Chemistry Reference
In-Depth Information
5
Alkene and Alkyne Insertion Reactions
5.1 The Heck Reaction
The Heck reaction (or Mizoroki-Heck reaction) is an alkene transformation involving the insertion of an
alkene into a carbon-palladium single bond (Scheme 5.1).
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The alkene employed is often electron poor, but
this is not a requirement. In synthetic planning, it is an alternative for the Wittig reaction in some cases,
but uses a starting material with one carbon fewer. While the original Heck reaction appears to be a simple,
but useful, transformation, it has become a powerful synthetic reaction. The mechanism involves oxidative
addition of the halide
5.1
to the palladium(0) species to generate an organopalladium(II) intermediate
5.4
.
Alkene coordination and insertion generates a new organopalladium(II) intermediate
5.7
which undergoes
-hydride elimination. The product
5.3
dissociates from the palladium, leaving a palladium(II) hydrohalide
5.10
that reacts with the base to regenerate the palladium(0) catalytic species. Ligand association and
dissociation occurs at a number of points in the mechanism. Consequently, the amount of ligand, which
is usually a phosphine, is a key variable. Excess ligand inhibits, and even shuts down, the reaction as the
operation of Le Chatelier's principle prevents the formation of any sufficient concentration of an active,
coordinatively unsaturated, palladium species. Conversely, if too little ligand is present, the palladium may
become totally uncoordinated. In this case, the palladium usually deposits itself in metallic form on the inner
surface of the flask as a palladium mirror and is catalytically inactive. A fixed rule for the ligand:catalyst ratio
cannot be given and this must be determined empirically. In general, when the substrate is an iodide, less
ligand is required as the liberated iodide can act as a ligand. The solvent may also act as a ligand. Solvents
such as toluene are very poor ligands, while acetonitrile is a good ligand. The amount of added phosphine
ligand required will, therefore, differ according to solvent properties.
5.1.1 The Organic Halide
Iodobenzene is the example given above. For the organic part, aryl, including heteroaryl,
2
and vinyl groups
can be used (Schemes 5.2-5.4). The reaction between 3-bromopyridine and the
N
-phthaloyl substituted alkene
allowed a short synthesis of nornicotine (Scheme 5.5). Alkynyl halides have been infrequently employed.
3
If an alkyl group is used, oxidative addition is slow and
-hydride elimination will occur, as in coupling
reactions. Steric hindrance around the halide will slow the reaction down. The presence of a good donor
group, such as a carboxylic acid, in the
ortho
position of an aryl halide will also inhibit the Heck reaction, as
chelation of the palladium will block coordination of the alkene substrate.
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