Palladium-Catalyzed Cross-Coupling - A Historical Contextual Perspective to the 2010 Nobel Prize

Palladium-Catalyzed Cross-CouplingAngewandteChemiereactions, with the aim of increasing functional-group compatibilityand broadening the substrate scope. The importanceof these modifications and manipulations cannot be underestimated,since they made it possible to begin employingcross-coupling chemistry in the synthesis of biologicallyimportant molecules, particularly on large scale. We will notbe concerned with details of the modifications of thesereactions, which we call fine-tuning, rather, a brief account ofthe historical order of events is given. [114]3.1. The Importance of Ligand PropertiesDuring the early years in the development of crosscouplingreactions, the readily available PPh 3 was the ligandof choice. As the possibilities of improving reaction conditionsand increasing substrate scope by changing theorganometallic reagent progressed, the nature of the ligandemployed became recognized as the most important variablefor detailed investigation. Gradually, researchers started tomap the effects of the choice of ligand upon the steps in thecatalytic cycle (oxidative addition, transmetalation, andreductive elimination).Kumada noted, as early as 1979, the beneficial effects ofthe bidentate ligand dppf in the palladium-catalyzed couplingreaction of Grignard reagents with organic halides(Scheme 23). [115] It is now well appreciated that the use ofbidentate ligands accelerates the reductive-elimination step inthe catalytic cycle, thereby increasing the overall rate of thereaction. Achieving a faster and more favorable reductiveeliminationstep also means less competition from the b-hydride-elimination side-product formation. [116]Scheme 23. Ligand effects in the Corriu–Kumada reaction with alkylGrignard reagents. [115]In the following years, the profound effect of choice ofligand, in not only the Corriu–Kumada reaction, but also theother named cross-coupling processes was repeatedly noted.Since then, many sophisticated and effective bidentate ligands(P P, P N, P C, P O) have been developed. The geometricparameter “cone angle” was formulated by Tolman, [117] andthe concept of “bite angle” [118] was introduced in relation tobidentate ligands. Initially, only the steric properties of themainly aryl-derived ligands were investigated. In the early1980s, Heck recognized that the palladium complex derivedfrom the tri-o-tolylphosphine ligand, which is sterically moreencumbered than triphenylphosphine, had increased activitycompared to [Pd(PPh 3 ) 4 ]. [119] A year later, Spencer reportedthat the combination of Pd(OAc) 2 and P(o-tol) 3 achievedparticularly high turnover numbers in cross-coupling reactions,and suggested that this could not simply be attributed tothe bulk of the ligand. [120] The structure of the catalyticallyactive species was later shown by Herrmann and Beller to bea palladacycle formed upon heating Pd(OAc) 2 and P(o-tol) 3in a suitable solvent. [121] In the same year as the Kumadapublication on alternative ligands, Osborn reported the use ofPCy 3 as a ligand in carbonylation reactions, and noted that“significant catalytic activity is found only with phosphineswhich are both strongly basic (pK a > 6.5) and with well-definedsteric volume, that is, the cone angle must exceed 1608” [122]clearly informing chemists that the electronic properties of thephosphine were often also crucial for the catalytic activity.During the same period, Milstein employed the electron-richbidentate ligand, 1,3-bis(diisopropylphosphino)propane(dippp) for the reductive carbonylation of chlorobenzene. [123]These considerations started new waves in the cross-couplingchemistry field, stimulating the preparation of more reactivecatalyst complexes. Thus, coupling partners that had notpreviously been suitable for cross-coupling reactions, owingto either their lack of reactivity or their propensity to undergounwanted side reactions, could now be included in thesubstrate scope. Even before Osborns observations, Nicholasdemonstrated the use of the pyrophoric PtBu 3 in palladiumcatalyzedcarbonylative amidation of vinyl chlorides. [124] Fuand Koie subsequently and independently expanded thescope of Pd/PtBu 3 -based catalysts in coupling reactionsinvolving unactivated substrates, such as, aryl chlorides. [125]Fus original publications in 1998 rekindled the interest [125a] ofboth academic and industrial scientists to seriously revisit thearea and hence played an important role in the rapid growthof ligand variation studies in the last decade. In 2000, Fu andco-workers reported the use of pyrophoric, bulky electronrichPtBu 3 and the relatively less air-sensitive PCy 3 in Suzuki–Miyaura couplings, for coupling of aryl boronic acids withC(sp 2 )-halides and C(sp 2 )-triflates, respectively. [126] This workdramatically illustrated that impressive chemoselectivities areattained through appropriate ligand selection as a reversal inthe reactivity order of Ar OTf and Ar Cl observed betweenthe two ligand sets. DFT calculations by Schoenebeck andHouk provided an explanation for the origins of the chemosectivity.[127] These studies indicated that a monocoordinatePd(PtBu 3 ) species was responsible for the C Cl insertion,whereas a bicoordinate Pd(PCy 3 ) 2 species favored C OTfinsertion. However, Schoenebeck has shown subsequently, bytheoretical and experimental studies, that even PtBu 3 canhave a reversal of selectivity for C Cl and C OTf in polarsolvents in the presence of coordinating coupling partners oradditives as a result of the formation of anionic Pd species. [128]A year after his seminal publication, Fu showed theadvantage of using the less-bulky PCy 3 ligand in the couplingof alkyl halides with alkyl or vinyl organoboron reagents. [129]Although B-alkyl-9-BBN systems had been successfullyemployed in coupling with aryl iodides by Suzuki as early as1986, [130] by inclusion of alkyl halide coupling partners, Futook a giant step forward in expanding the substrate scope. Inspite of this work, the analogous transformation utilizingboronic acids continued to represent a challenging goalbecause of competitive b-hydrogen elimination from the alkylpalladium intermediate in the catalytic cycle. This challengeAngew. Chem. Int. Ed. 2012, 51, 5062 – 5085 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org5075