Chemistry Reference
In-Depth Information
O
O
Me
Cl
Cl
R
Cl
10-20 mol % cat.*
N
Catalyst =
R
Nu
O
Nu
O
EtOAc, -40 to -60°C
t
-Bu
H
Cl
Cl
Cl
•TFA
Cl
67-97% yield
99->99% ee
N
Bn
Y
Nu =
R
2
N
R
3
OSi(R
4
)
3
X
X
R
1
Scheme 2A.25.
Enantioselective organocascade synthesis of α - chloroaldehydes.
20 mol % cat.*
R
2
CHO
R
1
O
Catalyst =
OTMS
Ph
En
Im
En
H
R
3
R
1
R
3
R
2
Ph
NO
2
NO
2
O
25-58% yield
7:3-10:1 dr
99->99% ee
Scheme 2A.26.
Enders ' triple organocascade sequence.
2A.4.2. New Activation Modes: O rgano SOMO Catalysis and
Photoredox Organocatalysis
To date, the concepts of iminium and enamine catalysis have provided more than 75
transformations for use in asymmetric synthesis [1]. However, a necessary objective for
the continued advancement of the fi eld of chemical synthesis is the design and imple-
mentation of new activation modes that enable previously unknown transformations. To
address this requirement, the enamine-activation platform was recently extended beyond
its original manifestation through the development of two innovative activation modes:
OrganoSOMO catalysis [39 - 41] and photoredox organocatalysis [42] .
2A.4.2.1. OrganoSOMO Catalysis
[39 - 41]
This new activation mode is founded on
the hypothesis that one-electron oxidation of an electron-rich enamine will selectively
generate a reactive 3π-electron radical cation. The electrophilic character of this SOMO
intermediate allows it to react with a variety of weakly nucleophilic carbon-based
SOMOphiles at the α-carbon of the parent enamine, providing formal alkylation prod-
ucts (Fig. 2A.3 ).
Applying the tenets of this design plan with a suitable one-electron oxidant has
proven highly successful and has already yielded a series of enantioselective transforma-
tions complimentary to those derived from enamine chemistry, including α - allylation
[39] , α - vinylation [40] , and α - enolation [41] of aldehydes (Scheme 2A.27 ).
2A.4.2.2. Photoredox Organocatalysis
[42]
The advent of SOMO activation demon-
strated that organocatalysis is not limited to conventional two-electron pathways for
enantioselective bond formations. Indeed, SOMO catalysis revealed not only that one-
