Page 747 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Ar Pd Ar 723

H SECTION 8.2
Reactions Involving
Organopalladium
syn-arylpalladation syn-β–elimination Intermediates

Entry 5 illustrates use of a vinyl triflate under the “phosphine-free” conditions. Entry 6
achieved exceptionally high catalyst efficiency by using a palladacycle-type catalyst.
Entries 7 and 8 show the introduction of acrylate ester groups using functionalized
alkenyl iodides. Entry 9 demonstrates two successive Heck reactions employed in a
large-scale synthesis of a potential thromboxane receptor antagonist. These reactions
were carried out in the absence of any phosphine ligand. The greater reactivity of the
iodide over the bromide permits the sequential introduction of the two substituents.
There are numerous examples of intramolecular Heck reactions, 151 such as in
Entries 10 to 14. Entry 11 is part of a synthesis of the antitumor agent camptothecin.
The Heck reaction gives an 11:1 endocyclic-exocyclic mixture. Entries 12–14 are also
steps in syntheses of biologically active substances. Entry 12 is part of a synthesis of
maritidine, an alkaloid with cytotoxic properties; the reaction in Entry 13 is on a route
to galanthamine, a potential candidate for treatment of Alzheimer’s disease; and Entry
14 is a key step in the synthesis of a potent antitumor agent isolated from a marine
organism.

8.2.3. Palladium-Catalyzed Cross Coupling

Palladium can catalyze carbon-carbon bond formation between aryl or vinyl
halides and sulfonates and a wide range of organometallic reagents in cross-coupling
reactions. 152 The organometallic reagents used include organolithium, organomag-
nesium, and organozinc reagents, as well as cuprates, stannanes, and organoboron
2
2
2
compounds. The reaction is quite general for formation of sp -sp and sp -sp bonds
in biaryls, dienes, polyenes, and enynes. There are also some reactions that can couple
alkyl organometallic reagents, but these are less general because of the tendency of
alkylpalladium intermediates to decompose by -elimination. Arylation of enolates
also can be effected by palladium catalysts.
The basic steps in the cross-coupling reaction include oxidative addition of the
aryl or vinyl halide (or sulfonate) to Pd(0), followed by transfer of an organic group
from the organometallic to the resulting Pd(II) intermediate (transmetallation). The
disubstituted Pd(II) intermediate then undergoes reductive elimination, which gives
the product by carbon bond formation and regenerates the catalytically active Pd(0)
oxidation level.
oxidative addition R X + Pd 0 R Pd II X

transmetallation R Pd II X + R′ M R Pd II R′ + M X

reductive elimination R Pd II R′ R R′ + Pd 0

151 J. Link, Org. React., 60, 157 (2002).
152
F. Diederich and P. J. Stang, Metal-Catalyzed Cross-Coupling Reactions, Wiley-VCH, New York, 1998;
S. P. Stanforth, Tetrahedron, 54, 263 (1998).