Intramolecular copper-catalyzed aziridination

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>. 

Intramolecular copper-catalyzed aziridinations of sulfamates have been reported in yields up to 86% and up to 84% ee using (4>V,4 S)-2,2 -(propane-2,2-diyl)bis(4-/erf-buty 1-4,5-dihydro-l,3-oxazole), 43 <07S1251 >. 

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-... 

An SN2-type ring-opening of N-activated aziridines 105 with a 2-bromobenzyl alcohol/thiol 106, followed by a copper-catalyzed intramolecular N-arylation reaction, afforded the corresponding tetrahydrobenzox(thi)azepines 107 in good yields (14JOC6468). 

A copper-catalyzed enantioselective aziridination of aryl cinnamyl ethers and intramolecular arylation of the in situ generated tethered aziridine was developed by Hajra and Sinha. This method provides an easy access of N-sulfonyl-protected fra s-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99 1), and enantioselectivity (ee up to 95%) (Scheme 8.113). Three C(sp )-H bonds were activated in this transformation under this Cu(0Tf)2/Cu(C10 )2-6H20 catalyst system. The major side reaction is the C-H insertion of nitrene at the O-CH2 unit followed by oxidative cleavage [188]. 

Synthesis of benzoxazines through aziridine ring opening followed by intramolecular C—N bond formation was reported by Sekar and co-workers. " In this approach, a domino ring opening of A -Ts aziridines 332 with o-iodo-phenols 333 followed by copper-catalyzed intramolecular C(aryl)-N(amide) bond formation in the presence of ethyl-enediamine ligand has been established to afford the resultant product 334 in excellent yield (Scheme 40.73). The trans selectivity was confirmed by H NMR spectroscopy and single crystal X-ray analysis. 

The trans-3,4-dihydro-2//-l,4-benzoxazines could be obtained conveniently by ring opening of aziridines 193 with o-iodophenols 194 and subsequent copper-catalyzed intramolecular N-arylation (Scheme 68) [113]. 

Thus far, enantioselective intramolecular aziridination via metal nitrene intermediates has not been successful. Bromamine-T has recently been shown to be a viable source of nitrene for addition to alkenes in copper halide catalyzed reactions, " and so has iodosylbenzene (Phl=0) that forms 44 in situ. Conceptually, aziridination does not necessarily fall between cyclopropanation and epoxidation, as some have suggested. Instead, metal nitrene chemistry has unique problems and potential advantages associated with the electron pair at nitrogen that are yet to be fully overcome. 

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... 

After successful application of the silver catalyst shown in olefin aziridination (Section 6.1.1), He and coworkers showed that intramolecular amidation was possible with both hydrocarbon-tethered carbamates and sulfamate esters.24 They found that only the Bu3tpy silver complex could catalyze efficient intramolecular amidation, while other pyridine ligands gave either dramatically lower yields or complicated product mixtures. In an interesting control study, both copper and gold were also tested in this reaction. Both the copper and gold Bu tpy complexes can mediate olefin aziridination, but only silver can catalyze intramolecular C-H amidation, indicating that the silver catalyst forms a more reactive metal nitrene intermediate. 

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