Catalytic Asymmetric Aziridination

Aryl, Vinyl, and Alkyl Aziridines Catalytic Asymmetric Ylide-mediated Aziridination... 

Catalytic asymmetric epoxidation and aziridination mediated by sulfur ylides 98SL329. 

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]. 

Table 1.17 Catalytic asymmetric ylide-mediated aziridination.

Aziridination remains less well developed than epoxidation. Nevertheless, high selectivity in inline aziridination has been achieved through the use of chiral sulfi-nimines as auxiliaries. Highly successful catalytic asymmetric aziridination reactions employing either sulfur ylides or diazo esters and chiral Lewis acids have been developed, although their scope and potential applications in synthesis have yet to be established. 

The first catalytic, asymmetric aziridination of an alkene in good yield and high enantioselectivity was recently reported56. Thus styrene (63) was treated with [N-(p-toluenesulphonyl)imino]phenyliodinane (64) and an asymmetric copper catalyst to yield (/ )-Ar-(p-toluenesulphonyl)-2-phenylaziridine [(/ )-65] in 97% yield with an ee of 61%, the catalyst being the complex formed in situ in chloroform from the chiral bis[(5 ) 4-ferf-butyloxazoline] [(S,S)-66] and copper triflate (CuOTf)56, the reaction proceeding by way of a nitrene transfer57. 

Similar catalytic asymmetric approach has been successfully used in the reaction of a sulfonium ylide with electron-deficient imines" " and alkenes," " giving aziridines 135 and cyclopropane 136 with high enantioselectivity, respectively (Scheme 15). 

In this chapter, the recent development of catalytic asymmetric epoxidation and aziridination of simple olefins bearing no pre-coordinating substituent is discussed. 

Like epoxides, chiral non-racemic aziridines are useful synthetic intermediates [3, 71], and a number of methodologies have been developed for their asymmetric synthesis [3, 6, 14, 72, 73]. Although several groups have developed stoichiometric methods using chiral ylides [16, 20, 22, 74, 75], catalytic asymmetric ylide azir-idinations remain relatively rare. In fact, the first catalytic aziridination with an ylide was only reported ten years ago [76]. Progress in this area is reviewed in the following section. 

Scheme 10.18 Catalytic asymmetric aziridination via alkylation of sulfide 24 and deprotonation.

In addition to epoxides, three-membered nitrogen heterocycles, aziridines, can be obtained by means of catalytic asymmetric aziridinations (Eq. 30). To this aim, chiral ruthenium(salen) complexes 67 [56] and 68 [57] were useful (Fig. 1). The former phosphine complexes 67 gave the aziridine from two cy-cloalkenes with 19-83% ee [56]. On the other hand, terminal alkenes selectively underwent aziridination in the presence of the latter carbonyl complex 68 with 87-95% ee [57]. In these examples, N-tosyliminophenyliodinane or N-tosyl azide were used as nitrene sources. Quite recently, catalytic intramolecular ami-dation of saturated C-H bonds was achieved by the use of a ruthenium(por-phyrin) complex (Eq. 31) [58]. In the presence of the ruthenium catalyst and 2 equiv iodosobenzene diacetate, sulfamate esters 69 were converted into cyclic sulfamidates 70 in moderate-to-good yields. 

Asymmetric aziridination can also be accomplished via chiral salen ligands. Shi has synthesized a number of axially dissymmetric binaphthyldiimine salen complexes that have shown excellent facility in catalytic asymmetric aziridination reactions <2001TA3105>. Although yields were generally good with acyclic electron-deficient olefins, the chemical yield with electron-rich olefin indene was relatively low (25%). A reasonable enantiomeric excess of 73% was achieved at —20°C over a 24h reaction period (Equation 9). 

AggarwaU, V. K. Catalytic Asymmetric Epoxidation and Aziridination Mediated by Sulfur Ylides. Evolution of a Project, Synlett 1998, 329-336. 

Miscellaneous. There are several other reports on the application of this ligand to catalytic asymmetric reactions, although enantioselectivities are modest. Those reports include the Mukaiyama-Michael reaction, allylation of aldehydes, asymmetric Diels-Alder reaction, Mukaiyama-Aldol reaction of ketomalonate, aziridination reaction of a-imino esters, and asymmetric hetero-Diels-Alder reaction. ... 

Muller P, Fruit C. Enantioselective catalytic aziridinations and asymmetric nitrene insertions into CH bonds. Chem. Rev. 2003 103 2905-2919. 

Aggarwal VK, Winn CL. Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds scope, selectivity, and applications in synthesis. Acc. Chem. Res. 2004 37 611-620. Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97 2341-2372. 

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]. 

Muller, P. (2003) Catalytic enantioselective aziridinations and asymmetric nitrene insertions. Chem. Rev., 103, 2905. 

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. 

Scheme 11.36 First three-component catalytic, asymmetric, aziridination reaction [55],...

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. ... 

Catalytic Nitrene Transfer to Heteroatoms. The experimental procedure described above for the copper-catalyzed aziridination of olefins can be applied to the imidation of sulfides, where CuOTf in conjunction with PhI=NTs mediates the formation of siilfimides in good yields (eq 95). Spontaneous [2,3] sigma-tropic rearrangements occur in the case of allylic sulfides. Chiral bis(oxazoline)-CuOTf complexes catalyze both reactions with acceptable enantioselectivities (eq 96). Chloratnine-T is also a suitable but less efficient nitrene precursor. Selenides undergo the same catalytic asymmetric imidation to afford selenimides albeit with lower yields and enantioselectivities. ... 

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. 

Aggarwal, V. K., Alonso, E., Fang, G., Ferrara, M., Hynd, G., Porcelloni, M. (2001). Application of chiral sulfides to catalytic asymmetric aziridination and cyclopropanation with in situ generation of the diazo compound. Angewandte Chemie - International Edition, 40, 1433-1436. 

Scheme 6.14 Catalytic asymmetric aziridination using chiral diimine ligands ...

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