From Noble Metal to Nobel Prize: Palladium-Catalyzed Coupling Reactions Giovanni Piersanti 26/10/2011 and 02/11/2011

Palladium? Beautiful, but expensive jewellery metal (Noble Metals) Car as part of the automotive catalysts(with Pt and Rh), where palladium is used to eliminate harmful emissions produced by internal combustion engines. Electrodes (Pd/H2 as a reference) Electronics for multi-layer ceramic capacitors (MLCC). These MLCC are used in electrical components for cellular telephones, personal and notebook computers, fax machines and in auto and home electronics. Dental alloys.

Periodic Table 046_Palladium.htm On the other hand, and not known to the general public, is the essential role of palladium catalysts in contemporary organic chemistry, a topic which has now been recognized with the Nobel Prize for Chemistry Nobel_prizes_chemistry_2010

Palladium-based catalysts Palladium-catalyzed cross-coupling reactions Creation of new C-C bonds R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37, T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581. K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975, 16, E. Negishi, A. O. King, N. Okukado, J. Org. Chem. 1977, 42, Miyaura, Norio; Yamada, Kinji ; Suzuki, Akira Tetrahedron Letters 1979, 20, 3437 Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636 Y. Hatanaka, T. Hiyama, J. Org. Chem. 1988, 53, 918;

a) D. S. Surry, S. L. Buchwald, Angew. Chem. Int. Ed. 2008, 47,6338; b) J. F. Hartwig, Acc. Chem. Res. 1998, 31, 852. The Tsuji-Trost Reaction Trost, B. M.; Fullerton, T. J. "New synthetic reactions. Allylic alkylation.” J. Am. Chem. Soc. 1973, 95, Trost, B. M.; Dietsch, T. J. "New synthetic reactions. Asymmetric induction in allylic alkylations." J. Am. Chem. Soc. 1973, 95, This process is particularly useful for the coupling of two alkyl units, and the asymmetric veriant is commonly used in total synthesis. Gaining popularity….. Buchwald-Hartwig Coupling

Cyanation of aryl halides

Where everything started from ????? Angew. Chem. 1959, 71, 176.Wacker-Tsuji Oxidation Angew. Chem. Int. Ed. 2009, 48, 9034 – 9037: and butanale and acetic acid replace; acetone e butanone still active--- BOOM- C-C bond-forming process (Heck reaction), vynilacetate, allyl complex of palladium (pigreco-allyl comlplex).

Since then…….palladium-catalyzed cross-coupling reactions have come a long way, continuing popularity and success. Tolerance of a wide range of functional groups on both coupling partners. Hence, it is possible to construct complex organic building blocks efficiently in fewer steps than by traditional stoichiometric reactions. The development of ligands and co-catalysts allows for a fine-tuning of the reactivity. Hence, it is not surprising that these reactions are widely employed for various applications. Easy transfer from gram-scale synthesis in academic laboratories to ton-scale production in the pharmaceutical, agrochemical, and fine-chemical industries. Hence, Nobel Prize being awarded for the three major coupling reactions: The Heck reaction, the Negishi coupling, and the Suzuki coupling reaction a)K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005, 44, 4442; b)C. Torborg, M. Beller, Adv. Synth. Catal. 2009, 351, 3027.

Heck Reaction In the Heck reaction (probably better called as the Mizoroki–Heck reaction) (hetero)aryl, alkenyl, and benzyl halides are coupled with all kinds of alkenes in the presence of palladium catalysts to give the corresponding substituted alkenesIn general. ln the reaction proceeds with high stereo- and regioselectivity. Syn addition, internal rotation, Syn elimination

Heck Reaction In the Heck reaction (probably better called as the Mizoroki–Heck reaction) (hetero)aryl, alkenyl, and benzyl halides are coupled with all kinds of alkenes in the presence of palladium catalysts to give the corresponding substituted alkenesIn general. ln the reaction proceeds with high stereo- and regioselectivity.

Negishi Coupling Ei-ichi Negishi and his group studied fundamental aspects of the coupling of various organometallic derivatives including aluminum, magnesium, zinc, and zirconium compounds with aryl halides in the presence of palladium or nickel catalysts. However, the name Negishi coupling is nowadays associated with the nickel- and palladium-catalyzed crosscoupling reaction of organozinc compounds and organohalides. In addition to classical C(sp2) C(sp2) bond formation, the coupling of alkylzinc compounds allows for the formation of C(sp3)C(sp2) and C(sp3)C(sp3)

Suzuki Coupling Organoboronic acids and boronates are able to transfer their organic moieties to the palladium center in base- assisted transmetalation reactions. Nowadays, the Suzuki reaction is probably the most important method for the synthesis of all kinds of biaryl derivatives.

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