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Experiment 4, page 1

Department ofChemistry, Imperial College
Third YearAdvanced Practical Organic Chemistry

EXPERIMENT 4:
PALLADIUM CATALYSED CROSS COUPLING REACTIONS

Aims of the experiment
To prepare a diarylalkyne from an aryl halide and monosubstituted alkyne using palladium catalysis.

Techniques used/learned:
Transition metal catalysis; preparative vacuum sublimation for the isolation of the product.

Introduction
Transition metal mediated reactions are becoming increasingly important in organic synthesis as organic chemists become familiar with the myriad of organometallic mechanisms involved in these processes.¹
Palladium is by far the most developed and used as far as application to organic synthesis is concerned²and indeed homogeneous palladium catalysts are used in the commercial production of acetaldehyde, cinnamates and other products. Palladium undergoes many reactions with organic systems and, apart from the well known hydrogenation and oxidation (Wacker and other²) processes, it acts as a catalyst for many key C--C bond forming reactions.
Three areas are particularly important: the reaction of p-allyl-(h³-allyl)palladium cations with nucleophiles, the cross coupling of organometallic reagents (such as organotin, organoboron and organozinc reagents) with organic halides, and the reaction of organic halides (usually aryl/alkenyl halides) with olefins - the Heck reaction. The first of these was extensively developed by Trost,³ the second by Kumada⁴and later by Stille,⁵Suzuki⁶and others and the last by Heck himself.⁷The catalytically active component in these reactions is frequently a Pd(0) species. However, the added material is often a Pd(II) salt as in these cases the Pd(0) is generated in situby reduction with the organometal reagent, solvent or some other species in the reaction mixture.
A full account of this fascinating and widely usedarea of chemistry, including the generally accepted mechanisms, can be culled from the references cited (1-7). It is important to note that the ready oxidative addition of the aryl halides and triflates to the Pd(0) species reverses the conventional concepts of reactivity in aryl systems: in nucleophilic displacement processes, as normally encountered, the alkyl halides are the more reactive. In the palladium catalysed reactions, the alkyl halides are the unreactive species.
In this experiment, 4-nitrobromobenzene is cross coupled with phenylacetylene to give the mixed diarylalkyne. The product is conveniently purified by vacuum sublimation, a clean and much underused technique.

^{+ Pd(OAc)2}

O₂N^PPh3,Et3N
O
2^N