Chemistry Reference
In-Depth Information
Proximal Distal
Nu
Proximal:
CH
3
, OR
′
R
R
Distal:
alkyl
≠
CH
3
, aryl, SR
′
,
CH
2
OR
′
, CF
3
, SiMe
3
R
[Pd]
[Pd]
Figure 8B.1.
Regioselectivity of Pd - catalyzed allylic alkylations.
(1) Steric effects favor the sterically better accessible carbon atom of the allyl unit.
This effect can be overruled by electronic effects. This is most apparent from the
fact that 1-methyl- and 1,1-dimethylallyl derivatives display a preference for
reaction at the methylated, proximal terminus, while general 1-alkylallyl deriva-
tives show preference for reaction at the distal terminus.
(2) Conjugating substituents (e.g., Ph, COOR, CN) favor the distal position, as
would be expected for a late transition state refl ecting the stability of the product
olefi n complex.
(3)
σ
- Electron - withdrawing
substituents
(CH
2
OR, CF
3
[19]) favor the distal
terminus.
(4) If all other factors are equivalent, the carbon center better stabilizing a positive
charge seems to be preferred. Thus, OR
[21] and
SiMe
3
[22] the distal center. There is only one example of a system, which is
solely controlled by electronic effects of the substituents [23]. Note that a phenyl
group directs to the distal position, despite its charge stabilizing effect, on an
allyl cation not coordinated to Pd.
(5) The electronic properties of the ligands are important in that relative positive
charges at the allylic termini are enhanced in proportion to the acceptor strength
of the ligands. There are examples of changeover of regioselectivity with ligands
[24] .
(6) Substituents in the allylic substrate or the ligand interacting with the nucleophile,
for example, by hydrogen bonding or via the counter cation (cf. Section 8B.2.2.3),
or Pd
II
[25], can control the position of attack of the nucleophile.
(7) Reactions proceeding via
syn
,
anti
- (
′
[20] favors the proximal, SR
′
-allylic) complexes show a preference for
the reaction at the
anti
-terminus, giving rise to
trans
- rather than
cis
- products,
as would be expected for a late, product-like, transition state [26,27].
(8) If two different ligand donor centers are present, for example, P and N, substitu-
tion
trans
to the center possessing the higher
trans
infl uence is preferred.
(9) Finally, the infl uence of the nucleophile can be dominant. A rare example are
hydrazines, which add kinetically controlled at the substituted terminus of mono-
substituted (allyl)Pd complexes [28] .
π
Note that these rules refer to kinetically controlled reactions. Thermodynamic control
has been observed several times and follows other rules, because the organic product is
the one that has to be considered, while in kinetically controlled reactions, the (olefi n)
Pd complex is the product that counts.
