Well-defined nickel and palladium precatalysts for cross-coupling

Abstract

Transition metal-catalysed cross-coupling is one of the most powerful synthetic methods and has led to vast improvements in the synthesis of pharmaceuticals, agrochemicals and precursors for materials chemistry. A major advance in cross-coupling over the past 20 years is the utilization of well-defined, bench-stable Pd and Ni precatalysts that do not require the addition of free ancillary ligand, which can hinder catalysis by occupying open coordination sites on the metal. The development of precatalysts has resulted in new reactions and expanded substrate scopes, enabling transformations under milder conditions and with lower catalyst loadings. This Review highlights recent advances in the development of Pd and Ni precatalysts for cross-coupling, and provides a critical comparison between the state of the art in Pd- and Ni-based systems.

Figure 1. Recent developments in palladacycle and PEPPSI precatalysts

a | The evolution of Buchwald palladacycle precatalysts from the 1st to the 4th generation. b | The activation of 4th generation Buchwald palladacycle precatalysts involves reductive elimination of a substituted carbazole and formation of an active Pd(0) species. c | Coordination of supporting ligands to dipalladium(ii) species affords Buchwald palladacycle precatalysts. d | Examples of sterically bulky phosphines typically incorporated into 3rd and 4th generation Buchwald palladacycle precatalysts. e | The Pyridine- Enhanced Precatalyst Preparation Stabilization and Initiation (PEPPSI) paradigm for Pd(ii) precatalysts developed by Organ. f | Examples of thioether formation mediated by Organ’s PEPPSI-based precatalysts.

Figure 2. A summary of recent improvements to η³-allyl-type precatalysts

a | Original allyl-type precatalyst from Nolan and more efficient related precatalysts from Johnson Matthey and Yale. b | Selection of N-heterocyclic carbene (NHC) ligands that are compatible with allyl-type precatalysts. c | Pathway for the activation of allyl-type precatalysts, showing competition between unproductive Pdⁱ dimer formation and entry into the catalytic cycle. d | Examples of cross-coupling reactions catalysed by Yale precatalysts.

Figure 3. Proposed catalytic pathways for bridging halide Pd(i) precatalysts and structural evidence for new Pd(0) precatalysts

a | Structures of [(P^tBu₃)₂Pd₂(μ-X)₂] (X = Br or I) precatalysts. b | Catalytic cycle for cross-coupling reactions catalysed by [(P^tBu₃)₂Pd₂(μ-I)₂] in the presence of weak nucleophiles. c | The catalytic cycle operative when strong nucleophiles are used. d | Generic representation of Buchwald Pd(0) precatalysts. e | X-ray crystal structure of [(AlPhos)₂Pd₂(μ-COD)] (COD = 1,5-cyclooctadiene); the hydrogen atoms are omitted for clarity.

Figure 4. Types of electrophiles and nucleophiles that can be coupled with Ni precatalysts of the form [L_nNiX₂]

Note that [(PPh₃)₂NiCl₂] can exist in either square planar or tetrahedral isomeric forms. Also, given that [(dtbbpy)NiBr₂] (dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine) is primarily used in cross-electrophile coupling, we do not give any nucleophiles for its reactions.

Figure 5. Structures of common Ni precatalysts based on oxidation state and supporting ligands

a | Precatalysts of the form [L_nNi(Ar)X] can feature neutral C-, N- and P-donor ligands. b | The precatalysts [L_nNi(allyl)X] feature N-heterocyclic carbene (NHC) ligands and are active in a wide array of reactions. c | Common Ni(i) precatalysts are either three- or four-coordinate and feature one anionic ligand. d | Common Ni(0) precatalysts feature neutral, soft π-acceptor ligands.