Palladium couplings

The Suzuki-Miyaura reaction, first reported by Suzuki and co-workers in 1979 [87], is the metal-mediated (often palladium) coupling of organic electrophiles such as alkenyl... 

After preliminary evaluation of the discovery route (scheme 1), we concluded that the overall yield of RWJ-26240 should be improved and that the use of NaCNBH. should be eliminated, since it produces a waste stream containing HCN or NaCN. Replacement of the expensive silver reagent, silver acetate, would permit significant cost reduction. The copper-catalyzed palladium coupling step would lead to palladium as a contaminant in the final product.177 Since a drug substance containing palladium would not be acceptable, this step would also have to be revised. 

Next, reductive amination (step 4 in scheme 1) was exchanged with copper catalyzed palladium coupling (step 2 in scheme 1). Atomic absorption analysis for palladium in RWJ-26240 samples prepared by scheme 2 indicated that the level of palladium was reduced to an acceptable level. This improvement may be due to the two reduction steps subsequent to the use of palladium in scheme 2.177 The final major modification to the reaction scheme was the substitution of NaBH4 for NaBH3CN. The yield of product (60%) was determined by HPLC (Method 2). Reductive alkylation with formalin/NaBH4 afforded a pharmaceutically acceptable drug substance. 

Wagner, R. W. Ciringh, Y. Clausen, C. Lindsey, J. S. Investigation and refinement of palladium-coupling conditions for the synthesis of diarylethyne-linked multiporphyrin arrays. Chem. Mater. 1999,11, 2974-2983. 

The palladium-catalyzed formation of sulfides can generate polyphenylene sulfide from a dithiol and a dibromoarene, or from 4-bromobenzenethiol (Equation (38)).17 In 1984 Asahi Glass obtained patents for the formation of this polymer in the presence of palladium and nickel catalysts.125,126 In addition, Gingras reported palladium-catalyzed couplings of aryl halides and thiols to form discrete phenylene sulfide oligomers.127,128 A number of polyphenylene sulfide wires, ranging from dimeric to pentameric structures, were prepared by the palladium coupling, albeit in modest yields ... 

Intramolecular oxidative palladium couplings of alkenylamino indoles allow the preparation of azepinoindole derivatives in high yields (2005MI707). 

Substitution of halogen atom in non-activated rings such as 33 (equation 23) is substantially more difficult. Palladium couplings are the most promising approach, although... 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

Scheme 26 Synthesis of Optically Pure Ferrocenylalanines 91 and 93 via a Palladium Coupling 63 -I...

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

Arasabenzene, with chromium, 5, 339 Arcyriacyanin A, via Heck couplings, 11, 320 Arduengo-type carbenes with titanium(IV), 4, 366 with vanadium, 5, 10 (Arene(chromium carbonyls analytical applications, 5, 261 benzyl cation stabilization, 5, 245 biomedical applications, 5, 260 chiral, as asymmetric catalysis ligands, 5, 241 chromatographic separation, 5, 239 cine and tele nucleophilic substitutions, 5, 236 kinetic and mechanistic studies, 5, 257 liquid crystalline behaviour, 5, 262 lithiations and electrophile reactions, 5, 236 as main polymer chain unit, 5, 251 mass spectroscopic studies, 5, 256 miscellaneous compounds, 5, 258 NMR studies, 5, 255 palladium coupling, 5, 239 polymer-bound complexes, 5, 250 spectroscopic studies, 5, 256 X-ray data analysis, 5, 257... 

Allenylsilver compounds appear to enter the palladium coupling catalytic cycle via transmetallation. It was found that tert-butyl allenylsilver, and the corresponding argentate derivative, underwent palladium-catalyzed coupling with iodobenzene to... 

Loar, M. K., Stille, J. K. Mechanisms of 1,1-reductive elimination from palladium coupling of styrylmethylpalladium complexes. J. Am. 

Molander has published a series of papers demonstrating the utility of potassium alkyl, alkenyl-, alkynyl-, and aryltrifluoroborates in palladium coupling reactions. The crystallinity and air-stability of these trifluoroborate salts make the use of these an interesting alternative to the use of boronic acids or esters. Good yields have been obtained in several related palladium coupling processes, which are most easily classified as Suzuki couplings. The broad applicability of this process is demonstrated by the production of 58 [40], 59 [41], and 60 [42]. 

Ubichem is an independent British company which was founded in 1978 with the aim of supplying a wide range of fine chemicals and intermediates. Its literature review section at http //www. ubichem.com/lit.php has reports on a variety of chemical topics, including isoquinolines, palladium coupling, azides, and radiolabeling. 

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