Aziridine-2-carboxylic esters

Lewis acids such as zinc triflate[16] and BF3[17] have been used to effect the reaction of indole with jV-proiected aziridine-2-carboxylate esters. These alkylations by aziridines constitute a potential method for the enantioselective introduction of tryptophan side-chains in a single step. (See Chapter 13 for other methods of synthesis of tryptophans.)... 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

Darzens reactions between the chiral imine 52 and a-halo enolates 53 for the preparation of nonracemic aziridine-2-carboxylic esters 54 (Scheme 3.17) were studied by Fujisawa and co-workers [61], It is interesting to note that the lithium enolate afforded (2K,3S)-aziridirie (2i ,3S)-54 as the sole product, whereas the zinc enolate give rise to the isomer (2S,3i )-54. The a-halogen did not seem to affect the stereoselectivity. 

When aziridine-2-carboxylic ester 124 (Scheme 3.44) was treated with 1 equivalent of TFA, 125 was formed as a single diastereomer in 80% yield [57]. Use of 10 equivalents of TFA resulted in the formation of N-trifluoroacetyl product 126. This... 

In contrast to aziridine-2-carboxylic esters, treatment of aziridine lactone 166 (Scheme 3.60) with N-methylindole (167) in the presence of BF3 lil20 proceeded... 

Unlike regular aziridine-2-carboxylic esters, aziridine-2-carboxylic thioester 174 (Scheme 3.62) forms stable carbanions at the 2-position upon treatment with base [13b, 122]. Thus, electrophilic alkylations of aziridine 174 afforded products 175. The reactions were highly diastereoselective, affording 175 in moderate to good... 

Treatment of aziridine-2-carboxylic ester 251 (Scheme 3.93) with benzyl mercaptan in the presence of boron trifluoride etherate afforded 252 in 71% yield [142]. Compound 252 has been transformed into peptide 253, an analogue of a penicillin precursor. 

FR900490 (264 Scheme 3.96), a new immunomodulator, has been prepared from aziridine-2-carboxylic ester 261 [146, 147]. This aziridine reacts with (S)-histi-dine (262) in the presence of 1 n sodium hydroxide, giving 263 in 31-44% yield... 

Cycloaddition reactions of aziridine-2-carboxylic esters have also been used... 

Keywords Aziridine-2-carboxylic esters. Ring expansion reactions, Azirine carboxylic esters, Aziridine carbinols. Anomalous amino acids... 

Anomalous Amino Acids from Aziridine-2-carboxylic Esters. 105... 

An attractive and useful method for the preparation of aziridine-2-carboxylic esters makes use of the readily available amino acids serine and threonine. Essentially, this synthesis involves the ring closure of 1,2-amino alcohols. 

The first compound is an antibiotic isolated from Streptomyces aureus [20], while the second compound is a cytotoxic antibiotic isolated from Dysidea fragilis, a marine sponge [21]. A logical approach to the synthesis of azirines would be an elimination reaction of a suitably M-substituted aziridine. Thus, AT-chlorination of aziridine-2-carboxylic esters was carried out using ferf-butyl hypochlorite (Scheme 8). 

Enantiopure a-amino aldehydes are valuable synthons in natural product synthesis [57]. However, problems are often encountered with their configurational instability [58]. Aziridine-2-carboxaldehydes are also a-amino aldehydes and accordingly have a potential synthetic value. We found that M-tritylaziridine-2-carboxaldehyde 56 is a perfectly stable compound and therefore comparable to Garner s aldehyde (ferf-butyl 2,2-dimethyl-4-(S)-formyl-oxazolidine-3-car-boxylate). Aldehyde 56 can readily be prepared from aziridine-2-carboxylic ester 12 by the sequence shown in Scheme 42 [59]. 

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

Zwanenburg and coworkers14 reported that aziridine-2-carboxylic esters (1) when treated with -butyl hypochlorite give Y-chloroaziridines (2) (equation 4). Referring to... 

By analogy with cyclopropanes and oxiranes, 2-acylaziridines, aziridine-2-carboxylic esters and amides, are also suitable substrates for one-electron reductive ring cleavage. This is an efficient and highly regioselective method for the synthesis of yS-amino carbonyl compounds. Vinylogous substrates are, furthermore, transformed into <5-amino y8,y-unsaturated carbonyl derivatives azetidines can also be used to achieve y-amino functionalization (Scheme 19) [72]. 

Davis, F. A., Liu, H., Zhou, P., Fang, T., Reddy, G. V., Zhang, Y. Aza-Darzens asymmetric synthesis of N-(p-toluenesulfinyl)aziridine 2-carboxylate esters from sulfinimines (N-sulfinyl imines). J. Org. Chem. 1999, 64, 7559-7567. 

Aziridines. Aziridine-2-carboxylic esters are formed at room temperature by reaction of conjugated esters with NsONHCOOEt in the presence of CaO. Similarly, nitroalkenes react in the same way.- ... 

Cleavage of aziridines. Aziridine-2-carboxylic esters undergo ring opening to... 

Adridines. A synthesis of aziridine-2-carboxylic esters by the reaction of hexahydro-l,3,5-triazines with alkyl diazoacetates in the presence of SnCl is subject to asymmetric induction by a chiral substituent attached to the nitrogen atom. ... 

An optically pure cyclic analogue of aziridine-2-carboxylate ester was prepared from ribose via a Ph3P-promoted conversion of 3-azido-2-tosyl-D-xylofuranoside to its corresponding 2,3-aziridine (95) (Scheme 34) <93T90l>. The procedure is directly applicable to the synthesis of enantiomerically pure 2,3-aziridine carboxylate isomers from D-lyxose. 

Guanidinium ylide 132 generated in situ reacts with aldehydes to give aziridine-2-carboxylic esters (cis/trans isomer mixtures). Chiral information located four bonds away is transmitted and it guides the alignment of the reactants. 

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