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

Palladium-Catalyzed Cross-CouplingAngewandteChemieScheme 17. The Suzuki–Miyaura cross-coupling reaction. [89]into the catalytic realm, now known as the Suzuki–Miyauracoupling (see Figure 2).In a vast understatement, we note that the Suzuki–Miyaura reaction has developed into an extremely powerfuland general method for the formation of C C bonds, [91]displaying a number of advantageous features: 1) easilyhandled and usually air- and moisture-stable organoboronstarting materials; 2) mild and convenient reaction conditionsand 3) the facile removal of less-toxic inorganic byproducts.These aspects make the Suzuki–Miyaura coupling reactionespecially useful for industrial applications.In later years, modification of the organoboron reagenthas led to the development of milder and more selectiveSuzuki–Miyaura couplings, among which the GenÞt/Molander BF 3 K salts [92,93] and the Burke MIDA (N-methyliminodiaceticacid) boronates [94] are the most prominent.Recently Knochel introduced magnesium di-(hetero)arylboronates and magnesium di(alkenyl)boronatesas a new class of Suzuki reagent by treating the organichalides with B(OBu) 3 with Mg in the presence of LiCl. [95]Often the exact nature of the organoboron species can haveprofound effects on the efficacy of a given transformation.Indeed, the mixed aqueous/organic solvent systems normallyemployed in Suzuki–Miyaura reactions may lead, not only toprotodeboronation as a function of electronic and stericnature of the substrate, but can affect the nature of the boronreagent itself (boronic acid, half-acid ester, boroxine, borinicacid). The associated purity issue is often an unknown factorsince its characterization is not usually carried out, and maycause difficulty in interpreting failed Suzuki–Miyaura couplingreactions, especially when boronates are employed.An important consideration in the Suzuki–Miyaura reactionis the base employed. Perhaps the earliest, mostdistinguished, example originates from Kishis investigationof the effect of base in a reaction en route to the totalsynthesis of Palytoxin (Scheme 18). [96] In this work, the use ofthallium hydroxide as base makes the reaction complete,essentially on mixing of the reagents. Although effects maynot be as dramatic as this on a routine basis, such exampleshave elegantly shown the importance of base source as well asthe synthetic power of the Suzuki–Miyaura reaction.A hallmark of the Suzuki discovery was the demonstrationthat “activation” of the organometallic component as theboronate (sometimes referred to as the “ate” complex) wouldallow the coupling of organometallic reagents unable toundergo transmetalation under standard conditions. Thisdiscovery pointed to the possibility of uncovering couplingreactions of other organometallics with lower electronegativitydifferences between the metal and the organic moiety. [97] Itwould be a decade before such reactivity was revealed ina new class of organoelement compounds.Scheme 18. Kishi’s studies on the importance of base in the Suzuki–Miyaura coupling. [96]2.3.4. The Hiyama Reaction (1988–1994): OrganosiliconCoupling PartnersIn 1982, Kumada reported the use of organopentafluorosilicatesin palladium-catalyzed cross-coupling reactions. [98]In the same year, Hallberg disclosed the coupling of vinyltrimethylsilane.[99] Building on these reports, in 1988 Hiyamaand co-workers described the palladium- and nickel-catalyzedcoupling of organosilanes with aryl halides and triflatesactivated by the inclusion of a fluoride source in the reaction[100, 101]mixture (Scheme 19). Thus tris(dimethylamino)sulfoniumdifluorotrimethylsilicate (TASF) [100] or CsF [102] wasshown to be required to activate the organosilane towardstransmetalation by the formation of silicate intermediates.The Hiyama coupling provided a more environmentallyfriendly and safe option than the organoboron, organozinc,and organostannane reagents. This discovery has beenpursued on other silicon derivatives, for example, siloxanesby Denmark [103] and DeShong, [104] among others, whichanticipates the promise of greater prominence of theHiyama coupling reaction in the near future.Scheme 19. The Hiyama cross-coupling reaction. [100,103]2.4. Carbon–Heteroatom Coupling ReactionsUp to this point in the historical development of crosscoupling,a stoichiometric organometallic partner had generallybeen required to achieve efficient cross-coupling, theexception being the Mizoroki–Heck reaction. Other functionalpartners, with a few exceptions, (e.g. R 3 Si SiR 3 ,R 3 SnSnR 3 ) were unsuitable for functionalization of organic sub-Angew. Chem. Int. Ed. 2012, 51, 5062 – 5085 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org5073