Stereochemistry of aziridines

Aziridination of trans- and cis- 8-methylstyrene with benzy-lainine gave two diastereomeric aziridines with almost the same yields and diastereomeric ratio (1 1), suggesting that the stereochemistry of aziridines is not influenced by the olefin configuration. A one step protocol can also be appUed in case of unstable 2-arylethenyl(diphenyl)sulfonium salts. 

The stereochemistry of aziridine ring substitution, as pointed out above, is controlled by the product distribution in the p-amino-a-bromoketone intermediate, which in this case favors the erythro configuration. Thus, inversion of configuration during ring formation leads to the trans-substituted aziridine... 

Aroylaziridines (32) and aromatic aldehydes react to give oxazolidines (33), the stereochemistry of which suggests reaction very largely through the trans-azomethine ylide, irrespective of the aziridine configuration (70JCS(C)2383). 

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

More recently, Tardella and co-workers reported that treatment of 2-trifluorome-thyl acrylate 36 (Scheme 3.12) with the anion generated from nosyloxycarbamate 37 gave rise to aziridine-2-carboxylate 38 in 96% yield and 72% de with undetermined stereochemistry [40]. Aza-MIRC (Michael-initiated ring closure) was used to account for this transformation. A number of other hydroxylamine derivatives have been employed successfully in this type of aziridination reaction, includ-... 

Madurastatins A1 (119 Scheme 11.17), A2 (120), A3 (121), B1 (122), and B2 (123) were isolated in 2004 from a clinical isolate of a pathogenic actinomycete, a strain of Actinomadura madurae [189]. The stereochemistry of the N-methyl-N-hydrox-yornithine residue remains unknown, but it was determined that the serine and aziridine residues are D, and the rest are L. 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Another problem with the reaction of phenols with aziridines is the selectivity between O-alkylation vs C-alkylation. A recent report has identified that the use of (ArO)3B selects for C-alkylation <06OL2627>. Most of the examples reported in this paper showed less than 5% of the O-alkylation product. What is interesting about this report is the stereochemistry of the product. While the mechanism is not known, the product is formally an SNl type product. Generally less than 5% was the product of inversion of configuration (the Sn2 product). In addition to the A-tosyl, both the A-Cbz and A-Dpp aziridines gave excellent yields of aziridine-opened product. 

In the reaction of fused aziridines with alkene dipolarophiles, the opportunity for stereoselectivity as well as facial selectivity arises since exo- or entfo-isomers can be formed (Scheme 10). In practice, maleic anhydride 6, A-methyl maleimide and JV-phenyl maleimide each reacted exo-stereoselectively with TV-benzyl aziridine 69 to form adducts of type 71 (Scheme 10b), the stereochemistries of which were confirmed by NOE measurement between Hb and He. Similar reaction of the Y-phenyl aziridine 67 with N-Ph maleimide gave a 1 1 mixture of endo-adduct 72 and exo-adduct 73 (Scheme 10c). Adducts 68, 71-73 all exhibited a low-field methano-bridge proton (Ha) in the range 5 3.06-3.60 confirming the syn-facial stereochemistry of the two bridges. 

Likewise Bi(OTf)3 catalyzes the reaction of aziridines to give the corresponding (3-amino alcohols (Fig. 8). In the case of cycloalkyl aziridines, the stereochemistry of the ring-opened products was found to be trans. This method has some additional features of green aspects as it allows the recovery and re-usability of the catalyst. 

At about the same time, Wenkert and c-workers (75) reported a similar smdy into the intramolecular 1,3-dipolar cycloaddition of 2-alkenoyl-aziridine derived azomethine ylides. Thermolysis of 231 at moderate temperature (85 °C) produced 232 as a single isomer in 58% yield. Similarly, 233 furnished 234 in 67% yield. In each case, the same stereoisomers were produced regardless of the initial stereochemistry of the initial aziridine precursors. However, the reaction proved to be sensitive to both the substituents of the aziridine and tether length, as aziridines 235 and 236 furnished no cycloadducts, even at 200 °C (Scheme 3.79). 

Phenylindolone (158 R = Ph) also reacts with other 1,3-dipolar molecules. A-er-Diphenylnitrone14 and cis- and frans-aziridines 193134.13s form tjje expected adducts (194, 195).49 The stereochemistry of 195 has not yet been eluciated. 2-Phenylisatogen does not react with 2-phenylindolone under these conditions the starting materials were recovered.49... 

In marked contrast to this behaviour, monomer 11, l-benzyl-2-methyl-aziridine, gives a relatively slow reaction with Et30+BF4. However, polymerisation is quantitative and all the indications are that the system is living . Why this would be so is difficult to explain. Electronic factors would seem to be elimi-minated since this monomer is intermediate as far as basicity is concerned. Presumably the explanation lies in the stereochemistry of the system since this particular monomer is the only carbon substituted species. Even more strangely, however, the closely related molecule l-benzyl-2-ethyl-aziridine is reported (141) to behave like 8,9, and 10 when treated with boron trifluoride. 

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