Chemistry Reference
In-Depth Information
Organocatalytic Friedel-Crafts alkylations of substituted pyrroles
O
Me
20 mol % cat.*
R
1
R
1
N
Catalyst =
Me
Me
O
(eq 1)
R
O
N
R
2
N
H
THF, H
2
O, -30 to -60°C
R
R
2
Ph
•HX
68-90% yield
87-97% ee
HX = TFA, TCA or NCCH
2
CO
2
H
Organocatalytic Friedel-Crafts alkylations of substituted indoles
R
O
Me
20 mol % cat.*
N
R
1
O
Catalyst =
(eq 2)
R
O
R
1
N
R
2
CH
2
Cl
2
,
i
-PrOH
-50 to -87°C
H
t
-Bu
N
R
2
Ph
•TFA
70-94% yield
89-97% ee
Organocatalytic conjugate addition of substituted anilines
R
O
Me
R
2
20 mol % cat.*
R
2
N
Catalyst =
(eq 3)
R
O
O
CH
2
Cl
2
or CHCl
3
-50 to 20°C
t
-Bu
N
H
(R
1
)
2
HN
(R
1
)
2
HN
Ph
•HCl
65-97% yield
84-99% ee
Organocatalytic Mukaiyama-Michael reaction
O
O
Me
20 mol % cat.*
O
N
Catalyst =
R
1
(eq 4)
R
O
R
1
O
TMSO
O
t
-Bu
CH
2
Cl
2
, H
2
O
-20 to -70°C
H
Ph
R
•DNBA
73-87% yield
1:6-31:1
syn
:
anti
84-99% ee
Organocatalytic Friedel-Crafts alkylaions with trifluoroborate salts
Ar
Ar
O
BF
3
K
O
Me
20 mol % cat.*
R
N
Catalyst =
o
o
r
R
O
(eq 5)
t
-Bu
H
HF, DME, -20°C
•HCl
BF
3
K
O
X
N
X
R
Bn
69-97% yield
87-97% ee
Scheme 2A.5.
Iminium - catalyzed alkylation of electron - rich aromatic/vinyl substrates.
More recently, several groups have reported expansions of the iminium catalysis
paradigm to demonstrate the enantioselective conjugate addition of carbogenic nucleo-
philes such as nitroalkanes, malonates, 1,3-dicarbonyl compounds, and β - ketosulphones
to a number of acyclic α , β-unsaturated ketones [1,2]. One particularly interesting use of
iminium activation has been the enantioselective conjugate addition of amines to α , β -
unsaturated aldehydes. In this case, rational consideration of the stereoelectronic nature
of both organocatalyst and nucleophile resulted in the development of a convenient
method for the preparation of C-N stereogenic compounds with high enantioselectivity
(Scheme 2A.6 ) [15] .
