New Palladium Precatalyst Technology Developed by the Hazari Group at Yale University Now Available from Strem Chemicals UK Ltd

New Palladium Precatalyst Technology Developed by the Hazari Group at Yale University Now Available from Strem Chemicals UK Ltd

Palladium Precatalysts with Indenyl Ligand for C-C and C-N Bond Formation

Strem Chemicals is pleased to introduce a new product line of palladium precatalysts for cross-coupling reactions, developed by Nilay Hazari’s group (Yale University).1 Hazari and co-workers’ technology utilizes t-butylindenyl as a replacement for the commonly used ƞ3-allyl-ligand to form a [ƞ3-1- t-butylindenylPdCl] dimer (46-0868).  The dimer can be readily converted into monomers through treatment either with NHC (46-0815) or phosphine ligands (see 46-0435, 46-0437 and 46-0440) to generate palladium precatalysts which display high reactivity in cross-coupling reactions.

Palladium catalysts play an ever more important role in organic synthesis for both academic and industrial applications. Traditionally, the palladium source and the desired ligand were added separately to the reaction mixture to form the active catalyst in situ.  In recent years, palladium precatalysts have become more desirable due to their stability and ease of use.  In these precatalysts, the palladium is already attached to the ligand of choice, with additional components to stabilize the scaffold.

Prominent examples of this concept are the Buchwald palladacycles with the most recent examples involving a 2-aminobiphenyl ligand forming a complex with a Pd(II) center, a phosphine ligand and a counter ion.  The resulting stable complexes can be stored for extended periods of time, handled in air, and display high reactivity in desired reactions.

Steve Nolan followed a similar approach by preparing precatalysts consisting of a Pd(II) center bound to a NHC-ligand, an ƞ3-allyl ligand, and a chloride ligand.

The Hazari groups’ technology utilizes the very bulky 1-t-Bu-indenyl ligand as a surrogate for an ƞ3-allyl ligand. The Pd center is located perpendicular to the plane of the t-Bu-indenyl ligand. The Pd is not centered in the middle of the five-membered ring  of the indene ligand (which indicates  ƞ5-bonding), but is slightly off center and only interacts with the three carbon atoms that are not part of the six-membered ring (see structures for 46-0868 and 46-0815 above).  Starting with the dimer 46-0868, a plethora of different NHC and phosphine ligands can be ligated to rapidly generate a series of Pd precatalysts. This provides organic chemists with the ability to easily screen electronically and sterically diverse ligands. The IPr supported precatalyst 46-0815 has been shown to be superior in Suzuki-Miyaura reactions, while phosphine supported systems, such as 46-0435, are excellent for a range of processes including (i) Suzuki-Miyaura  reactions involving heteroaryl boronic acids, (ii) Suzuki-Miyaura reactions involving alkyl trifluoroboronate salts, (iii) Suzuki-Miyaura reactions involving aryl chlorides with unprotected imidazoles and pyrazoles, (iv) Buchwald-Hartwig reactions with sterically congested secondary amines; and (v) a-arylation reactions with heteroaryl ketones.

Reference:

  1. Melvin, P. R.; Nova, A.; Balcells, D.; Dai, W.; Hazari, N.; Hruszkewycz, D. P.; Shah, H. P.; Tudge, M. T. ACS Catal. 2015, 5, 3680-3688.

 

Products mentioned in this blog:

46-0435: Chloro(1-t-butylindenyl)[2-(dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl]palladium(II)
46-0437: Chloro(1-t-butylindenyl)[2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl]palladium(II)
46-0440: Chloro(1-t-butylindenyl)[2-(dicyclohexylphosphino)-2′,6′-di-i-propoxy-1,1′-biphenyl]palladium(II)
46-0815: Chloro(1-t-butylindenyl)[1,3-bis(2,6-di-i-propylphenyl)imidazol-2-yl]palladium(II), 98%
46-0868: Chloro(1-t-butylindenyl)palladium(II) dimer, 98%