Chemistry Reference
In-Depth Information
O
Me
PG
OTBS
20 mol % cat.*
N
PG
OTBS
N
Catalyst =
H
R
O
t
-Bu
CHCl
3
, -20°C
R
H
O
Ph
•
p
-TSA
69-92% yield
87-97% ee
Scheme 2A.6.
Enantioselective conjugate addition of amines using iminium catalysis.
Jørgensen and others utilized a similar approach for the enantioselective β -
hydroxylation of aldehydes (Scheme 2A.7) [16]. In conjunction with enamine-controlled
α - hydroxylation (
vide infra
), this provides convenient access to enantioenriched α - and
β - hydroxyaldehydes.
F
3
C
Ph
N
10 mol % cat.*
O
N
Ph
Catalyst =
CF
3
R
O
HO
PhMe, 4°C
R
O
H
OTMS
60-75% yield
88-97% ee
F
3
C
CF
3
•PhCO
2
H
Scheme 2A.7.
Enantioselective
β
- hydroxylation using iminium catalysis.
2A.2.3. Transfer Hydrogenation
The hydrogen atom is the most common discrete substituent found among stereogenic
centers. It is, therefore, unsurprising that the fi eld of asymmetric catalysis has focused
great attention on the invention and development of enantioselective hydrogenation
protocols. While these powerful methods rely mainly on the use of organometallic cata-
lysts and molecular hydrogen, it is important to consider that the large majority of
hydrogen-containing stereocenters are created in biological cascade sequences involving
enzymes and organic cofactors. Based on this, a unique metal-free, biomimetic hydro-
genation method was developed employing the LUMO-lowering iminium concept as the
activating mechanism. Indeed, the selective reduction of
β
,
β
- disubstituted
α
,
β
-
unsaturated aldehydes and
-unsaturated ketones could be accomplished
under iminium control, employing Hantsch esters as the hydride donors, with high levels
of enantiocontrol (Scheme 2A.8 ) [17,18] .
A noteworthy feature of this transformation is that the sense of asymmetric
induction is not related to the geometry of the olefi n starting material. As a consequence,
mixtures of
E
/
Z
- olefi n isomers can be employed to provide enantiomerically pure hydro-
genation adducts, a desirable, yet rare, feature for catalytic hydrogenations (Scheme
2A.9 ) [17] .
β
- substituted
α
,
β
