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O
O
CH
3
O
CH
3
MeO
N
N
O
Rh(II)
O
O
N
2
OMe
H
H
N
N
Bz
Bz
42
43
O
O
H
CH
3
H
CH
3
H
MeO
N
HO
N
H
NH
NH
Lysergic acid
45
44
SCHEME 13.10
Given the success in forming novel azabicyclic systems derived from an
intramolecular isom
unchnone cycloaddition/
N
-acyliminium ion cyclization sequence,
this domino strategy was also used for a formal synthesis of vallesamidine
51
[21] via
the key Heathcock intermediate
50
(Scheme 13.11). Thus,
N
-malonylacylation of the
precursor amide was carried out followed by a standard diazo transfer reaction to
produce the requisite
€
-diazoimide
46
. The reaction of
46
with a Rh(II)-catalyst gave
cycloadduct
47
, which underwent a TMSOTf-catalyzed ring-opening to furnish
enamide
48
in 78% yield. With the ring-opened lactam in hand, a Barton-McCombie
deoxygenation reaction [22] delivered
49
in 88% yield. Utilization of the sequential
saponification/decarboxylation protocol afforded enamide
50
[23]. This sequence
a
NO
2
CO
2
Et
HO
CO
2
Et
O
O
Rh(II)
TMSOTf
Et
O
O
NO
2
N
N
NO
2
N
2
N
CO
2
Et
Et
Et
O
46
47
48
Barton
McCombie
H
CO
2
Et
H
O
O
O
Ref. [24]
KOH
N
N
N
NO
2
NO
2
N
Me
Et
Et
Et
(±)-Vallesamidine
51
50
49
SCHEME 13.11
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