The Recent Development of Phosphine Ligands Derived from 2-Phosphino-Substituted Heterocycles and Their Applications in Palladium-Catalyzed Cross-Coupling Reactions

Abstract

Heterocyclic phosphines have long been used as unique and efficient ligands for palladium-catalyzed cross-coupling reactions. The simplest ligand, trifurylphosphine, has become one of the most classical heterocyclic phosphines for coupling reactions since its first application in the Stille coupling reaction in 1988. In recent decades, palladium catalyst systems derived from highly diverse and innovative heterocyclic phosphines have shown excellent catalytic activities in cross-coupling reactions. In this account, we discuss the recent development and applications of heterocyclic phosphine ligands, highlighting the synthetic pathways used to prepare the ligands. The sections are categorized by the different palladium-catalyzed cross-coupling methodologies.

Synthesis of 3-aryl-1-phosphinoimidazo[1,5-a]pyridine ligands for use in Suzuki–Miyaura cross-coupling reactions

“…7,8 Monophosphine ligands have found widespread use in metal-catalyzed cross-coupling reactions. [9][10][11][12][13] Privileged ligands such as Buchwald's biarylphosphines, [14][15][16][17] Stradiotto's biaryl P-N phosphines, [18][19][20][21] Fu/Koie/Shaughnessy's trialkylphosphines, 7,8,22 Hartwig's ferrocenes, 23,24 Ackermann's diaminochlorophosphines, 25,26 Beller's bis(adamantyl)phosphines 27 and N-aryl(benz)imidazolyl-or N-pyrrolyl-monophosphines, [28][29][30] Kwong's indolyl-based monophosphines, [31][32][33][34][35] Zhang's ClickPhos ligands, 36,37 Singer's bippyPhos ligands, 38,39 Rodriguez/Tang's oxaphospholes, 40,41 and Verkade's proazaphosphatranes 42,43 have found wide-spread use in Suzuki-Miyaura, Corriu-Kumada, Heck, Negishi, Sonagashira, carbon-heteroatom cross-coupling and Buchwald-Hartwig amination reactions (Fig. 1).…”

When cross-coupling partners meet indolylphosphines

“…This method has many advantages as the reaction conditions offer excellent functional group compatibility and the coupling partners (arylboronic acids) are of low toxicity as well as high commercial availability. Aryl iodides, bromides, and more recently chlorides [12,18], tosylates and mesylates [11] are applicable electrophiles this biaryl synthesis.…”

“…Walsh and co-workers reported the first Pd-catalyzed direct α-arylation of unactivated sulfoxides with aryl halides [57]. A variety of aryl methyl sulfoxides were successfully coupled with aryl bromides under the Pd(OAc) 2 /NPCy o-Toldole-phos (L2c) system (Table 7, entries [11][12][13][14]. It is notable that more challenging alkyl methyl sulfoxides and aryl chlorides were also proved to be successful coupling partners (Table 7, entry 15) when Buchwald-type second-generation dimeric precatalyst was employed ( Figure 2) [58].…”

“…Recent ligand exploration showed that indolylphosphines are highly efficient toward various palladium-catalyzed coupling reactions, such as Suzuki-Miyaura coupling, Sonogashira coupling, Hiyama coupling, Buchwald-Hartwig amination, cyanation, C-H functionalization and borylation. (Table 1) [11,12]. It is significant to understand how the catalyst performs through varying the structure of ligands.…”

An Asymmetric Variant of the Bischler–Möhlau Indole Synthesis

“…[20,21] They form the basis of several interesting materials [22] and are employed in the preparation of various ligands. [23][24][25][26] There are numerous routes to substituted indoles and these have been classified in several comprehensive reviews. [27][28][29] Planar chiral indoles are uncommon.…”