vinylation as the final step (Scheme 42) [132]. The required vinyl iodide was used
as a mixture of isomers (E:Z ¼ 9:1). Unfortunately, an isomerization of the double
bond occurred in the course of the coupling to yield the target product as a 2.5:1
mixture of E:Z-isomers, which could then be separated by HPLC.
Likewise, Nicolaou observed such isomerization when attempting a coppermediated vinylation under modified Porco’s conditions in the total synthesis of
the polyketide apicularen A [133, 134]. Thus, when starting from a vinyl iodide
consisting of a 9:1 mixture of E:Z isomers the target enamide was obtained as a 10:1
mixture (E:Z). The final product was then obtained after chromatographic separation. Alternatively, Panek described the total synthesis of the same natural product
using a copper-promoted vinylation at the late stage of synthesis (Scheme 43)
[135]. Isomerization of the double bond accompanied the target enamide formation
and a mixture of iodides (E:Z ¼ 6:1) furnished the desired apicularen A as an 8:1
E:Z mixture. Remarkably, the addition of 1,10-phenanthroline and reaction temperature proved essential parameters for the reaction outcome.
O
O
OH
OH
I
Me
Rb 2 CO 3 , DMA, 90 ºC
57%
CuTC (50 mol%)
H 2 N
Et
O
O
O
OH
OH
Me
HN
Et
O
salicylihalamide A: 17 (E )
salicylihalamide B: 17 (Z )
Scheme 42 Synthesis of alkaloids salicylihalamide A and B
O
O
OH
O
H
H
I
HO
O
O
OH
O
H
H
H
N
HO
O
Et
Rb 2 CO 3 , DMA,
58 ºC
40%
CuTC (2.2 equiv),
L9 (4.5 equiv)
H 2 N
Et
O
apicularen A
Scheme 43 Synthesis of polyketide apicularen A
O
O
O
K 2 CO 3 , DMA, 50 ºC
CuTC (1.7 equiv),
DMEDA (3.4 equiv),
oximidine II
I
OMOM
TBS
O
O
OH
HN
OH
O
N
MeO
N
H 2 N
O
OMe
1)
2) HF-pyridine
(44%, 2 steps)
Scheme 44 Synthesis of oximidine II
Metal-Catalyzed C(sp
2
)–N Bond Formation
79