Synergistic Pd/Cu Catalysis in Organic Synthesis

Abstract

Synergistic Pd/Cu catalysis has been utilized in the Sonogashira reaction since 1975. However, this strategy has not received much attention from the organic chemist community until recently. Synergistic Pd/Cu catalysis is becoming a proficient method for the development of catalytic reactions, including several new and efficient cross‐coupling reactions. Additionally, several challenging asymmetric reactions, including stereodivergent synthesis, have been discovered by the combined use of a chiral metal catalyst and a second achiral metal catalyst or two chiral metal catalysts. This review provides an overview of this field, with the aims of highlighting both the development of synergistic Pd/Cu catalysis in organic synthesis and the reaction mechanisms involved in this research area.

Diastereodivergent Synthesis of β‐Amino Alcohols by Dual‐Metal‐Catalyzed Coupling of Alkoxyallenes with Aldimine Esters

“…[23] To test this hypothesis,wec arried out reactions in which Cu(CH 3 CN) 4 PF 6 was replaced with AgOAc,and we were pleased to find that the L3-Ag/L3-Pd catalyst system increased the syn/anti ratio to 12:1, although the yield was slightly low (compare entries 14 and 15 in Table 1). In attempts to improve both the selectivity and the yield, we investigated various solvents (entries [16][17][18][19]. Theb est reaction medium was cyclopentyl methyl ether,w hich gave an 80 %yield of syn-selective coupling product (2S,3R)-4aa with > 99 % ee and 18:1 syn/anti selectivity (entry 19).…”

Copper-Catalyzed C–H Arylation of Fused-Pyrimidinone Derivatives Using Diaryliodonium Salts

“…The absence of base resulted in no detectable product formation (Table 1, entry 11). Decreasing the amount of copper iodide resulted in lower yields and when the catalyst loading is increased, no striking improvement of the yield of the desired product was observed ( Table 1, entries [12][13][14]. The addition of common N-heteroarene ligands such as 1,10-phenanthroline (1,10-Phen) and bipyridine (Bipy) or a phosphorous ligand (Xantphos) did not improve the yield ( 1 Reaction conditions: 1 (1 equiv), 2a (1 equiv), CuX (x mol%), Ligand (30 mol%), tBuOLi (3.5 equiv) was stirred in dioxane (0.37 M) under microwave irradiation at 130 • C for 6 h. 2 NMR yields are calculated using 1,3,5-trimethoxybenzene as internal standard.…”

“…The absence of base resulted in no detectable product formation (Table 1, entry 11). Decreasing the amount of copper iodide resulted in lower yields and when the catalyst loading is increased, no striking improvement of the yield of the desired product was observed ( Table 1, entries [12][13][14]. The addition of common N-heteroarene ligands such as 1,10-phenanthroline (1,10-Phen) and bipyridine (Bipy) or a phosphorous ligand (Xantphos) did not improve the yield (Table 1, entries [15][16][17][18][19][20].…”

“…This expanding methodology's main feature is the introduction of structural diversity into complex molecules having multiple Csp2-H bonds [4][5][6][7][8]. Our group has previously reported the selective palladium-catalyzed and copper assisted C2-H arylation of quinazolin-4-ones, pyrido-pyrimidin-4-ones (see (a) in Scheme 1a) and thiazolo [5,4-f ]quinazolin-9(8H)-one under microwave irradiation (Scheme 1b) [9][10][11][12][13][14]. This aforementioned heterocycle was used as a versatile scaffold for Structure Activity Relationship (SAR) studies in DYRK1A kinase inhibition involved in the field of neurodegenerative diseases [15][16][17] and cancer therapy [18][19][20].…”

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

“…In traditional Sonogashira cross-coupling reactions, a catalytic amount of a transition metal (generally Pd) is used in combination with a copper salt co-catalyst. This way, the classical Sonogashira reaction promotes the C–C bond formation between terminal alkynes and aryl (or vinyl) halides via a dual Pd/Cu catalysis [ 109 – 110 ]. The general mechanism of this initially reported C–H functionalization protocol is illustrated in Fig.…”