Bis-aziridines

The stereoselectivity established for the trident series, was tested using the C-bridged bis-aziridine 58 which produced the ONCNO-[5]polynorbomane 115 by reaction with the O-bridged dipolarophile 36 (two equivalents) in 70% yield (Scheme 19). However, as noted above, replacing the central C-bridge with the A-Z bridge caused loss in stereoselectivity. Accordingly the type B approach was preferred. 

Tanner et al. (58) investigated the use of chelating diaziridines (85) as ligands for transition metals. The cyclopropanation of styrene using CuOTf complexes of phenyl-substituted aziridine (85a) proceeds in modest enantioselectivity and dias-tereoselectivity, but improved enantioselectivity is observed with complexes derived from benzyl-substituted bis(aziridine) (85b), Eq. 42 (59). Complexes derived... 

Tanner et al. (58) investigated the asymmetric aziridination of styrene using bis(aziridines) such as 85. Low induction is observed with these ligands, Eq. 64. A significant electronic effect was noted with the p-fluoro-phenyl substituted bis(az-iridine) 85c (59). A binaphthyl-derived diamine was used as a ligand for the copper-catalyzed aziridination of dihydronaphthalene (81). The product was formed in 21% ee and 40% yield, Eq. 65. Other structurally related ligands proved to be less selective in this reaction. 

Enantiomeric excesses of up to 76% have been obtained for alkyllithium-aldehyde condensations using 3-aminopyrrolidine lithium amides as chiral auxiliaries. Addition of organolithiums to imines has been achieved with up to 89% ee, in the presence of C2-symmetric bis(aziridine) ligands. ... 

Bis-aziridines (2), activated by electron-withdrawing substituents on the nitrogen atoms, behave in a similar way (60GEP1081169). The activating group is important with regard to stability of the hardener and to its reactivity with the protein chains. 

N2CHC02Et, cat CuOTf-OJCeHs N2CHC02Et, cat CuOTf or Cu(OTf)2, cat bis(aziridine) (enantioselective)... 

Reaction of 13 [R2 = C(4-CFl3OC6H4)(C6H5)2] with 1,3-diaminopropanc, however, takes a slightly different course in that the major product isolated is the 2, 3 -[A/-(3-aminopropyl)]-ribo-aziridine 22 (76%) along with a bis-aziridine dimer 23 (21 %)106. The reaction of 13 (R2 = H) with 1,3-diaminopropane gives only the a-aziridine nucleoside 22 (76%) with no trace of a dimer. 

Addition to C=N. Imine derivatives which contain a chirality center adjacent to, or one atom away from the nitrogen atom are attacked by nucleophiles enantioselectively. Examples include p-toluenesulfinimines " and 42, 43, and 447 Reaction of lithium ester enolates with imines in the presence of the Cj-symmetric dimethoxybibenzyl leads to P-lactams in good ee, and a bis(aziridine) ligand is useful for enantioselective addition of RLi to imines. ... 

As part of an ongoing research program directed toward the use of chiral aziridines in asymmetric synthesis [36], Andersson, Tanner and co-workers have recently reported the detailed results of their own findings in the field of catalytic asymmetric dialkylzinc alkylation of imines [37dj. Tanner et al. had previously communicated their success in the catalytic asymmetric addition of organolith-ium reagents to imines with C2-symmetric bis(aziridines) [37a, 37b]. This was followed by a preliminary report on the use of aziridino alcohols as well as simple aziridines for the addition of diethylzinc to M-diphenylphosphinoylimines [37c]. The most recent report is an extension of this study, and includes the detailed preparation of the ligands [37d]. 

Some aziridine (or bis-aziridine) by-product, formed by a 1,3-displacement of the tosylate by the amine group, was observed in the NMR spectrum, but it was not separated. Other diaza-crowns, including those from unsymmetric starting diazadiols, have been prepared with yields of up to 30% (Ajinomoto,... 

