Copper catalysis substitution

When 6-diazopenicillanates are irradiated in the presence of sulfur nucleophiles, predominantly 6/3-substitution products are obtained (77JOC2224). When BFs-EtiO is used to catalyze the reaction with nucleophiles, however, the products are primarily the 6a-isomers (78TL995). The use of rhodium or copper catalysis led primarily to ring-opened thiazepine products, presumably by way of the intermediate (56 Scheme 39) (80CC798). 

Scheme 11.6 gives some examples of the various substitution reactions of aryl diazonium ions. Entries 1 to 6 are examples of reductive dediazonization. Entry 1 is an older procedure that uses hydrogen abstraction from ethanol for reduction. Entry 2 involves reduction by hypophosphorous acid. Entry 3 illustrates use of copper catalysis in conjunction with hypophosphorous acid. Entries 4 and 5 are DMF-mediated reductions, with ferrous catalysis in the latter case. Entry 6 involves reduction by NaBH4. 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

Although the resulting vinylallenes 48 were usually obtained as mixtures of the E and Z isomers, complete stereoselection with regard to the vinylic double bond was achieved in some cases. In addition to enyne acetates, the corresponding oxiranes (e.g. 49) also participate in the 1,5-substitution (Scheme 2.18) and are transformed into synthetically interesting hydroxy-substituted vinylallenes (e.g. 50) [42], Moreover, these transformations can also be conducted under copper catalysis by simultaneous addition of the organolithium compound and the substrate to catalytic amounts of the cuprate (see Section 3.2.3). 

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

Yamamoto and coworkers studied the substitution of ally lie phosphates by Grignard reagents in the presence of copper or iron salts. Only the Sn2 product is formed under copper catalysis whereas, in the presence of iron(III) acetylacetonate, the Sn2 product is generally obtained with an excellent selectivity (Scheme 49). It should be noted that aryl-, alkenyl-, aUcynyl- and aUcyhnagnesium halides can be used successfully. 

Decomposition of l-diazo-4-arylbutan-2-ones offers a direct entry to bicyclo[5.3.0]decatrienones and the approach has been extensively used by Scott and coworkers to synthesize substituted azulenes.137 Respectable yields were obtained with copper catalysis,137 but a more recent study24 showed that rho-dium(ll) acetate was much more effective, generating bicyclo[5.3.0]decatrienones (154) under mild conditions in excess of 90% yield (Scheme 34). The cycloheptatrienes (154) were acid labile and on treatment with TFA rearranged cleanly to 2-tetralones (155), presumably via norcaradiene intermediates (156). Substituents on the aromatic ring exerted considerable effect on the course of the reaction. With m-methoxy-substituted systems the 2-tetralone was directly formed. Thus, it appeared that rearrangement of (156) to (154) was kinetically favored, but under acidic conditions or with appropriate functionality, equilibration to the 2-tetralone (155) occurred. 

The Pschorr Reaction allows the preparation of biaryl tricyclics by intramolecular substitution of one arene by an aryl radical. This radical is generated in situ from an aryl diazonium salt by copper catalysis. Although excess copper salts are used, the yield is normally moderate. 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

Cyclizations can be achieved if an organomagnesium reagent bears a remote leaving group. A stereoselective substitution without erosion of the optical purity was observed by using copper catalysis (Scheme 35).92... 

If the leaving group is excellent, namely N=N in diazonium ions, an Sis[l-like path may occur. The many mechanisms for substitution on these diazonium ions are complex some involve electron transfer, radical intermediates, or copper catalysis (Chapter 11). 

By analogy, the 3-methoxycarbonyl-l-propylcyclopropene ring opens under copper catalysis and can react with strained alkenes.Bisdonor-substituted cyclopropenes, such as 3,3-... 

Allyl methyl ether (ethyl diazoacetate, rhodium catalysis) and allyl terf-butyl ether (dimethyl diazomalonate, copper catalysis) yield cyclopropanes exclusively. With y-substituted allyl methyl ethers, C-0 insertion is generally strongly favored over cyclopropanation, even with tetraacetatodirhodium as catalyst.In view of these findings, the cyclopropanation of ( )- ,4-dibenzyloxybut-2-ene in moderate yield, only, to give (la,2a,3j5)-31 is notable. 

Transient phosphoryl-substituted carbenes, generated by photolysis or by copper catalysis, react selectively with one double bond of a 1,3-diene affording mixtures of trans- and c -isomers which, in some cases, can be separated by column chromatography on silica gel or by distillation (Table3). ... 

The p/fa for benzimidazole is 12.3 and for indazole, the value is 13.9. The benzimidazolyl and indazolyl anions react straightforwardly on nitrogen with electrophiles, though mixtures of N-1- and N-2-substituted products can result in the latter case. For example, amination with hydroxylamine 0-suIfonic acid gives a 2 1 ratio of 1-amino-l//-indazole and 2-amino-2//-indazole ° or to take another example, the ratio of N-1-to N-2-ethylated products from methyl indazol-3-ylcarboxylate can vary from 1 1 to 18 1 depending on the base and the solvent. The N-arylation of benzimidazoles and indazoles can be achieved with palladium or copper catalysis (See 4.2.10). 

It is now usual to promote these cycloadditions by catalysts for example, reaction with A -tosyl-ynamides, using ruthenium or copper catalysts, giving 1-substituted 5- and 4-amino triazoles, respectively the formation of the 1,4-substitution pattern with copper catalysis and 1,5-pattem with ruthenium catalysis seems to be general. The latter metal will also promote addition to internal alkynes. ... 

Copper(II)-substituted zinc proteins are generally inactive with respect to the natural and most artificial substrates (Table 2.4). In model compounds cop-per(II) is often principally four-coordinate, with at most two more ligands present at metal-ligand distances that are longer than normal coordination bonds. As a consequence, tbe ability of zinc to switch between four- and five-coordinate species without any appreciable barrier and with usual metal-donor distances is not mimicked by copper. Furthermore, binding at the four principal coordination positions is generally stronger for copper than for zinc. It follows that substrates may have slow detachment kinetics. These properties are unfavorable for catalysis. 

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