Copper-catalyzed aziridination of olefins

The transition metal-mediated nitrenoid transfer to olefins represents a very concise route to the aziridine structure very often, however, an excess of the olefinic substrate is required for preparatively useful yields. In this arena, Andersson and co-workers have studied the copper-catalyzed aziridination of olefins using [A -(arenesulfonyl)imino]phenyliodinanes 446 as nitrene precursors, and have reported on conditions which give good to excellent yields of aziridines 447 without the constraint of having to use an excess of alkene (Scheme 116). 

NTs [17,18]. Simple copper(I) and copper(II) salts were found to be effective catalysts for the preparation of a wide range of racemic aziridines (Scheme 7). More recently, rhodium-based catalysts have been applied with success to the reaction of PhI=NNs with alkenes [19]. Along with Sharpless s recently-disclosed brom-onium ion-catalyzed reaction [3], the copper-catalyzed aziridination of olefins with PhI=NTs is probably the most general catalytic method devised thus far for the direct synthesis of racemic aziridines from alkenes. 

The reaction is proposed to proceed via an intermediary copper nitrenoid species as known from the related copper-catalyzed aziridination of olefins [54]. A tentative transition state model for the stereochemical outcome of the oxidation ofp-tolyl methyl sulfide was suggested in which the approach of the sulfide was directed by a n-K interaction between the phenyl ring of ligand 30 and the aryl group of the sulfide. However, to date the exact mechanism remains unclear. 

Imidoiodane 466 [PhINSes, where Ses = (trimethylsilyl)ethanesulfonyl] was prepared by a similar procedure from (diacetoxyiodo)benzene and the respective sulfonamide [631], This reagent is useful for the copper-catalyzed aziridination of olefins leading to the synthetically versatile Ses-protected aziridines. 

Earlier developments of the copper-catalyzed aziridination of olefins have been hmited to the use of PhI=NTs. In order to enhance the efficiency and the scope of the process, other iminoiodanes have been described. CuOTf thus mediates the formation of A-(Ses)aziridines starting from -[2-(trimethylsilyl)ethanesulfonyl]imino phenyliodane (eq 88). CuOTf also catalyzes the intramolecular aziridination of olefins from unsaturated iminoiodanes, allowing access to substituted cyclic sulfonamides (eq 89). More interestingly, the copper-catalyzed aziridination can be performed directly from the corre-... 

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. ... 

Aziridines, the smallest heterocycles, are an important class of compounds in organic chemistry. Interesting access [8] to aziridines by using Bromamine-T as a source of nitrogen in the copper (Il)-catalyzed aziridination of olefins in MeCN was recently reported. Application of microwaves has resulted in enhanced yields for aziridines [9] with short reaction times (Scheme 8.5). 

Jacobsen and co-workers have reported that chiral diimine 33a serves as an effective chiral auxiliary for the copper-catalyzed aziridination of aryl-substituted Z-olefins (Scheme 6B.35) [80], For example, the aziridination of 6-cyanochromene proceeds with high enantioselectivity (>98% ee). Comparison of ligands 33a-33c has revealed that the o-substituents in the ligands sterically and electronically influence the enantioselectivity of the reaction, that is, the introduction of chlorines at o-positions not only prolongs catalyst lifetime but also enhances enantioselectivity. The reactions of other Z-substrates and cinnamate esters catalyzed by 33a show moderate-to-high enantioselectivity, whereas that of -stilbene gave low enantioselectivity (Table 6B.3). 

Significant recent interest in the transition metal catalyzed reactions of imidoiodanes was initiated in the 1990s by the pioneering works of Evans [586, 763, 764] and Jacobsen [765,766] on the asymmetric aziridination of olefins using copper catalysts (2-10 mol%) with chiral dinitrogen ligands and PhD JTs as the nitrene precursor. Since these initial publications, research activity in this area has surged and the copper-catalyzed aziridination of alkenes has been utilized in numerous syntheses. For example, Dodd and coworkers applied the Evans aziridination procedure to 2-substituted acrylates and cinnamates 649 [767] and to steroids 650 (Scheme 3.257) [768]. 

The copper-catalyzed aziridination of the appropriate olefinic substrates has been employed in the preparation of various 2-acylaziridines [769,770] and aziridinylphosphonates 651 (Scheme 3.258) [771],... 

An interesting application of copper-catalyzed aziridination is the preparation of ( )-olefin dipeptide isosteres based on a diastereoselective nitrene transfer onto chiral ( )-crotylsilanes (eq 86)7 CuOTf catalyzes the formation of an aziridine whose rearrangement after spontaneous desilylation affords allylamines. Excellent levels of acyclic stereocontrol can be achieved via a hydroxyl-assisted aziridination. Copper-catalyzed aziridination of enol ethers also leads to aziridines that undergo spontaneous rearrangement. Thus, CuOTf and particularly CUCIO4 mediate the formation of an a-methylserinal derivative from a 5-methyl-4//-1,3-dioxin (eq 87). ... 

