Technical brief

ETA3™ pi-allyl palladium complexes

Simplifying cross-coupling reactions with precatalyst technologies

Palladium catalysed cross-coupling reactions are a ubiquitous methodology in the chemist's toolbox for constructing small molecules with a variety of industrial and human health applications.

Due to the high reactivity and sensitivity of the catalytically active Pd complexes, stable precatalysts that can generate the active Pd catalyst in the reaction mixture are highly desirable. Over the past several decades, many air and moisture-stable precatalyst technologies have been designed to deliver these highly active, low-valent palladium species in a facile and highly efficient manner (Figure 1).

Key benefits

Unmatched ligand scope                                     Enables the wide use of bulky, electron-rich phosphine ligands.

Cleaner activation chemistry                     Produces benign byproducts (ether and alkenes), unlike Buchwald palladacycles.

Superior performance                                     High efficiency and reliability across a broad range of cross-coupling reactions.

History of palladium precatalyst development
Figure 1. Examples of commonly used phosphine-ligated precatalysts.

State-of-the-art ligand technology revolves around bulky, sterically complex, and electron rich monophosphines along with NHC ligands developed by Nolan, Hartwig, Buchwald, Beller, and others. Precatalysts that enable the rapid and efficient formation of active catalysts containing these priveleged ligands offer tremendous value to the chemical industry. Examples of notable precatalyst technologies include NHC-ligated PEPPSI™ precatalysts (Organ), palladacycle precatalysts (Buchwald), and ETA3™ pi-allyl precatalysts. Pi-allyls come in two general types that include NHC ligands (Nolan) and phosphine ligands (Johnson Matthey/Shaughnessy).

Of these various precatalyst technologies, Johnson Matthey's proprietary ETA3™ pi-allyl phosphine precatalysts offer best-in-class ligand scope, quantitative catalyst generation, and superior reactivity for a wide range of cross-coupling applications.

Precatalyst technologies
Figure 2. Modern precatalyst technologies widely used in industrial applications.

ETA3™ pi-allyl precatalysts activate under facile conditions with innocuous byproduct formation

Monoligated Pd(0) complexes are highly reactive catalytic intermediates widely accepted as the key species that drive challenging cross-coupling reactions. A key criterion for the use and efficiency of a given precatalyst technology relies on the activation mechanism that delivers the active monoligated Pd(0) complex as well as the byproducts that result from this activation. Both Buchwald palladacycle and pi-allyl based catalysts are readily activated under basic and nucleophilic conditions.

However, intiation of Buchwald palladacycles forms organic byproducts associated with the aminobiphenyl backbone of the Buchwald scaffold, such as carbazoles and biaryl C-H coupling adducts (1). These byproducts have notable implications for catalyst performance and may generate impurities that are: (1) dependent on the ligand used, (2) challenging to purge downstream, and (3) problematic from a safety or regulatory standpoint. In contrast, activation of ETA3 pi-allyl precatalysts typically results in innocuous ether or alkene byproducts that do not interfere with productive catalysis (2). 

Buchwald Palladacycles
Johnson Matthey ETA3™
Figure 3. Snapshot comparison of Buchwald palladacycle and Johnson Matthey ETA3 precatalyst technologies.

ETA3™ pi-allyl technology enables best in class ligand compatibility and screening flexibility

Johnson Matthey's ETA3 pi-allyl catalyst technology offers the largest and most diverse scope of phosphine ligands when compared to the other precatalyst technologies. Due to the steric constraints around the aminobiphenyl backbone, G3 and G4 Buchwald palladacycles do not form clean, single-component complexes with highly bulky, electron rich biaryl ligands. Also, these complexes can often be air-sensitive or thermally unstable in solution. By comparison, ETA3 precatalysts possess the ability to readily access a cationic metal centre with a dissociated counter anion, opening an additional coordination site around the metal center.

This additional coordination site enables the synthesis of air-stable pi-allyl complexes containing a diverse array of highly bulky and electron rich phosphine ligands (both monodentate and bidentate). Having access to a large library of well-defined precatalysts containing priveleged phosphine ligands can deconvolute variation due to precatalyst activation in high-throughput and miniturised screening workflows.  

