Highly Active Palladium Catalysts for Suzuki Coupling Reactions

Abstract

Mixtures of palladium acetate and o-(di-tert-butylphosphino)biphenyl (4) catalyze the room-temperature Suzuki coupling of aryl bromides and aryl chlorides with 0.5−1.0 mol % Pd. Use of o-(dicyclohexylphosphino)biphenyl (2) allows Suzuki couplings to be carried out at low catalyst loadings (0.000001−0.02 mol % Pd). The process tolerates a broad range of functional groups and substrate combinations including the use of sterically hindered substrates. This is the most active catalyst system in terms of reaction temperature, turnover number, and steric tolerance which has been reported to date.

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“…67 Since 1998, the use of supporting 1-di(cyclo)alkylphosphinobiphenyl ligands for the palladium-catalysed Suzuki reaction of aryl chlorides and aryl arenesulfonates has been intensively investigated by the research group of Buchwald. [68][69][70][71][72][73][74] The structures of some of these ligands are reported in Figure 3. In particular, phosphine 26 proved to be a very effective supporting ligand for the room-temperature palladium-catalysed Suzuki reaction of both electron-rich and electron-deficient aryl chlorides.…”

“…68 Further studies involving ligands 27-29 revealed that catalysts supported by 29 were more efficient than those supported by 26 and catalysed the room-temperature Suzuki coupling of aryl bromides and chlorides with 0.5-1.0 mol% Pd. 69,70 The use of 27 as a ligand was successful for the Suzuki coupling of hindered substrates and allowed these reactions to be carried out at low precatalyst loadings (0.000001-0.02 mol Pd) 70 and catalysts employing ligands 26, 27, 30 and 31 functioned well for the synthesis of biaryls containing more than one ortho-substituent. 70 On the other hand, a catalyst system composed of a mixture of ligand 26 and Pd on carbon was successfully used for the preparation of enantiopure mandelic acids 75 and a mixture of Pd 2 (dba) 3 and the binaphthyl ligand (S)-(+)-34 proved to be effective for the synthesis of axially chiral biaryl compounds in up to 92% ee.…”

“…69,70 The use of 27 as a ligand was successful for the Suzuki coupling of hindered substrates and allowed these reactions to be carried out at low precatalyst loadings (0.000001-0.02 mol Pd) 70 and catalysts employing ligands 26, 27, 30 and 31 functioned well for the synthesis of biaryls containing more than one ortho-substituent. 70 On the other hand, a catalyst system composed of a mixture of ligand 26 and Pd on carbon was successfully used for the preparation of enantiopure mandelic acids 75 and a mixture of Pd 2 (dba) 3 and the binaphthyl ligand (S)-(+)-34 proved to be effective for the synthesis of axially chiral biaryl compounds in up to 92% ee. 71 Buchwald et al 72 also reported that a variety of tetraortho-substituted biaryls can be synthesised in 55-98% yield by Suzuki palladium-catalyzed cross-coupling reactions in which doubly ortho-substitued phosphine 32a was used as a supporting ligand.…”

“…The use of these precatalysts can overcome the problems pertaining to the Suzuki cross-coupling reactions where expensive palladium complexes, which are difficult to prepare and recover, are used as catalyst precursors. Nevertheless, it should be mentioned that although the ligandless palladium precatalysts often achieve significantly fast cross-couplings in aqueous media, complete conversion is not always possi- 66,70,185,192 Nevertheless, despite these important results, a number of challenges, especially with regard to industrial applications of the Suzuki coupling reactions, remain. In fact, even though some successful results in the preparation and use of efficient heterogeneous catalyst systems have been obtained, it is still necessary to develop much more effective and low-cost heterogeneous catalysts which are able to work in very mild conditions.…”

Aminophosphine Palladium Pincer Complexes for Suzuki and Heck Reactions

“…[4][5][6][7][8][9][10][11][12] Most of these palladium catalysts suffer from other drawbacks as well, such as poor thermal stability as well as poor stability towards oxygen and water, a major problem especially for catalysts employed in the Heck cross-coupling reaction because a typical protocol for this reaction still requires prolonged reaction times at high temperatures in combination with relatively high catalyst loadings -all factors promoting the formation of palladium black and thereby leading to inactivation of the active species.…”