Aziridine-2-carboxylic esters, reactions

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. 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

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... 

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... 

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). 

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. 

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.- ... 

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. ... 

J. Legters, J. G. H. Willems, L. Thijs, and B. Zwanenburg, Synthesis of functionalized amino acids by ring-opening reactions of aliphatically substituted aziridine-2-carboxylic esters. Reel. Trav. Chim. Pays-Bas-J. Roy. Neth. Chem. Soc., Ill (1992) 59-68. 

In 2011, WulfTdescribed the first three-component catalytic asymmetric aziridi-nation reaction of an aldehyde 92, bis(dimethylanisyl)methylamine (163), and ethyl diazoacetate (164) to provide the corresponding chiral aziridine-2-carboxylic esters (165) [55]. When promoted by a chiral boroxinate catalyst in situ generated from B(OPh)3 and chiral Hgand (S)-VAPOL (2,2 -diphenyl-(4-biphenanthrol)), the reaction afforded products 165 with good yields and excellent diastereoselectivities and enantioselectivities (Scheme 11.36). This novel methodology furnished an effective solution to the problem of unstable imines derived from aliphatic aldehydes that cannot be purified. 

Aziridine carboxylates are chiral intermediates for the synthesis of -lactams and amino acids [200]. The use of enantioselective ester hydrolysis in the synthesis of optically active A -unsubstituted and A-substituted aziridine carboxylate by Candida cylindraceae lipase has been demonstrated by Bucciareli et al. [199]. Racemic methyl aziridine-2-car-boxylate and 2,3-dicarboxylate 110 were used as substrates both for enzymatic hydrolysis and for the synthesis of AAchloro, iV-acyl and A-sulfonyl derivatives (Fig. 38). The reaction yield of 35-45% (theoretical maximum yield is 50%) and the e.e. s of 90-98% were obtained depending on substrate used in the reaction mixture. 

A general method for the synthesis of N-unsubstituted aziridine-2-carboxylates involves a triphenylphosphine-mediated reductive cyclization of hydroxy azido esters [17-22]. A recent example involves the treatment of [1-hydroxy-a-azido ester 15 (Scheme 3.6) with PPh3 to give aziridine 16 in 90% yield [19]. a-Hydroxy- 3-azido esters undergo similar reactions to give aziridine-2-carboxylates [20-22],... 

The BF3 Et20-catalyzed aziridination of compounds 47 (Scheme 3.15) with a diazo ester derived from (R)-pantolacetone gave aziridine-2-carboxylates 48 [59]. The reaction exhibited both high cis selectivity (>95 <5) and excellent diastereose-lectivity. Treatment of a-amino nitrile 49 (Scheme 3.16) with ethyl diazoacetate in the presence of 0.5 equivalent of SnCl4 afforded aziridines 50 and 51 in 39% yield in a ratio of 75 25 [60]. 

Ring-opening of aziridine-2-carboxylates with alcohols has been reported to give (3-alkoxy-a-amino esters [16, 102]. Treatment of as-aziridine 127 (Scheme 3.45) with alcohol in the presence of a catalytic amount of boron trifluoride etherate afforded P-alkoxy-ot-amino esters 128 in 57-100% yields [16,102a], The reaction is both regio- and stereoselective, affording 128 as the only product. 

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