The direct copper-catalyzed iodosyl-mediated nitrogen transfer to olefins compares with the parent rhodium-catalyzed process that is made possible by the combination of iodosylbenzene diacetate, magnesium oxide, and sulfamates. Other recent promising nitrene transfer methods involve the bromine-catalyzed aziridination of olefins using chloramine-T and the direct electrochemical aziridination with TV aminophthalimide. ... 

Addition of carbethoxynitrenes to olefinic double bonds occurs readily. Addition of both the singlet and the triplet species can take place, the former stereospecifically, the latter not 49>. Additions of sulphonyl nitrenes to double bonds have not been demonstrated except in two instances in which metals were present. The reason is that either addition of the starting sulphonyl azide to the double bond occurs to give a triazoline that loses nitrogen and yields the same aziridine as would have been obtained by the direct addition of the nitrene to the olefin, or the double bond participates in the nitrogen elimination and a free nitrene is never involved 68>. The copper-catalyzed decomposition of benzenesulphonyl azide in cyclohexene did give the aziridine 56 (15%), which was formulated as an attack by the sulphonyl nitrene-copper complex on the double bond 24>. 

The first metal-catalyzed nitrogen atom-transfer process was reported by Kwart and Khan, who demonstrated that copper powder promoted the decomposition of benzenesulfonyl azide when heated in cyclohexene.280 Evans has demonstrated that Cu(i) and Cu(n) triflate and perchlorate salts are efficient catalysts for the aziridination of olefins employing TsN=IPh as the nitrene precursor.281 Subsequent to this finding, intensive effort has focused on the identification of... 

Copper complexes catalyze formally related aziridination of olefins with ]7V-(p-toluenesulfonyl)imino]phenyliodinane, a nitrene precursor (219b). As exemplified in Scheme 98, catalysts formed from Cu(I) tri-flate and optically active bis(oxazolines) effect enantioselective reaction of styrene (Scheme 98) (218b, 219a). 

Evans et al. proposed that an imino-copper species in the 3+ oxidation state (Cu3+=NTs) should be the key intermediate in copper-catalyzed aziridinations [75b]. This proposal was supported by Jacobsen s study on the dependence of enantioselectivity on the nitrene precursors and/or the substrate structures with two iminoiodoarenes, PhI=NTs and 2,3,4-Me3-6-(r-Bu)C6HI=NTs), in the presence of CuPF6-33a complex and four olefins [80b]. This study disclosed that enantioselectivity did not depend on the iminoiodoarene, but on the olefins used, that is, the finding excludes the possibility that a Cu-Arl=NTs adduct is a key intermediate. It has also been observed that the photochemical aziridination with tosyl azide (TsN3) catalyzed... 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Following the publication of our method, similar procedures were reported by two other groups. One involves the use of bromamine-T as a nitrogen source instead of CT for the aziridination of olefins [14] the other is the copper(I) triflate-catalyzed aziridination and allylic amination with CT trihydrate [7d] (Schemes 8 and 9). 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

The aziridination of olefins has also been studied, but fewer complexes catalyze this reaction as efficiently as iron and manganese complexes catalyze the epoxida-tion of olefins. Nevertheless, the aziridinations of olefins catalyzed by copper, ruthenium, and rhodium complexes have been reported. The source of nitrogen is usually [N-(p-toluenesulfonyl)imino]phenyliodinane (PhI=NTs) or a precursor to a related iodoarylimine. The aziridine is likely generated from these copper- and rhodium-catalyzed reactions by an outer-sphere process in which the olefin interacts with the LUMO of the complex, which is located at the nitrogen. This mechanism is more likely to be followed by these catalysts than a [2-t-2] process, followed by reductive elimination. 

Kim et al. have reported that the copper complex bearing the unique dinitrogen ligand (51) catalyzes the aziridination of conjugated as well as nonconjugated olefins with good enantio-selectivity (Scheme 37).159... 

The use of metal-catalyzed aziridination methods with chiral ligands has also been reported. The copper-based system paired with ligand 56 provides the expected cinnamyl aziridine in good yield and excellent ee <06MI4568>. It is interesting to note that the /-butyl ester is obtained with 99% ee while the smaller methyl ester is obtained in only 88% ee. The binaphthyl ruthenium catalyst 57 has been found to aziridinate a number of olefins with moderate enantioselectivity <06TL1571>. Both p-nitrophenyl (Ns) and trimethylsilyloxy (SES) sulfonamides work well with this catalytic system. As is usually seen, the aziridination of aliphatic olefins proceeds in only 32% yield and 56% ee. 

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. 

A series of [A -(arenesulfonyl)imino]phenyliodanes 409 have been evaluated for their utility as nitrene precursors for the copper-catalyzed [Cu(MeCN)4C104] aziridination of various olefins 408. Best results were obtained with... 

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