Copper catalysis alkylation

Sulfur dioxide (see above) as well as S02, SO , and SOj have been used as building blocks in three-component sulfone syntheses. It has long been known that aromatic sulfinic acids are easily available from diazonium salts and sulfur dioxide under copper catalysis . Mechanistically, aryl radicals as reactive intermediates add to sulfur dioxide generating arenesulfonyl radicals, which either take up an electron (or hydrogen) yielding a sulfinic acid or add to an olefinic double bond yielding final y -halogenated alkyl aryl sulfones (equation 78). 

Zinc homoenolate reacts with allylic halides and diene monoepoxides under copper catalysis [29]. Treatment of the zinc nomoenolate with a catalytic amount of Cu(II) in a polar solvent (e.g. hexamethylphosphoramide, HMPA, N,N-dimethylacetamide, DMA) generates a copper species which undergoes clean Sn2 allylation reactions Eq. (40). Polar solvents not only accelerate the reaction but greatly improve the SN2 selectivity. A variety of allylating reagents can be employed in this reaction (Table 9). The SN2 /SN2 ratio is particularly high (close to 100%) when the alkylated carbon bears no substituents. The reaction of... 

Metal catalysed cyclopropanation using other types of intermediate is also possible. Lithiated tert-butyl alkyl sulphones bring about the cyclopropanation of various nonactivated alkenes under nickel(II) acetylacetonate catalysis (equation 88)131,132. Sulphonium ylides of type 90 react with simple alkenes under copper catalysis to give the corresponding cyclopropane adduct (equation 89)113,134. In this example the ylide (90) is the sulphonium equivalent of ethyl diazoacetate134. 

The products formed in these reactions are very sensitive to the functionality on the carbenoid. A study of Schechter and coworkers132 using 2-diazo-1,3-indandione (152) nicely illustrates this point. The resulting carbenoid would be expected to be more electrophilic than the one generated from alkyl diazoacetate and consequently ihodium(II) acetate could be used as catalyst. The alkylation products (153) were formed in high yields without any evidence of cycloheptatrienes (Scheme 33). As can be seen in the case for anisole, the reaction was much more selective than the rhodium(II)-catalyzed decomposition of ethyl diazoacetate (Scheme 31), resulting in the exclusive formation of the para product. Application of this alkylation process to the synthesis of a novel p-quinodimethane has been reported.133 Similar alkylation products were formed when dimethyl diazomalonate was decomposed in the presence of aromatic systems, but as these earlier studies134 were carried out either photochemically or by copper catalysis, side reactions also occurred, as can be seen in the reaction with toluene (equation 36). 

The iodine-zinc exchange of an alkyl iodide with EtjZn is proi oted by the addition of small amounts of copper(I) salts such as CuCN or Cul. Although the exact reason for this copper catalysis is now known, it has been speculated that the presence of copper(I) salts promotes a radical chain-reaction resulting in the formation of a dialkylzinc species (Scheme 9-32) [22b]. Similarly, the addition of other transition metals such as nickel and palladium salts promotes radical reactions. 

Although 1,2-addition of Grignard reagent to N-alkyl-N-silylformamide aflforded the same type of product, imines, in the presence or absence of a copper salt, N-phenyl-N-silylformamide afforded a doubly alkylated amine in the reaction of Grignard reagent under copper catalysis [Eq. (73) 152]. 

Isonitriles add carboxylic acid chlorides to yield oi-oxoimidoyl chlorides (210 equation 117). 1.3.5395,396 With copper catalysis, from perfluorinated alkyl iodides and isonitriles imidoyl iodides (211 equation 118) can be obtained. - Alkenes react with nitriles in the presence of HF or to afford the... 

By derivatizing an a,p-unsaturated acid into the mono ester of chiral 1,1 -bi-8,8 -naphthol the reaction with lithium dialkylcuprates leads to saturated ketones containing chirality centers at the p-carbon atoms." Consecutive 1,4-addition and 1,2-addition account for this result. The alkyl transfer to enones from Grignard reagents under copper catalysis is subject to chiral modification, e.g., by the introduction of 56" or 57." ... 

Titanium alkoxides (ethoxide, isopropoxide and tert-butoxide) were also used recently for catalyzing the production of substituted indoles,with acceptable yields from cyclization of o-bromobenzylketones, 89, and primary alkyl amines or anilines, 90 (reaction 7.15) [65]. Melkonyan et al. proposed that the reaction sequence includes a titanium alkoxides catalysis reaction of ketones with amines to give imines and following intra-molec-ular cyclization into indoles, 91, using copper catalysis. Without titanium catalyst and amines the product of cyclization was almost 92. 

Scheme 3.3 Domino conjugate reduction-allylic alkylation reaction catalysed by a combination of copper catalysis and chiral palladium catalysis.

In the same year, Chi et al. developed an enantioselective oxidative coupling of tertiary amines with ahphatic aldehydes by combination of copper catalysis and aminocatalysis (Scheme 2.6) [31]. Both A -Aryl tetrohydroisoquinolines and simple A-Aryl tertiary amines can undergo this enantioselective alkylation reaction. Soon afterwards, organocatalytic enantioselective CDC reaction of ethers with aliphatic aldehydes [32] and Cu-catalyzed asymmetric CDC reaction of iV-carbamoyl tetrahydroisoquinohnes with terminal alkynes [33] were reported. 

The alkylation of simple Grignard and organolithium compounds requires copper catalysis (Eq. 7.6) [15]. 

The main products of the thermolysis of the isomeric oxadiazolinones (642) and (644) are the benzimidazole (643) and the rearranged compound (645), respectively. The rates of the oxadiazole - triazole rearrangement (646) - (647) have been measured. Oxadiazoline-thiones (648 R R = alkyl or Ph) rearrange photochemically or by copper catalysis to thiadiazolinones (649). ... 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

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