Chemistry Reference
In-Depth Information
NH
2
35 mol % cat.*
O
O
O
N
HPMP
Catalyst =
CO
2
H
N
H
H
R
Acetone or CHCl
3
or DMSO, RT
R
OMe
35-90% yield
70-96% ee
Scheme 2A.14.
Enamine - catalyzed three - component Mannich reaction.
NH
2
NH
PMP
i) 30 mol % cat.*, DMF, -20°C
O
O
Catalyst =
CO
2
H
HO
Ar
H
R
H
Ar
ii) NaBH
4
H
R
OMe
77-92% yield
4:1-138:1 dr
84->99% ee
Scheme 2A.15.
Enamine - catalyzed aldehyde - aldehyde Mannich reaction.
2A.3.2. Carbonyl α - Halogenation, α - Nitrogenation, α - Oxygenation,
and
- Sulfenylation
The direct and enantioselective
α
-functionaliztion of carbonyls remains a broadly valued
transformation, given the inherent value of the corresponding products. In this context,
the extraordinary success of enamine activation has led to its implementation within a
host of carbonyl
α
-functionalization strategies. In particular, the organocatalytic instal-
lation of heteroatoms is an area that has been explored with some tenacity.
α
2A.3.2.1. Carbonyl
-halogenation of aldehydes has been
accomplished under enamine control using F-, Cl-, Br- and I-based electrophiles. Mac-
Millan and coworkers found that
α
-Halogenation
The
α
- chlorination processes take place
using the same imidazolidinone organocatalyst to provide
α
- fl uorination and
α
- halocarbonyl derivatives
with excellent enantioselection (Scheme 2A.16, eq 1 and eq 2) [26]. Similarly, Jørgensen
and others found a
C
2
-symmetric pyrrolidine catalyst to be effective for
α
α
- bromination
and
α
- iodination, although the
α
-iodination reactions are generally less selective (Scheme
2A.16 , eq 3 and eq 4) [27] .
-Amination
The ubiquitous nature of nitrogen within many bio-
logically active compounds has rendered the installation of nitrogen functionality a
major area of interest. The direct enantioselective formation of C-N bonds has therefore
become an attractive pursuit for many practitioners of enamine catalysis. Using a suit-
able nitrogen electrophile, the direct
2A.3.2.2. Carbonyl
α
-amination of carbonyl compounds may be carried
out under enamine catalysis. In this regard, azodicarboxylates have been found to be
ideal sources of N
+
. In the presence of catalytic proline,
α
- aminoaldehyde derivatives
are expediently prepared with high levels of enantiopurity (Scheme 2A.17) [28].
More recently, Maruoka and coworkers showed that careful consideration of the
catalyst structure allows the use of nitrosobenzene as the electrophilic nitrogen source,
providing an exceptionally selective procedure (Scheme 2A.18 ) [29] .
α
