Cu nitrene

Since the mid-1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. In 1969 it was reported that Cu(i) salts were capable of mediating alkene aziridination when treated with tosyl azide, but the method was limited in scope and was not adopted as a general method for the synthesis of aziridines [12]. Metaloporphyrins [13] were shown to be catalysts for the aziridination of alkenes in the presence of the nitrene precursor N-tosyliminophenyliodinane [14] in the early 1980s, but the reaction did... 

Nitrene addition to alkenes can be aided by the nse of a transition metal, such as copper, rhodium, ruthenium, iron, cobalt, etc. NHC-Cu catalysts have been used in nitrene addition. For example [Cu(DBM)(IPr)] 147 (DBM = dibenzoyl-methane) was successfully employed in the aziridination of aliphatic alkenes 144 in presence of trichloroethylsulfamate ester 145 and iodosobenzene 146 (Scheme 5.38) [43]. 

Scheme 5.40 Nitrene addition to alkenes catalysed by NHC-Cu complex...

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

A novel synthesis of isothiazolidines involves sulfonium ylides, formed by the reaction of thietanes and nitrenes <06TL1109>. Exposure of A-(/ -tolylsulfonyl)imino)phenyliodinane 232 with excess of thietanes 231 (5 equiv) in the presence of a catalytic amount of Cu(II)... 

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... 

Investigations into the mechanism of this reaction revealed several interesting facts (61). Compelling evidence was presented that a discreet Cu nitrenoid was involved in the catalytic cycle. Photolysis of a solution of tosyl azide and styrene in the presence of the catalyst afforded aziridine with the same enantioselectivity as obtained from the PhI=NTs reaction, Eq. 69. Since photolysis of tosyl azide is known to extrude dinitrogen and form the free nitrene, the authors argue that this is indicative of a common Cu-nitrenoid intermediate in this reaction. 

Electron-rich as well as electron-deficient olefinds undergo aziridination by decomposition of [A/-(/ -tolylsulfonyl)imino]phenyliodinane (19) with a catalytic amount of the soluble Cu(I) and Cu(II) triflate and perchlorate salts (Eq. 8) (91JOC6744 94JA2742). Phenyliodinane 19 acts as nitrene precursor. The Cu(I) catalyzed aziridination when applied to enol silanes... 

Carbene, nitrene, and oxo complexes of Mn-Cu represent challenging synthetic targets that would enable a better mechanistic understanding of metal-catalyzed cyclopropanation, aziridination, and oxidation reactions promoted by these complexes. By offering insights into the patterns of selectivity of these complexes, these studies may pave the way toward a rational design of a future generation of more efficient catalysts. 

Nitrene transfer to selenide is also possible. Catalytic asymmetric induction in this process has been studied with Cu(OTf)/bis(oxazoline) catalyst (Scheme 22). When prochiral selenide 206 and TsN=IPh are allowed to react in the presence of Cu(OTf)/chiral bis(oxazoline) 122b, selenimide 207 is obtained with enantioselectivity of 20-36% ee. When arylcinnamyl selenide 208 is applied to this reaction, corresponding selenimide 209 is produced which undergoes [2,3]-sigmatropic rearrangement to afford chiral allylic amides 211 in up to 30% ee. 

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). 

In 1991, Evans et al. reported that cationic Cu(I) ions catalyzed the nitrene-transfer reaction smoothly (Scheme 6B.29) [74]. Since then, many studies on asymmetric aziridination have been carried out with chiral copper(I) complexes as catalysts. 

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... 

More recently, the effect of substituents in the arenesulfonyl moiety on Cu(I)-catalyzed aziridinations of cyclohexene with a series of [(arenesulfonyl-imino)iodo]benzenes was evaluated (Scheme 65) [177]. Iminoiodanes possessing p-OMe,p-CF3, andp-N02 substituents gave higher yields of aziridines than the tosylimino analog. Product yields in these reactions are not simply related to relative rates of aziridination (p-MeO >p-Me >p-N02), and appear to reflect partitioning of the copper(III)-nitrene intermediates between aziridination of the C,C-double bond and reduction to the corresponding sulfonamides. 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

For example, Jacobsen has studied the asymmetric aziridination of alkenes using (diimine)-copper(I)-catalysts 85. The results support the intermediacy of a discrete Cu(III)-nitrene intermediate and thus suggests mechanistic similarity (particularly regarding transition state geometry) to asymmetric cyclopropanation [95JA5889]. 

Relative rates of the aziridination of styrene 397 versus a series of ra-substituted styrenes 398 furnishing the respective aziridines 401 and 402 have been determined using Tp Cu(C2H4) (Tp =hydridotris(3,5-dimethyl-l-pyr-azolyl)borate) 400 as the copper precatalyst in combination with PhI=NTs 399 as the nitrene source. The experimental data of the aziridination reaction can be fit with a two-term equation of the type log(>fx/ H) = -t-p cr" a are Jackson s radical substituent constants) leading to the values =—0.28 0.06 (polar contribution) and p = 0.34... 

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... 

Experimental observations of the aziridination of styrene-type alkenes, catalyzed by CuPF6 in the presence of chiral diimine ligands (such as (lR,2R,A i4A i4)-A A -bis(2,6-dichlorobenzylidene)cyclohexane-l,2-diamine 425), have been taken as evidence of the intermediacy of a discrete, monomeric Cu(lll)-nitrene complex, (diimine)Cu=NTs 423. Variation of the steric properties of the aryl group in the oxidant TsN=IAr (Ar = Ph, 2-/-Bu, 5,6-Me3C6H) has no effect on the enantioselectivities in forming the aziridination products 424 (Scheme 108) <1995JA5889>. 

The reaction of A -[A -(benzoylimino)-A -phenylsulfonyl]amide 429 with iodosylbenzene 426 leads efficiently to nitrene intermediates that convert olefins 411 into aziridines 430 in good yields, through a copper(ll)-mediated (Cu(OTf)2) reaction. Owing to the stereogenic sulfur atom present in the molecules, the reactions proceed with some degree of diastereoselectivity (Scheme 111) <2004OL3573>. 

The chiral sulfur(vi) reagent, A -[[J-(/i-toluenesulfonimido)-6 -(/i-tolyl)]sulfonyl]amide 431 upon reaction with iodosylbenzene 426 affords in situ the chiral iminoiodane 432. In the presence of Cu(MeCN)4PF6 as catalyst, iminoiodane 432 forms the complex 433 that very efficiently transfers the nitrene moiety together with the stereogenic information under stoichiometric conditions to a variety of alkenes 414 the corresponding aziridines 434 were obtained with diastereoselectivities up to 60% (Scheme 112) <20040L4503>. 

There are reports on the use of a Cu(l) complex of ferrocenyldiimine 465 to facilitate nitrene transfer to olefins <1998SL617>. Of particular interest for industrial applications, these reactions can also be efficiently catalyzed by... 

Styrene cyclopropanation continues to attract much interest. Cationic complex CpFe(CO)2(THF) BF4" mediates carbene transfer from ethyl diazoacetate with high cis selectivity cis trans = 85 15) [38]. On the other hand, Tp Cu(C2H4), where Tp is hydrotris(3,5-dimethyl-l-pyrazolyl)borate, is one of the rare catalysts to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes. While cyclopropanes are formed in high yield, cyclopropenes are obtained only in moderate yield [39]. The same complex also catalyzes nitrene transfer from PhI=NTs to alkenes to produce aziridines in high yields. 

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