcyclopropenone may be a reaction of this type. ... 

Wolff (1912) was the first to observe the ring expansion of phenyl azide, on thermolysis in aniline, to a compound he called dibenzamil (45). It was many years before this compound was shown to be 2-anilino-3if-azepine. This reaction was also found to take place on photolysis of aryl azides in primary and secondary aliphatic amines. The mechanism that was proposed and which has since been generally accepted involves nucleophilic attack by solvent on a benzazirine, that is believed to be in equilibrium with singlet arylnitrene. Nmr evidence has been advanced for the intermediacy of a 1/f-azepine (46) in related expansions which, as expected, rapidly isomerizes to the more stable tautomer. Spectroscopic evidence is still lacking for the aziridine intermediate 47, but this could simply be due to its short lifetime. On the other hand, the recent work of Chapman and Le Roux discussed in Section 1.4 has brought into question the intermediacy of benzazirine in phenyl... 

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