Aziridine ring

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

Transition metals have also been inserted into the aziridine ring affording derivatives (295). Stereochemical studies suggest that transfer of a proton is followed by bimolecular attack on the ring with subsequent closure on the carbonyl group (76AG(E)495). 

Aziridines can best be obtained by ring closure of amine derivatives which contain a tm 5-oriented leaving group at the -position, see (89). The variable conformational and steric influences in the steroid skeleton limit the generality of a particular synthetic method and necessitate a selection of reagents based on the position of fusion of the aziridine ring. 

The present authors have found that the preparation of 7V-acetyl aziridine derivates provides the most secure method of differentiating aziridines from primary amines which are alternate reaction products in a number of cases. The infrared spectra of the former derivatives show only a peak at 1690 cm" for a tertiary amide peaks at ca. 3440 and 1530 cm" indicative of a secondary amide are absent. Acetylation also shifts the aziridine ring protons to a lower field in the NMR by ca. 1 ppm relative to the parent aziridine. The A"-acetyl aziridines are hydrolyzed with 3% methanolic potassium hydroxide. " Published NMR spectra of several 16j5,17j -aziridines reveal resonance patterns resembling those of the respective epoxides. " ... 

Thermal rearrangement of 2-vinylaziridine 203, with an electron-withdrawing substituent on the nitrogen atom, at reflux in decalin predominantly yielded 2-pyr-roline 204 along with some 3-pyrroline derivatives 205 (Scheme 2.50) [79]. A similar reaction was also observed with l-alkyl-2-phenyl-3-vinylaziridines 206 [80]. From these observations, the nature of the products formed depends on the natures of the substituents on the aziridine ring if the ring carbon carries a phenyl substituent, the thermolysis in most cases preferentially yields 2-pyrrolines. 

Reductive aziridine ring-opening with sodium cyanoborohydride has been described [74, 91]. In the presence of a catalytic amount of TsOH, compound 111 (Scheme 3.37) gave 112 in 68% yield on treatment with sodium cyanoborohydride [74, 91]. 

In an attempt to effect a chloroformate-mediated dealkylation of aziridine lactone 119 (Scheme 3.41), Dodd and co-workers observed aziridine ring-opening, a-Chloro lactone 120 was obtained in 72% yield [32]. 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

Treatment of N-acetyl aziridinecarboxylate with acetic anhydride and heating resulted in the aziridine ring-opened product [106], whereas treatment of the aziridine 137 (Scheme 3.49) with acetic anhydride in the presence of pyridine and DMAP as base similarly resulted in the formation of acetate 138 in 90% yield [45]. 

N-Acylaziridine-2-carboxylates readily rearrange to oxazolines under thennal, acidic, or nucleophilic conditions [91, 123-127]. Treatment of trans-aziridine-2-car-boxylate 176 (Scheme 3.63) with Nal in acetonitrile, for example, resulted in ring-expansion product 177 through the so-called Heine reaction. The reaction involves initial opening of the aziridine ring by iodide and subsequent oxazoline ring-closure by Sn2 displacement of the resultant iodide intermediate [127]. 

Recently, Lee and co-workers reported an efficient method for the preparation of enantiomerically pure oxazolidin-2-ones from aziridine-2-carboxylates 186 (Scheme 3.68) [128]. This one-pot aziridine ring-opening and subsequent intramolecular cyclization process was highly regio- and stereoselective, affording 187 in high yield. 

S,3R)-Aziridine-2-carboxylic amide 258 (Scheme 3.95) has been used in the synthesis of the cyclic guanidino amino acid, L-epicapreomycidine (260) [145]. Treatment of 258 with saturated ammonia in methanol at 30 °C for 4 days in a pressure bottle resulted in the aziridine ring-opening product, which afforded 259 in 52 % yield after removal of the Cbz protecting group. 

It was concluded that the crosslinking reaction proceeded through initial alkylation of N-7 of adenine by the aziridine ring, followed by guanine N-7 alkylation by the epoxide (Figure 11.12). This seems inconsistent with Armstrong s earlier conclusions, but the very short oligonucleotides used by Saito et al. may influence the DNA alkylation chemistry. 

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