Biomedical Engineering Reference
In-Depth Information
F
3
C
CF
3
CF
3
H
OTMS
CF
3
·HClO
4
88
(1.5 mol%)
Me
Me
CHO
+
+
H
2
O (7 equiv), 20°C, 6 h
61%
CHO
CHO
Me
87
69
89
(ee = 95%)
90
(ee = 78%)
70:30
H
Me
Me
[Cu(MeCN)
4
]BF
4
(5 mol%)
Me
Me
O
ClCH
2
CH
2
Cl
50°C, 140 min
OH
OH
-Santalol
(
93
)
92
97%
ee
after recrystallization
94%
91
β
SCHEME 6.17
Total synthesis of
b
-santalol via
exo
selective Diels-Alder reaction.
6.2.5. Pictet-Spengler Reaction
The Pictet-Spengler reaction has been widely used for the synthesis of natural
products such as alkaloids. It involves the intramolecular electrophilic cyclization of
an electron-rich aryl or heteroaryl group onto an imine or an iminium functional group
[33]. In this context, Jacobsen and Taylor reported the use of the chiral thiourea
catalyst
starting from 5-methoxy-
tryptamine (Scheme 6.18) [34]. List and coworkers showed that chiral Brønsted acid
catalysts such as
94
in their synthesis of carboline derivative
95
96
could be used to afford carboline derivatives such as
97
quantitatively with an excellent enantioselectivity [35].
Hiemstra and coworkers showed that an asymmetric Pictet-Spengler reaction
could be used to form piperidine-containing natural products such as arboricine
.
Isolated from the leaves of
Kopsia arborea
, arboricine showed a moderate ability to
reverse multidrug resistance in vincristine-resistant KB cells (Scheme 6.19) [36].
During the course of their synthesis, Hiemstra and coworkers demonstrated that chiral
Brønsted acid
103
100
catalyzed the Pictet-Spengler reaction between tryptamine
98
and
aldehyde
in good yield and with high enantioselec-
tivity (Scheme 6.19). Protecting group interconversion of the latter followed by a
palladium-mediated carbon-carbon bond formation and a final deprotection even-
tually led to arboricine
99
to afford the
b
-carboline
101
103
[37].
6.2.6. SOMO Reaction
The concept of singly occupied molecular orbital (SOMO) activation with a highly
selective
a
-allylation of aldehydes was first demonstrated by MacMillan and cow-
orkers and it involved the use of a chiral amine catalyst and a single-electron oxidant
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