Carbohydrate-Derived Ligands in Asymmetric Heck Reactions - Carbohydrates: Tools for Stereoselective Synthesis - page 241

O OH

O N

O

CO 2 Me

S1 S2 S3 S4 S5

cyclopentene 4,7-dihydro-1,3-dioxepine crotyl alcohol

2,3-dihydrofuran 2,3-dihydropyrrole

Figure 11.1 The most common substrates used for the intermolecular asymmetric Heck

reaction.

important parameter for high catalytic activity and enantioselectivity. A wide range
of bases has been employed in this process, with N , N -diisopropylamine and proton
sponge being the standard bases for testing new catalysts [1].
Notably, in the asymmetric intermolecular Heck reaction it is not only the
enantioselectivity of the process that needs to be controlled, the regioselectivity is
also a problem, because a mixture of regioisomers may be obtained. Consequently,
for example, in the Heck reaction of 2,3-dihydrofuran S1 with phenyl triflate a
mixture of two products is obtained, namely, 2-phenyl-2,3-dihydrofuran ( 1 ) and
the expected 2-phenyl-2,5-dihydrofuran ( 2, Scheme 11.2). The former is formed
due to an isomerization process [1].

[Pd chiral catalysts]

+ Ph-OTf

+

O Ph Ph

O O

S1 1 2

Scheme 11.2 Model Pd-catalyzed intermolecular Heck reaction.

Scheme 11.3 illustrates a proposed catalytic cycle for the phenylation of 2,3-
dihydrofuran [1, 2]. The catalytic cycle starts with the oxidative addition of the
organic triflate to Pd(0)-complex 3 to produce compound 4. Since the triflate ligand
in 4 is a good leaving group, coordination of 2,3-dihydrofuran on 4 induces dis-
sociation of the triflate ligand to give the cationic phenylpalladium olefin species
5, which has a 16-electron square-planar structure that is convenient for the sub-
sequent enantioselective insertion of the olefin. The resulting alkyl-palladium(II)
complex 6 undergoes -hydride elimination leading to a hydrido-palladium olefin

complex 7. Dissociation of this

β

-complex furnishes 2 and a hydrido-palladium
species 10. Finally, the catalytic Pd(0) complex 3 is regenerated by reductive elimi-
nation of HOTf. Depending on the ligand, catalyst precursor, and reaction param-
eters, the palladium complex 7 can also undergo re-insertion of the hydride, which
leads to the alkyl-palladium(II) complex 8.

π

β -Hydride elimination of 8 followed by

dissociation of the resulting -complex 9 leads to isomer 1 and hydride 10. Reduc-

tive elimination of HOTf in 10 regenerates active species 3.

π