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Applications and performance

Scheme 1. Comparison of RuPhos containing precatalysts in the coupling of 4-chloroanisole with morpholine. RuPhos Pd(crotyl)Cl (3) provided superior yields in comparison to all Buchwald palladacycles tested. (3)
Scheme 2. Use of Pd-175 in the synthesis of giredestrant, a selective ER degrader developed by the Roche group. (4)
Scheme 3. Suzuki coupling sequence using Pd-170 in development efforts towards BMS-986378. (5)

Find the right precatalyst for your project or process

The high flexibility of the ETA3 precatalyst platform allows easy integration of new and innovative phosphine ligands into Johnson Matthey's diverse catalyst portfolio. Advanced generation Buchwald ligands designed for challenging amination reactions (EPhos, GPhos, and others) are now available at commercial scale.

Don't see the ligand you are looking for in our catalog below, but want to try our best-in-class precatalyst technology?

Reach out to our team about custom synthesis of ETA3 precatalysts. Our team of experts can also help you choose the ideal catalyst to ensure optimal precious metal recovery in your process. 

ETA3™ catalyst product list

Our ETA3 precatalyst portfolio is available in various formats to meet the needs of your project. We can provide you with individual samples, our pi-allyl kit (includes 13 unique precatalysts), and HTE screening plates for your high throughput testing.
Product number Product description CAS number Mol weight
Pd-110 [PdCl (allyl)]2 12012-95-2 365.89
Pd-161 AmPhos Pd(crotyl)Cl 1334497-06-1 462.35
Pd-162 P(tBu)3 Pd(crotyl)Cl 1334497-00-5 399.29
Pd-170 XPhos Pd(crotyl)Cl 1798782-02-1 673.70
Pd-171 RuPhos Pd(crotyl)Cl 1798781-96-0 663.62
Pd-172 SPhos Pd(crotyl)Cl 1798781-99-3 607.51
Pd-173 [BrettPhos Pd(crotyl)]OTf 1798782-11-2 847.36
Pd-174 [tBuXPhos Pd(allyl)]OTf 1798782-25-8 721.21
Pd-175 [tBuBrettPhos Pd(allyl)]OTf 1798782-02-1 781.26
Pd-176 [(R)-BINAP Pd(allyl)]Cl 879689-47-1 890.56
Pd-177 XantPhos Pd(allyl)Cl 879689-28-8 761.57
Pd-178 PCy3 Pd(crotyl)Cl 307494-95-7 477.41
Pd-180 [BippyPhos Pd(allyl)]OTf 146558-62-0 803.19
Pd-181 P(o-tolyl)3 Pd(crotyl)Cl 1385042-42-1 501.34
Pd-188 CyJohnPhos Pd(crotyl)Cl 692782-19-7 547.46
Pd-189 JohnPhos Pd(crotyl)Cl 1798782-05-4 495.38
Pd-191 [SPhos Pd(allyl)]OTf 1846557-10-5 707.09
Pd-214 [Me4tBuXPhos Pd(allyl)]OTf 1798782-29-2 777.32
Pd-215 [RockPhos Pd(allyl)]OTf 1798782-31-6 756.26
Pd-216 [Me3OMetBuXPhos Pd(allyl)]OTf 2924017-86-5 793.32
Pd-217 CPhos Pd(crotyl)Cl 3105698-81-2 669.65
Pd-218 [EPhos Pd(allyl)]OTf 3105698-83-4 831.37
Pd-219 [GPhos Pd(allyl)]OTf 3105698-85-6 833.34
Pd-220 [AlPhos Pd(allyl)]OTf 3055551-75-9 1111.63
Pd-221 [MorDalPhos Pd(crotyl)]OTf 3105698-87-8 760.20

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References:

  1. 1. ACS Catal. 2025, 15, 21, 18758-18768
  2. 2. ACS Catal. 2015, 5, 9, 5596-5606
  3. 3. J. Org. Chem. 2015, 80, 13, 6794-6813
  4. 4. Org. Process Res. Dev. 2022, 26, 568-582
  5. 5. Org. Process Res. Dev. 2022, 26, 1458-1469