Thioether copper

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Chloroquinoline (401) reacts well with potassium fluoride in dimethylsulfone while its monocyclic analog 2-chloropyridine does not. Greater reactivity of derivatives of the bicyclic azine is evident also from the kinetic data (Table X, p. 336). 2-Chloroquinoline is alkoxylated by brief heating with methanolic methoxide or ethano-lic potassium hydroxide and is converted in very high yield into the thioether by trituration with thiocresol (20°, few hrs). It also reacts with active methylene carbanions (45-100% yield). The less reactive 3-halogen can be replaced under vigorous conditions (160°, aqueous ammonia-copper sulfate), as used for 3-bromoquino-line or its iV-oxide. 4-Chloroquinoline (406) is substituted by alcoholic hydrazine hydrate (80°, < 8 hr, 20% yield) and by methanolic methoxide (140°, < 3 hr, > 90% yield). This apparent reversal of the relative reactivity does not appear to be reliable in the face of the kinetic data (Tables X and XI, pp. 336 and 338) and the other qualitative comparisons presented here. 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

A remarkable case of a Meerwein reaction of phenylacetylene was reported by Leardini et al. (1985) in a new synthetic route to benzothiophene derivatives. Aryldi-azonium salts with a thioether group in the 2-position add phenylacetylene and substituted phenylacetylenes in the presence of metallic copper or iodide ion in acetone, or of FeS04 in DMSO (Scheme 10-60). The radical 10.21 formed initially is attacked intramolecularly by the sulfur atom of the thioether group to give the benzothiophene 10.22 in high yields (55-95%) as shown in (Scheme 10-60). Lear-... 

Azoresorcinol, pyridyl-metal complexes dyes, 6, 74 Azurins, 6, 651, 652 copper(II) complexes, 2, 772 5, 721 electron transfer reactions, 6, 653 NMR, 6, 652 Raman spectra, 6, 652 spectra, 6, 652 thioether complexes, 2, 557 Azurite... 

From the standpoint of modeling Type I copper proteins,4,5,59,60 a variety of imidazole-based ligands containing thioether sulfurs and imidazole groups have been synthesized.61,62 The structures and spectroscopic properties of their copper(II) complexes (51)-(53) and (55)-(60) were investigated.65,79-82 To characterize apical copper(II)-thioether bonding, the complex (51) was... 

A few thioether-ligated copper(II) complexes have been reported, however (cf. Section 6.6.3.1.2) (417) (essentially square planar), (418) (two crystalline forms one TBP and other SP),361 (419) (SP),362 (420) (SP),362 (421) (TBP),362 (422) (SP),363 (423) (SP),363 (424) (two independent complexes SP and octahedral),364 (425) (TBP).364 In the complexes (420) and (421), EPR spectra revealed that the interaction between the unpaired electron and the nuclear spin of the halogen atom is dependent on the character of the ligand present. For (424) and (425), spectral and redox properties were also investigated. Rorabacher et al.365 nicely demonstrated the influence of coordination geometry upon CV/Cu1 redox potentials, and reported structures of complexes (426) and (427). Both the Cu1 (Section 6.6.4.5.1) and Cu11 complexes have virtual C3v symmetry. 

To gain insight into electron-transfer kinetics of copper(II/I) complexes of macrocyclic thioethers,446,447 Rorabacher and co-workers reported448,4 7 structures of five complexes (complexes (548)-(552)). 

It has been recognized that sulfur donors aid the stabilization of Cu(i) in aqueous solution (Patterson Holm, 1975). In a substantial study, the Cu(ii)/Cu(i) potentials and self-exchange electron transfer rate constants have been investigated for a number of copper complexes of cyclic poly-thioether ligands (Rorabacher et al., 1983). In all cases, these macrocycles produced the expected stabilization of the Cu(i) ion in aqueous solution. For a range of macrocyclic S4-donor complexes of type... 

Model systems for Type I copper proteins structures of copper coordination compounds with thioether and azole-containing ligands.17... 

Copper, Cu+(d10), Cu2+ (d9) 4, tetrahedral N-Thiolate, thioether, AMmidazole Electron transfer in Type I blue copper proteins... 

The inactive form GOin, which displays a typical Cu(II) EPR signal, yields upon one-electron oxidation the EPR silent active form GO0X. For many years the presence of a Cu(III) ion (ct,. S = 0) in the active site (121) of the fully oxidized state GO0X was assumed. The Whittakers (122) showed in 1990 that one-electron oxidation of the copper depleted apoenzyme of GO produced an EPR active, remarkably stable Tyr radical that was studied by UV-vis, EPR, and ENDOR spectroscopy. From these studies, they concluded that the thioether modified Tyr 272 was oxidized and, consequently, they proposed that GOcx contains a Tyr 272 radical coordinated to a Cu(II) ion. 

Synthesis. The first example of a stable, soluble pz peripherally substituted with a heteroatomic moiety involved appended thioether groups, M[pz(.V-Mc)8, as reported in 1980 by Schramm and Hoffman (2) (Scheme 9, 45-48). Mg[pz(5 -Me)s], 46, was prepared in a 60% yield by a magnesium templated macrocyclization of dinitrile, 45. Demetalation with sulfuric acid gave H2[pz(5 -Me)8], 47 (65%) and remetalation with the anhydrous acetate salts of copper and nickel gave 48 (80%) and 49 (65%). 

The localization of a double bond is an important step in structure elucidation and therefore, it is not astonishing that numerous approaches have been made to overcome the above limitations. The methods to freeze isomerization include i) epoxidation [64], ii) iron and copper ion chemical ionization [65,66], iii) field ionization [67], iv) collision-induced dissociation [60], v) formation of thioether derivatives, [68,69] and others. 

Wipf has shown that this method is quite general and tolerates several functional groups, such as ethers, thioethers, silanes, halides, aromatic rings, and olefins. The iodoalkyne 64 is readily carbometalated and after treatment with the dialkynylcuprate 59 furnishes the functionalized copper reagent 65, which smoothly undergoes 1,4-addition reactions with enones. Thus, in the case of 2-cyclohexenone, the functionalized ketone 66 is produced in 85% yield (Scheme... 

Transmetalation of thioethers to organocopper compounds can also be performed in some special cases. Thus, treatment of the ester 119 with Me2CuLiLiCN provides the copper reagent 120, which can be treated successfully with several electrophiles such as allyl bromide or acid chlorides to afford the expected products such as 121 (Scheme 2.54) [115, 116]. 

Copper, Cu (d °), Cu " (d ) 4, tetrahedral Y-Thiolate, thioether, A-imidazoIe Electron transfer in Type I bine copper proteins and Type III heme-copper oxidases (Cua in cytochrome c oxidase, for example)... 

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