Asymmetric aziridination imines

Catalysts prepared either from VAPOL (109) or from VANOL (110) ligands and triphenylborate were found to catalyze the asymmetric aziridination efficiently. Good to high yields, excellent enantioselectivities, and cis diastereoselectivities were observed with all the reported substrates, which included aromatic, heteroaromatic and aliphatic imines (Table 1.14). 

Chiral dicarboxylic acid (R)-5g (5 mol%, R = Mes) bearing simpler mesityl-substituents at the 3,3 -positions was found to catalyze efficiently the trans-selective asymmetric aziridination of iV-aryl-monosubstituted diazoacetamides 177 and aromatic (V-Boc imines 11 (Scheme 75) [94], In sharp contrast to previous reports on this generally dx-selective sort of aziridination, this method exhibited unique fran -selectivity and afforded exclusively the fran -aziridines 178 in moderate to good yields along with excellent enantioselectivities (<20-71%, 89-99% ee). The 1,2-aryl shift products 179 were observed as side products in varying ratios (178 179= 56 44-90 10). Diazoacetamides were chosen instead of diazoesters. Due... 

Cycloadditions. The scope of the Evans asymmetric aziridination is broadened by the ready availability of nitrene precursor 4-02NCjH S02N=IPh. The oxazolidinone-Af-acetic acid derived from (+)-cw-2-amino-l,2-diphenylethanol participates in p-lactam formation with imines. The predominant products (>99 1) have the (3/f,45)-configuration. The intramolecular [2+2]photocycloaddition involving a chiral allenylsilane moiety is an excellent method for accessing optically active methylenecyclobutane derivatives. ... 

A screen of chiral Lewis acids was carried out by Jorgensen, but this effort failed to reveal any effective enantioselective catalysts [31]. However, very recently Wulff disclosed an extremely exciting result in the VAPOL-BH3 catalyzed reaction between ethyl diazoacetate and imines (Scheme 14) [32]. Although the details had not been published at the time this chapter was written, it seems likely that this method will constitute an important breakthrough and establish a new direction for future research in the field of asymmetric aziridination catalysis. 

Chiral cychc and acyclic allylsulfoxonium ylides are generated from sulfoxonium-substi-tuted y,8-unsaturated a-amino acids (method A) and 1-alkenylsulfoxonium salts (method B) upon treatment with DBU (1) [51] (Scheme 3.31). Their apphcation to the asymmetric aziridination of A-ferf-butylsulfonyl imine ester, generated either in situ (method A) or externally added (method B), affords the corresponding alkenylaziridinecarboxylate with medium to high diastereoselectivity and enantioselectivity. 

An alternative approach to aziridine synthesis involves transfer of a carbenoid species to imines. Jacobsen achieved the first asymmetric aziridination of imines by transfer of copper carbenoids derived from copper bis-oxazohne catalysts and ethyl diazoacetate onto imines, but this process only proceeds with moderate yield and selectivity. Better results have been achieved by addition of ethyl diazoacetate to imines in the presence of enantiopure Lewis acids such as the boron-based catalysts prepared from vaulted biaryls such as VAPOL (4.154) and B(OPh)3. A range of aryl and alkyl N-benzylaldimines, for example (4.155) and (4.156), undergo aziridination to give ds-aziridines with high ee using this procedure. 

These positive results encouraged the authors to explore the activity of the chiral dicarhojg lic acids in reactions with different nucleophiles. Interesting results were obtained with dimethyl diazomethylphosphonate (up to 96% ee) and also in the trans-selective asymmetric aziridination with diazoacetamides 66. In the latter case, the traizs-selectivity was justified by an attack on the Re face of the imine differently from the attack on the Si face observed in the addition of t-butyl diazoacetate. This opposite facial enantioselectivily was due to the preference for the rotamer with the carboxamide group and aryl group of iV-Boc-imine in an antiperiplanar orientation and in this case a hydrogen bond between the amidic NH and Boc groups acted as a secondary factor. 

A multi-component catalytic asymmetric aziridination of aldehydes employs a protected amine and ethyl diazoacetate as reactants and an (5)-VAPOL boroxinate catalyst, giving aziridine-2-carboxylic esters in up to 99% ee. It works for some cases where preformed imines failed. ... 

Asymmetric Aziridination of Alkenes. The copper-catalyzed aziridination reaction can be rendered enantioselective by the addition of chiral ligands. The first example of an enantioselective aziridination of an alkene employed the bis(oxazoline) ligand (4) (R = f-Bu) and copper(I) trifluoromethanesulfonate as the metal catalyst (eq 14). This catalyst system affords the aziridine in 97% yield and 61% ee. Other reports have appeared subsequently regarding the extended scope of this reaction. " Important contributions to this area include the copper/bis-(oxazoline)-catalyzed aziridination of aryl acrylate esters (eq 15) and the copper/bis(imine)-catalyzed aziridination of cyclic cis-alkenes with the bis(imine) ligand (5) (eqs 16 and 17). ... 

In 2004, Hossain and Redlich reported the synthesis of a series of iron-pybox complexes and their employment in the catalytic asymmetric aziridine forming reaction with imine (109a) and ethyl diazoacetate (10) (Scheme 16.31) [35]. When combined with AgSbFe, the isopropyl- and tert-butyl-pybox complexes (112a) and (112b) produce 47% of the cis-aziridine (110) in moderate enantiomeric excesses. The best overall results came when the tert-butyl pybox catalyst was used, although results obtained with the isopropyl pybox catalyst are very similar. 

Scheme 20.31 Amine-catalyzed asymmetric aziridination of an imine.

This review summarizes the best asymmetric methods for preparing epoxides and aziridines from aldehydes (or ketones) and imines. 

Asymmetric Synthesis of Epoxides and Aziridines from Aldehydes and Imines... 

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... 

Ruano has reported substrate-controlled asymmetric ylide aziridination by treatment of enantiopure sulfinyl imines 117 with dimethyloxosulfonium methylide 118 to form terminal aziridines [63], The chiral tert-butylsulfinyl group was shown... 

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

A variety of methods for the asymmetric syntheses of aziridine-2-carboxylates have been developed. They can be generally classified into eight categories based on the key ring-forming transformation and starting materials employed (i) cyclization of hydroxy amino esters, (ii) cyclization of hydroxy azido esters, (iii) cyclization of a-halo- and ot-sulfonyloxy-(3-amino esters, (iv) aziridination of ot, 3-unsaturated esters, (v) aziridination of imines, (vi) aziridination of aldehydes, (vii) 2-carboxylation of aziridines, and (viii) resolution of racemic aziridine-2-carboxylates. 

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