Chemistry Reference
In-Depth Information
6.4 Chiral Promoters
6.4.1 Sulfoxides
Sulfoxides can be used as PK promoters. For example, Jeong and Pauson attempted
to use the chiral sulfoxide
7
to promote intramolecular PKR of enyne
6a
, which re-
sulted in no induction.
12
The hemilabile coordinating behavior of sulfoxides on di-
cobalt clusters has recently been documented and anticipates the failure of this approach
(Scheme 6.7).
O
S
Me
(OC)
3
Co
Co(CO)
3
Me
7
EtO
2
C
EtO
2
C
EtO
2
C
Co
2
(CO)
8
O
H
EtO
2
C
C
6
H
6
, 40 °
C
EtO
2
C
EtO
2
C
H
6a
8
90% yield
0% ee
Scheme 6.7
Non enantioselective PKR promoted by a chiral sulfoxide.
6.4.2 Chiral
N
-Oxides
Tertiary amine
N
-oxides are the most effective promoters reported to date for stoichiometric
PKRs. These reactions can be run at temperatures as low as
70
◦
C, depending on the
substrate. In 1998, Kerr reported the first ever use of a chiral
N
-oxide (brucine
N
-oxide [
4a
])
as a promoter in the asymmetric PKR.
13
The Laschat group later extended this approach
to a series of structurally diverse alkaloid
N
-oxides.
14
However, they did not achieve better
enantioselectivity: their best result, obtained with brucine
N
-oxide, was 78% enantiomeric
excess (Scheme 6.8).
Moreover, this methodology seems to be restricted to propargylic substrates. Researchers
have postulated that the preferential attack to the CO ligand at one of the enantiotopic cobalt
vertices by the
N
-oxide is facilitated by tethering of the reagent to the cobalt complex
through hydrogen bonding between the
N
-oxide and the hydroxyl group of the latter. The
reaction must be run at low temperature to prevent isomerization (through COmigration) of
the highly unstable (chiral) unsaturated complex that results from CO loss. Olefin insertion
onto the opposite cobalt atom would lead to inversion in the absolute configuration of the
product (Scheme 6.9).
Whether the resulting chiral tertiary amine byproduct contributes to the asymmetric
induction has been the subject of debate. However, recent attempts to use chiral primary
amines to promote asymmetric PKRs have failed. For example, cyclization of the cobalt
complex
10
promoted by the chiral amines
11a-c
afforded the tricyclic enone
12
in racemic
form (Scheme 6.10).
15
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