Aziridines chiral

Asymmetric transformation of imines into chiral aziridines remains less well developed than the analogous transformation of aldehydes into epoxides [49, 50, 51]. The reported methods can be divided into three conceptual categories involving... 

Within the biooxidation of disulfides, chiral thiosulfinates become available. Tert-Butyl tert-butanethiosulfinate represents a particularly valuable chiral auxiliary for the preparation of several chiral sulfoxides and sulfinimines, which can be subsequently transformed into branched amine compounds, P-aminoacids, and chiral aziridines. This product is accessible readily by mediated biooxidation of tert-butyl... 

During our research in this field of small-ring heterocycles we found that functionahzed aziridines are attractive chiral catalysts, e.g., in the diethylzinc addition to aldehydes. Aspects of such uses of aziridines will be discussed as well. This overview does not pretend to be an exhaustive coverage of all existing literature on small-ring aza-heterocycles as that would require a separate monograph. Instead, emphasis is put on functionahzed three-membered aza-heterocycles, that were investigated in the author s laboratory [1], and relevant related literature. The older literature on these heterocycles is adequately summarized in some extensive reviews [2]. Chiral aziridines have been reviewed recently by Tanner [3], by Osborn and Sweeney [4], and by McCoull and Davis [5]. 

In addition, these authors have developed the synthesis of chiral aziridine... 

Various approaches to epoxide also show promise for the preparation of chiral aziridines. Identification of the Cu(I) complex as the most effective catalyst for this process has raised the possibility that aziridination might share fundamental mechanistic features with olefin cyclopropanation.115 Similar to cyclo-propanation, in which the generally accepted mechanism involves a discrete Cu-carbenoid intermediate, copper-catalyzed aziridation might proceed via a discrete Cu-nitrenoid intermediate as well. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

Acromelic acid A (260), isolated from Clitocybe acromelaga, displays the most potent polarizing effect of aU known kainoids. By application of the same intramolecular aziridine thermolysis route described above, Takano et al. (80) outlined a concise entry into such compounds. Thermolysis of the chiral aziridine 261, derived from (5)-0-benzylglycidol in 1,2-dichlorobenzene at 200 °C, furnished the single reaction product 262 in 73% yield. The complete control over the... 

Chiral aziridines having the chiral moiety attached to the nitrogen atom have also been applied for diastereoselective formation of optically active pyrrolidine derivatives. In the first example, aziridines were used as precursors for azomethine ylides (90-95). Photolysis of the aziridine 57 produced the azomethine ylide 58, which was found to add smoothly to methyl acrylate (Scheme 12.20) (91,93-95). The 1,3-dipolar cycloaddition proceeded with little or no de, but this was not surprising, as the chiral center in 58 is somewhat remote from the reacting centers... 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

For reviews about the asymmetric synthesis of chiral aziridines, see (a)... 

The invertomers of the nitrogen pyramid 1-chloro-2,2-dimethylaziridine have been separated by enantioselective complexation GC on the chiral metal chelate nickel(II)-bis[(3-heptafluorobutanoyl)-( l.R>)-camphorate] (Ni-CAM2) in squalane (Schurig et al., 1979). The resolution of the chiral aziridine into two sharp peaks with a = 1.5 in 45 min at 60° C demonstrated the stereochemical integrity of the invertomers (cf. Figure 6). 

Pamies, O., and Baeckvall, J.-E. 2001. Dynamic kinetic resolution of P-azido alcohols. An efficient route to chiral aziridines and P-amino alcohols. J. Org. Chem., 66(11), 4022 1025. 

Pentamethyleneoxaziridine (6) also acts as an aminating agent, giving quite good yield of aziridines (Scheme 2). > Remarkably, none of the corresponding epoxide was reported in this reaction. Cyclohexene yields instead the hydrazino alcohol (8), probably via the V-aminoaziridine (7). In view of the recent use of chiral oxaziridines for chiral oxidations, it will be interesting to see whether chiral aziridination is possible when chiral V-unsubstituted oxaziridines become available. ... 

Chiral aziridines can be prepared by the cycloaddition of chiral trifluoromcthyl-substituted oximes with diazomethaiie. Primary cycloadducts resulting from 1,3-dipolar cycloaddition are further decomposed to provide the aziridines. ... 

Chiral sulfilimines 16 react with a./f-unsaturated carbonyl compounds in a Michael-type fashion to give chiral aziridines 17 in moderate to excellent chemical yields, but with low enantiose-lectivity. Thus, the optical purities of the isolated products are in the range 25.3 -32.6%, as calculated from the highest optical rotation obtained by repeated recrystallization of the crude... 

Acylaziridines have been stereospecifically rearranged to give oxazolines, as illustrated by the copper(ll) triflate-catalyzed conversion of the chiral aziridine 259 into (-R)-oxytriphine 260. Mechanistically, this transformation is believed to proceed via initial coordination of the amide nitrogen with the azaphilic Lewis acid. This leads to the formation of an intermediate carbocation that exists as a tight ion pair in order to preserve the stereochemistry of the rearrangement (Scheme 69) <1998JOC4568>. 

Enantiomerically pure N,N-disubstituted imidazolidine-2-one-4-carboxylates 332 can also be obtained in a one-step, simple, and highly efficient manner using a Lewis acid-catalyzed ring-expansion reaction of commercially available chiral aziridines with isocyanates. These reactions proceed both regio- and stereospecifically with retention of the configuration at the C-2 carbon of the chiral aziridines <2005CC3062>. The C(2)-N bond of the aziridine... 

Other approaches to chiral aziridines have been reported. For example, treatment of cycloheptadiene 725 with the leucine-derived (A)-3-acetoxyamino-2-(3-hydroxy-2,2-dimethylpropyl)quinazolin-4(3//)-one 724 in the presence of titanium(iv) /-butoxide (TTB) in methylene chloride leads to formation of the chiral aziridine 726, in which the chiral auxiliary (Q) is in the o-position, as the only isolated product in 29% yield (Scheme 175) <2001J(P1)1518>. 

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