Pd-catalyzed Suzuki cross-coupling

Scheme 5.2-18 Pd-catalyzed Suzuki cross-coupling reaction in a [BMIM][BF4] ionic liquid.

Pd-catalyzed Suzuki cross-coupling Pd-catalyzed coupling between organoboron compounds and organic halides and triflates. 448... 

Littke, A. F., Fu, G. C. A convenient and general method for Pd-catalyzed Suzuki cross-couplings of aryl chlorides and arylboronic acids. Angew. Chem., Int. Ed. Engl. 1999, 37, 3387-3388. 

The Suzuki reaction of halo-pyrimidines with organoboron derivatives is not limited to Csp2—Csp2 coupling, but can also be accomplished in a Csp —( sp- fashion. Hydroboration of terminal alkene 107 with 9-BBN followed by Pd-catalyzed Suzuki cross coupling with 5-bromopyrimidine provides the desired alkyl substituted product 108. The classical Suzuki conditions proved insufficient, whereas the combination of Pd(OAc)2 and a biphenyl monophosphine ligand developed by Buchwald provided the desired product in 55% yield [45]. 

Recent work has led to the use of bulk electron-rich phosphine ligands to facilitate palladium-catalyzed processes with problematic oxidative addition. For examples, see (a) Littke, A.F. Fu, G.C. A convenient and general method for Pd-catalyzed Suzuki cross-couplings of aryl chlorides and arylboronic acids. Angew. Chem., Int. Ed. Engl. 1998, 37, 3387-3388. (b) Shen, W. Palladium catalyzed coupling of aryl chlorides with arylboronic acids. Tetrahedron Eett. 1997, 38, 5575-5578. (c) Old, D.W. Wolfe,... 

Scheme 3.82 Preparation and Pd-catalyzed Suzuki cross-coupling of functionalized alkyl trifluoroborates.

During a study of Pd/P(t-Bu)2Me-catalyzed Suzuki cross-couplings of primary alkyl bromides with boronic acids, Fu examined the stoichiometric reaction of Pd(P(t-Bu)2Me)2 with an alkyl bromide (Eq. 16) [17]. Interestingly, not only was oxidative addition facile at 0 °C, but the adduct (4) could be isolated in excellent yield and even crystallographically characterized. 

Pd-biscarbene complexes (Figure 19) catalyzed Suzuki cross-coupling reactions of halobenzenes including chlorobenzenes with phenylboronic acid were achieved at room temperature in [G4G4lm]BF4 with MeOH as co-solvent under ultrasonic irradiation. " ... 

Hong FE, Chang YL et al (2004) Preparation and NMR studies of cobalt-containing diphosphine ligand chelated W, Ru, Au and Pd complexes Suzuki cross-coupling reactions and carbonylation catalyzed by the Pd complex. Dalton Trans 157-165... 

Figure 3.56. Scope of Pd/63-catalyzed as5mmetric Suzuki cross-coupling of naphthyl bromides with arylboronic acids.

Chemists working to develop new bioactive compounds try to be alert for new stable heterocycle platforms, but they can easily overlook some of the more, shall we say, exotic ones. When one thinks about the utility of boron in heterocyclic chemistry, the Suzuki cross-coupling reaction typically first comes to mind. In this valuable synthetic reaction <95CRV2457>, a boronic acid group is discarded under basic conditions during a Pd-catalyzed C-C bond formation. There are exceptions, of course, but few chemists appreciate that boron is an element that can be valuable to retain in a molecule so that its unique properties can be utilized. 

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