Mechanistic Aspects of Metal‐Catalyzed C,C‐ and C,X‐Bond Forming Reactions

Abstract

Cross-coupling reactions comprise a group of transformations for the formation of C–C bonds based on the transmetallation of nucleophilic organometallic compounds with organic electrophiles in the presence of late-transition metals as catalysts [1]. In most cases, cross-coupling reactions are based on palladium(0) catalysis [2–7], although nickel catalysts were actually involved in the initial discovery of cross-coupling methods by Kumada et al. [8] and are currently receiving renewed attention [9]. These transformations were later extended to the use of heteronucleophiles, such as amines, alcohols, and thiols, for the formation of C-X bonds. The first palladium-catalyzed cross-coupling reactions of organostannanes were reported in the 1976–1978 period by the groups of Eaborn [10], Kosugi et al. [11], and Stille [12]. This transformation is usually known as the Stille coupling [13–17] and, together with the Suzuki–Miyaura cross-coupling of organoboron compounds [18–21], has been established as themost general and selective palladium-catalyzed cross-coupling reaction [1, 22–24] (Scheme 1.1). Synthetically, the Stille reaction takes prevalence over the Suzuki–Miyaura coupling in substrates bearing a stannane and a boronic ester as reactive sites [25]. Mechanistically, these reactions are closely related to other transmetallation-based cross-couplings of organometallic nucleophiles [26] such as the Negishi [27, 28], Hiyama [29, 30], Sonogashira [31, 32], Kumada (or Kumada–Corriu), and other related couplings [33–36]. The first thorough mechanistic studies centered on the Stille reaction [13, 14]. Although some important differences exist between this reaction and related crosscouplings, the main mechanistic conclusions that arose from work done on this reaction pertain to other related cross-couplings proceeding through Pd(0)/Pd(II) catalytic cycles. Although nickel, copper, iron, cobalt, and occasionally platinum have also been used as catalysts for cross-coupling processes, most of the detailed mechanistic studies concern palladium chemistry. Cross-coupling reactions share important mechanistic details with the Heck alkenylation of organic electrophiles [37, 38]. Indeed, the 2009 Nobel Prize for chemistry recognized both the Heck