A synthesis of 3 starting from a conformationally flexible D-mannitol A-Boc bis-aziridine derivative 81 has been reported (Scheme 14). The cyclic carbamate-protected pyrrolidine 82 was obtained from 81 via the regioselective bis-aziridine ring opening with Li2NiBr4, followed by Ag+-promoted intramolecular substitution of the bromide by the N -Boc group in 75% overall yield. Nitrous acid deamination of 82 with isoamyl nitrite led, in 50% yield, to a 1 1 mixture of cyclic carbamate protected pyrrolidines 84 and 85 via the intermediate... 

Scheme 4 shows a novel route to 2-thiosophorose (51) which equilibrates readily with 2-thioepisophorose (52). Preparation of diheterodisaccharide 53 and related glycosidase inhibitors involved opening of bis-aziridine 54 with l,2 5,6-di-0-isopropylidene-3-thio-a-D-glucofuranose. ... 

The well known, D-mannitol-derived bis-aziridine 37 has been used to prepare 6-amino-6-deoxy-2,5-imino-D-glucitol and -1,5-imino-D-mannitol derivatives 38 and 39 as potential glycosidase inhibitors. Treatment of 37 with acetic add, or alternatively allyl alcohol in the presence of an ytterbium catalyst, afforded mono-O-acetylated or -allylated glucitol/mannitol mixtures in 2 1 and 1 2 ratios respectively. ... 

Fused-ring and Bicyclic Azasugars. - Four new polyhydroxypyr-rolizidines, the Hyacinthacines Ai, A2, A3 and B3 (118-121 respectively) were isolated from the bulbs of Muscari armeniacum, and their structures elucidated. Bis-aziridine 37 (see Section 1.3.1), derived from D-mannitol, was converted... 

Some peculiar observations were made when the model carbanion of chloromethyl phenyl sulfone was reacted with quinoxaline (Scheme 11) [65]. Instead of the expected VNS product, the bis-aziridine derivative was formed. 

Reaction of the L-idb-bis aziridine 51 with sodium azide and tetrabutylammonium iodide affords the pyrrolidine 52, whereas reaction of 51 with thiophenol and sodium hydroxide affords pyrrolidine... 

Certain arachidonate aziridines such as 13-(3-pentyl-2-aziridinyl)-5,8,11-trideca-trienoic acid (104) and its methyl ester (105) have been synthesized [123] which are inhibitors of arachidonate epoxygenase [124]. Preparation of the fatty acid aziridines (106-115) has been described [125]. Bis(aziridine) Me cis-9,10 cw-12,13-diepiminooctadecanoate, derived from hnoleic acid, and tris (aziridine) and Me c /s-9,10 c/s-12,13 cfr-15,16-triepimino-octadecanoate, both derived from linolenic acid, showed cytotoxic and antimicrobial activity as well as remarkable antitumor-promoting and useful neuroprotective effects [126]. 

Earlier work on the s mthesis of chiral a-hydroxyaldehydes (see Vol. 21, p. 174 and Vol. 20, p.270) from d-mannitol-derived diepoxides has been extended to the synthesis of methyl (i )- and (S)-9-hydroxyeicosatetraenoates (methyl 9R-and 9S-HETE), and to coriolic acid [13(S)-hydroxy-9Z,llE-octadecadienoic acid] and its 13(S)-N-tosylamino-analogue. made from a bis-aziridine (Vol. 20, p.271). 8... 

These resins were prepared by the method as described by Manecke and Heller based on the copolymerization of a bis-aziridine with a monofunctional one [16], namely 1,4-bis (j3-propyleniminoethyl)benzene and methyl l-(2-methylaziridinyl)acetate, in a molar ratio 0.18 to 0.27, in the presence of diethylsulfate as catalyst. The scheme of the reaction is as follows ... 

As mentioned in the experimental part, these resins were synthesized by copolymerization of a bis-aziridine with methyl l-(2-methylaziridinyl)acetate. The resins were saponified, transformed into their amphoteric ionic form, and sieved in order to obtain particle sizes with a diameter 0.25—0.50 mm adequate for the complexation experiments. These resins permit the determination of the ionic binding capacity of PPG i.e. the ratio of the number of actually bound metal ions to the theoretical number, based on the analytical composition of the resins and assuming a coordination number four. 

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