Aziridination asymmetric

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). 

Table 1.16 Chiral tert-butylsulfinylimines in asymmetric aziridine synthesis.

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. 

In 1995, aziridination with 1,3-dienes 10 by treatment with PhI=NTs 9 was developed (Scheme 2.4) [10] on the foundation of pioneering works by Jacobsen and Evans on copper-catalyzed asymmetric aziridination of isolated alkenes [11]. 

Scheme 2.5) was recently reported by Komatsu, Minakata, and coworkers [12]. The reaction with the (i ,i )-complex 12 provided the first reagent-controlled asymmetric aziridination of conjugated dienes, although enantioselectivities were only low to moderate (20-40% ee). 

Asymmetric aziridination of a,P-unsaturated esters by use of N-nitrenes was studied in great detail by Atkinson and co-workers [34, 35]. Here, lead tetraacetate-mediated oxidative addition of N-aminoquinazolone 30 (Scheme 3.10) to a-methy-lene-y-butyrolactone 32 was reported to proceed with complete asymmetric indue-... 

Aziridines were amongst the first heterocycles to be prepared by synthesis, and they occupy a special place in organic synthesis. This chapter has, we hope, indicated the rich chemistry associated with this area of synthetic endeavor in both the distant and the recent past it is clear that the recent exciting developments in asymmetric aziridine synthesis indicate a most promising future for the practitioners in the field and the greater synthetic community at large. 

Jacobsen et al. reported that a different type of dintrogen ligand (48), fe[(2,6-dichlorophenyl)-methylideneaminojcyclohexane, was an efficient chiral ligand for copper-mediated asymmetric aziridination (Scheme 35).154 The reactions of conjugated c/.v-olefins show high enantioselectivity with this catalyst, but enantioselectivity of the reactions of simple olefins such as styrene and indene is moderate. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Both compounds were tested for their catalytic activity in asymmetric aziridination using p-toluenesullbnic anhydride (TS2O) to activate the nitridomanganese complex. As shown in Scheme 4-60, the aziridination generally gave poor results, while addition of pyridine A-oxide improved both the yield and the enantiomeric excess of the products. 

Jacobsen and co-workers (61) demonstrated that diimine-copper complexes are moderately selective for the asymmetric cyclopropanation of 1,2-dihydro-naphthalene, Eq. 44. A correlation was found between selectivities in the asymmetric aziridination and the asymmetric cyclopropanation catalyzed by the same species. Jacobsen argues that this supports the notion that the two processes follow similar mechanistic pathways. These workers also studied the complexation event between alkenes and Cu(I)-diimine complexes by NMR and by crystallographic characterization (62). For a thorough treatment of these results, see Section II.B.3. 

A number of other bis(oxazolines) have been applied as ligands in the copper-catalyzed aziridination reaction. Knight and co-workers (80) examined tartrate-derived ligands. Diastereomeric bis(oxazolines) 110 and 111 were each found to be poorly effective in mediating the asymmetric aziridination of styrene, Eq. 63. 

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. 

In a study published concurrently with the Evans bis(oxazoline) results, Jacobsen and co-workers (82) demonstrated that diimine complexes of Cu(I) are effective catalysts for the asymmetric aziridination of cis alkenes, Eq. 66. These authors found that salen-Cu [salen = bis(salicylidene)ethylenediamine] complexes such as 88b Cu are ineffective in the aziridination reaction, in spite of the success of these ligands in oxo-transfer reactions. Alkylation of the aryloxides provided catalysts that exhibit good selectivities but no turnover. The optimal catalyst was found to involve ligands that were capable only of bidentate coordination to copper. 

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. 

Benzylidene derivatives of the enantiomers of 1,2-diaminocyclohexane are also excellent ligands for the Cu(I)-catalyzcd asymmetric aziridination of olefins with 64, but the enantioselectivities using acyclic alkenes were about the same as those using ligand (S, S )-6658. When (5, 5 )-bis-(2,4-dichlorobenzylidenediamino)cyclohexane [(S,S)-67] was employed with C.u(I) triflate, 6-cyano-2,2-dimethylchromene (68) was converted to (R,R) 69 in a 75% yield with an ee greater than 98%58. 

A chiral D4-manganese(III) porphyrin catalyst, Mn(P )(MeOH)(OH) [H2P = 5, 10, 15,20-tetrakis(l,2,3,4,5,6,7,8-octahydro-l,4 5,8-dimethanoanthracene-9-yl)porphyrin], has been shown to catalyse the asymmetric aziridination of substituted styrenes (105) with enantiomeric excess of 43-68% (Scheme 40). ... 

There have also been significant advances in the imido chemistry of ruthenium and osmium. A variety of imido complexes in oxidation states +8 to +6 have been reported. Notably, osmium (VIII) imido complexes are active intermediates in osmium-catalyzed asymmetric aminohydroxyl-ations of alkenes. Ruthenium(VI) imido complexes with porphyrin ligands can effect stoichiometric and catalytic aziridination of alkenes. With chiral porphyrins, asymmetric aziridination of alkenes has also been achieved. Some of these imido species may also serve as models for biological processes. An imido species has been postulated as an intermediate in the nitrite reductase cycle. " ... 

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... 

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