Suzuki reaction intramolecular palladium coupling

A more sophisticated procedure has recently allowed the preparation of palladium complex 34, based on an intramolecular Suzuki coupling. The key intermediate 39 is generated by oxidative addition of palladium(O) to 38, and treatment of 39 with base promotes a Suzuki-type intramolecular reaction leading to 34 (Scheme 7) [26]. The same procedure is applicable to the synthesis of benzyne-nickel complexes with a variety of ligands (PPh3, PCy3, PEt3) [26]. 

Miyaura, N. Ishiyama, T. Sasaki, H. Ishikawa, M. Sato, M. Suzuki, A. (1989) Palladium catalyzed inter- and intramolecular cross-coupling reaction of. 5-alkyl-9-borabicyclo[3.3.1]-nonane derivatives with 1-halo-1-alkanes or haloarenes, / Am. Chem. Soc., Ill, 314-21. 

Another Suzuki coupling reaction was described by Zhang et al., to produce arylindoles 116a and b, using solid-phase synthesis [76]. The synthesis was achieved by palladium-mediated coupling/intramolecular indole cycli-zation of resin-bound 2-trimethylsilylindole 117, Scheme 29. 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

B.i.c. Pd(OAc)2 + nL(n 3) as Precursor of Three-Coordinate Anionic Pd L OAc) (L = PPhj). Pd(OAc)2 + nL] mixtures were initially introduced as catalysts in Heck reactions but are also involved in Suzuki cross-coupling of organoboranes. " In both cases, a palladium(O) is mechanistically required to activate aryl halides C—X bonds. However, the origin of the paUadium(O) center has remained unknown, since no clearly identified reducer is present in the catalytic reactions. A quantitative kinetic study of this system has established that addition of 3 equiv of PPhs to Pd(OAc)2 quantitatively generates a stable palladium(O) complex through an intramolecular reduction of the palladium(II) to paUadium(O), a process by which the phosphine is oxidized to phosphine oxide, (OjPPhj (Scheme 5). 

The coupling reaction may be either intermolecular, as for a synthesis of an intermediate in a synthesis of thyroxine 2.605 (Scheme 2.179), or intramolecular, as in a synthesis of a metalloproteinase inhibitor 2.607 (Scheme 2.180) (for a different approach to related peptides, see Scheme 10.47). It is notable in the thyroxine synthesis that the two iodine substituents of coupling substrate 2.602 are not affected and no Suzuki products are formed in the absence of palladium. 

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