Pd‐Catalyzed Cross‐Coupling with Organometals Containing Zn, Al, Zr, and so on – The Negishi Coupling and Its Recent Advances

Abstract

The Pd-or Ni-catalyzed cross-coupling reactions of organometals containing Zn, Al, Zr, and B as well as related reactions of those containing Mg and several other metals collectively have emerged as arguably the most widely applicable organic skeleton construction method discovered and developed over the past several decades, allowing synthetic chemists to prepare practically all types of organic compounds. In this chapter, some of the seminal and critically important discoveries and early developments in the 1970s as well as their current scope are briefly discussed. Some of the notable discoveries and developments include (i) identification of superior properties of Pd as a critical element for crosscoupling relative to Ni, (ii) the broad scope of Pd-or Ni-catalyzed cross-coupling with respect to metal countercations including Zn, Al, Zr, B, and Mg, (iii) the hydrometallation-Pd-catalyzed cross-coupling sequential processes for selective syntheses of alkenes, dienes, oligoenes, and oligoenynes, (iv) double metal catalysis involving Pd or Ni and added metal compounds containing Zn, In, Li, and others, and (v) realization of high turnover numbers (TONs) (≥10 3 -10 9 ) through the use of chelating phosphines, such as bis-[2-(diphenylphosphino)phenyl] ether (DPEphos) and 1,1 -Bis(diphenylphosphino)ferrocene (dppf).The Zr-catalyzed alkyne carboalumination and the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) have provided efficient and selective routes to (E)-trisubstituted alkenylalanes and 2-substituted chiral alkylalanes, respectively. These reactions provide two additional examples of prototypical transition metal-catalyzed organometallic reactions. Significantly, they can be readily combined with the Pd-or Ni-catalyzed cross-coupling for the synthesis of trisubstituted alkenes embracing a wide variety of natural products, such as terpenoids, carotenoids, and others, as well as various chiral organics including deoxypolypropionates and saturated terpenoids. The Zr-catalyzed alkyne carboalumination has been applied to the synthesis of a large number (>100) of natural products, while the ZACA reaction has been transformed from a mere scientific novelty to a full-fledged asymmetric synthetic method that is catalytic in both transition metal (Zr) and chiral auxiliaries through a series of breakthroughs.

Nickel‐Catalyzed Alkyl–Alkyl Cross‐Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent

“…[12] Several years ago, we reported a nickel/pybox-based method for coupling unactivated secondary alkyl bromides with alkylzinc reagents in good yield [Eq. (3)].…”

Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides

“…Alkenylzirconium reagents have proved to be useful nucleophiles in metal-catalyzed couplings, 30 due in part to their readily availability (reaction of commercially available Schwartz’s reagent with alkynes), their ability to transmetalate to a catalyst under mild conditions without the need for a Lewis-basic activator (in contrast to typical Suzuki and Hiyama reactions), and their good functional group compatibility. Upon investigating an array of parameters, we determined that a chiral nickel/pyridine-oxazoline catalyst can achieve the enantioconvergent coupling of a racemic tertiary α -halocarbonyl compound with an alkenylzirconium reagent with very good yield and enantioselectivity at room temperature ( Table 1 , entry 1); both NiCl 2 ·glyme and the chiral ligand ( L1 ) are commercially available.…”

Silylative coupling of olefins with vinylsilanes in the synthesis of functionalized alkenes

“…1,2 Spectacular examples of selective reactions of organometallic compounds with organic electrophiles that have been permanently accepted in the canon of modern organic synthesis, are the catalytic coupling processes: Suzuki-Miyaura (boron compounds), 3 Stille (tin compounds), 4 Negishi (zinc compounds) 5 and Hiyama (silicon compounds). 1,2 Spectacular examples of selective reactions of organometallic compounds with organic electrophiles that have been permanently accepted in the canon of modern organic synthesis, are the catalytic coupling processes: Suzuki-Miyaura (boron compounds), 3 Stille (tin compounds), 4 Negishi (zinc compounds) 5 and Hiyama (silicon compounds).…”