Chemistry Reference
In-Depth Information
cyclopentobarbital and pentobarbital were provided. The high selectivity does not mean
that the fundamental problem was solved, because the ratio of epimeric products with
respect to the starred center was only on the order 2:1. Thus, there remains a challenge
for the development of chiral ligands with a small confi ned cleft for the incorporation
of the nucleophile.
8B.2.2.5. Preparation of Allenes via Allylic Alkylation
The Pd - catalyzed enanti-
oselective allylic alkylation allows the preparation of chiral allenes, which are of
interest in natural product synthesis. Two general approaches have been developed,
which differ in the starting material from which an
exo
- (alkylidene -
- allyl)Pd species
is formed (Scheme 8B.34). This intermediate reacts with a soft nucleophile at the
sterically less hindered allylic terminus and from the direction opposite to palladium.
In principle, enantioselectivity can arise either in the oxidative addition step, if one
of the diastereoisomeric
exo
- alkylidene - (
π
-allyl)Pd intermediates is formed preferen-
tially, or/and because of differing reactivities of the equilibrating diastereoisomers in
the attack of the nucleophile. The latter constitutes again a dynamic kinetic resolu-
tion process, and a suffi ciently fast equilibration between the Pd complexes is essential
for success.
π
X
H
R
•
H
Br
R
R
R
R
[Pd]
[Pd]
[Pd]
Nu
H
Nu
•
H
R
Scheme 8B.34.
Preparation of allenes via Pd-catalyzed allylic substitution.
8B.2.2.5.1. 1 - Substituted 2 - Bromo - 1,3 - Dienes as Substrates
In the fi rst attempt toward
axially chiral allenes, Hayashi et al. [143] used 1 - substituted - 2 - bromo - 1,3 - butadienes
as substrates and
BINAP
as ligand (Table 8B.17). In this approach, an
exo
- (alkylidene -
π
-allyl)Pd intermediate is formed by oxidative addition of the Pd
0
- complex to the
alkenyl bromide and subsequent
-isomerization. Attack of the nucleophile occurred
at the less hindered terminus and gave products with up to 89% ee. Hayashi et al.
discovered that free dba enhanced the enantioselectivity of the reaction due to its
ability to accelerate the equilibration between the diastereomeric
exo
- (alkylidene -
σ
-
π
π
-
allyl)Pd intermediates. They were able to isolate an (alkylidene-
- allyl)Pd complex, a
mixture of diastereomers in solution, and study stoichiometric substitution reactions.
Good results were also obtained with
TMS - BINAP
[135] and
SEGPHOS
[144] as
ligands.
π
