Chemistry Reference
In-Depth Information
DEAD, PPh
3
CO
2
Me
+
HO
CO
2
Me
11.244
NHTs
N
Ts
11.243
11.245
Grubbs II
H
2
C=CHOSiMe
3
(Ph
3
P)
3
(OC)RuHC
l
CO
2
Me
N
Ts
11.246
O
CO
2
Me
n
-C
18
H
37
H
N
Ts
11.247
11.248
Scheme 11.82
An intermolecular diene cycloisomerization was the key step in a synthesis of the putative structure of
fistulosin
11.248
, an anti-fungal compound from Welsh onion roots (Scheme 11.82).
113
The substrate
11.246
could be prepared by Mitsunobu alkylation of a sulfonamide
11.243
, followed by migration of the double
bond with a ruthenium catalyst. The cycloisomerization was achieved using a species generated from the
Grubbs second-generation catalyst and the silyl enol ether of acetaldehyde. When the target structure
11.248
was finally reached, the spectroscopic data showed that the reported structure of the natural product was
incorrect.
The alkene component of the ene-yne cycloisomerization can be replaced with a carbonyl group
(Scheme 11.83). Treatment of the alkynyl ketone
11.249
with a low-valent nickel catalyst gave a nickel-
lacycle
11.250
. When an organozinc reagent was used in the presence of the nickel catalyst, the reaction is
not strictly a cycloisomerization, as additional atoms are transferred. With dimethyl zinc, a methyl group is
transferred, with diethyl zinc, a hydrogen atom is transferred as
-hydride elimination is rapid (compare to
Scheme 4.92).
114
Silyl hydrides, however, prove to be a more convenient source of the hydrogen atom, and
directly deliver protected alcohols.
115
This reaction has been used with a highly functionalized alkyne
11.253
in a synthesis of allopumiliotoxin 339A
11.255
(Scheme 11.84).
116
Me
HO
R
Me
2
Zn
Ni
Ni(COD)
2
,
n
-Bu
3
P
R
O
R
O
11.251
H
H
Et
2
Zn
HO
R
11.249
11.250
11.252
Scheme 11.83
