Chemistry Reference
In-Depth Information
Siphonarienolone
28
is a polypropionate produced by the mollusks of the genus
Siphonaria
[21] . Effi cient synthetic routes to
28
and two other structurally related
siphonarienes
29
and
30
, bearing three chiral centers (1,3,5-
syn - syn
) were devised using
a series of ZACA reactions [13]. Key intermediate
27
was obtained in seven steps (three
ZACA reactions) from 3 - buten - 1 - ol with excellent enantio - and diastereoselectivity
(Scheme 8C.10). Conversion of
27
to siphonarienolone
28
as well as siphonarienal
29
and siphonarienone
30
required only two to six additional steps (Scheme 8C.11).
1) (+)-(NMI)
2
ZrCl
2
(5 mol %)
n
-Pr
3
Al, IBAO
1) Swern oxidation
2) CH
2
=PPh
3
OH
2) H
3
O
+
OH
90% ee
1) (+)-(NMI)
2
ZrCl
2
(5 mol %)
Me
3
Al, MAO
2) O
2
1) Iodination
2) CH
2
=CHBr, [Pd]
3) (+)-(NMI)
2
ZrCl
2
(5 mol %)
Me
3
Al, MAO
4) O
2
OH
OH
27
dr
40/1
50%overfoursteps
from 3-buten-1-ol
≥
dr
50/1
46 % for three steps
≥
Scheme 8C.10.
2steps
OH
CHO
27
Siphonarienal (
29
)
7 steps from 3-buten-1-ol
23% overall yield
4 steps
4steps
OH
O
O
Siphonarienone (
30
)
Siphonarienolone (
28
)
Scheme 8C.11.
One - pot tandem ZACA - Pd - catalyzed cross - coupling process has been successfully
applied to the synthesis of
- diheterofunctional reduced polypropioates, starting
from styrene (Scheme 8C.12) [22]. The ZACA methylation of styrene catalyzed
by (
α
,
ω
) - ZACA, ” generated the corresponding 2 - phenyl - 1 - Me
2
Al -
propane, which was subjected to the Pd-catalyzed cross-coupling reaction with bromo-
ethene in one pot to give 4 - phenyl - 1 - pentene
31
with 89% ee. The second ZACA
methylation of
31
catalyzed by (+)-(NMI)
2
ZrCl
2
, “ (+) - ZACA, ” followed by oxidation
afforded (2
S
,4
S
) - 4 - phenyl - 1 - pentanol
32
with 7:1 dr and 92% enantioselectivity in 50%
−
) - (NMI)
2
ZrCl
2
, “ (
−
