Stille coupling copper effect

Stille Coupling. Copper(I) chloride can affect intra- and inter-molecular StiUe couplings in the absence of a palladium source, although 2 equiv of CuCl are required. Moreover, copper(I) chloride has been identified as a general and effective additive in the Stille coupling of sterically congested substrates in DMSO at60°C (eq 21). ... 

The Stille coupling of 2-chloro-5-tributylstannylpyridine with an enantiopure 2-iodo-cyclohexenon (7.29.) derivative formed the basis of the total synthesis of (+)-epibatidine. The reaction is a nice example of the chemical inertness of arylstannanes and the mildness of the coupling conditions. Both the enone moiety and the chiral ally lie centre remained untouched in the process. The effective coupling required the use of a soft ligand, triphenylarsine and the addition of copper(I) iodide as co-catalyst.40... 

The synthesis of pyrone derivatives attracted attention due to their synthetic potential. In an illustrative example Cho and co-workers studied the Suzuki-coupling of 3,5-dibromo-2-pyrone with arylboronic acids (8.9.). Under regular conditions the aryl group is introduced selectively into the more electron deficient 3-position, while in the presence of an equimolar amount of copper(I) iodide the coupling is diverted selectively into the 5-position (N.B. drop of the reaction temperature from 50 °C to ambient temperature negated the effect of copper and led to 3-arylation). The way copper effects the coupling is still unclear, but it was successfully used in the preparation of a range of 5-aryl-2-pyrons.17... 

The rate-enhancing influence of Cu(l) salts (the so-called "Copper Effect") in normally nonproductive and sluggish Stille couplings was first pointed out by Liebeskind et al.6 in 1990. A greater insight into this phenomenon was obtained later by Farina and co-workers.7 A number of modifications of the Stille reaction have since... 

Finally, a new effect of the addition of copper salts was noted recently. The regioselectivity of the Stille coupling of 3,5-dibromo-2-pyrone can be modified in the presence of Cul in DMF as the solvent, leading to the products shown in Scheme 5.3.5. ... 

Bromo- and 4-bromoalkyl-2,5-diphenyloxazole 38 were subjected to the Stille coupling with a range of commercially available tributyltin reagents. Tri-2-furylphosphine/ Pd2(dba)3 was used as an effective catalyst. Copper(n) oxide enhanced the Stille coupling reactions of 2,5-diphenyl-4-tributylstannanyloxazole with various electrophiles [41]. Such method offered an efficient synthetic route to prepare resins from oxazole-containing monomers such as 2,5-diphenyl-4-vinyloxazole. 

It is reported in literature that additives like LiCl or Cu(I) salts can have a dramatic influence on the coupling. The copper effect in Stille coupling reactions was investigated by Farina and Liebeskind and coworkers. For instance in the reaction of iodobenzene and vinyltributyltin in dioxane at 50 °C catalyzed by Pd2(dba)3 in presence of a strong ligand like PPhs, it was found that the addition of 2 molar equivalents of Cul per mol of catalyst led to a > 100 fold increase in reaction rate. 

Taking advantage of the copper and fluoride effects, Baldwin and co-workers have developed conditions (Pd(PPh3)4/CuI/CsF) that allow the Stille coupling of electronically unfavourable and/or sterically hindered... 

Farina V, Kapadia S, Krishnan B, Wang C, Liebeskind LS. On the nature of the copper effect in the Stille cross-coupling. J. Org. Chem. 1994 59(20) 5905-5911. 

Since its introduction by Allred and Liebsekind in 1996 [114], copper thiophene-2-carboxylate (CuTC) has emerged as a mild and useful reagent for mediating the cross-coupling of organostannanes with vinyl iodides at room temperature. CuTC is especially effective for substrates that are not stable at high temperature. In Paterson s total synthesis of elaiolide, he enlisted a CuTC-promoted Stille cyclodimerization of vinyl iodide 131 to afford the 16-membered macrocycle 132 under very mild conditions [115]. 

The hydrogenation is carried out in a low-pressure vapor phase process, i.e., at around 473 K and under a few megapascals of H2 pressure. Known effective catalysts include copper-chromium catalysts, and palladium-carbon catalysts, etc. The process can be coupled with maleic anhydride production units, using either benzene or butane feedstocks, and units to separate and refine GBL, THF, and BDO products. Fig. 3 shows a chart of such a process design. Other catalysts with higher activities allowing the process to be conducted at still lower temperatures in the liquid phase are under development. 

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