Chemistry Reference
In-Depth Information
TABLE 8C.2. ZACA Reaction of Substituted 1,4 - Pentadienes 20
Entry
R
1
R
2
R
3
R
(NMI)
2
ZrCl
2
Yield (%)
R
/
S
1
Me
H
H
Me
+
75
13/87
2
n
- Hex
H
H
Me
—
74
89/11
3
n
- Hex
H
H
Et
—
56
95/05
4
Ph
H
H
Me
—
75
90/10
5
Ph
H
H
Et
—
60
97/03
6
H
n
- Hex
H
Me
—
86
88/12
7
H
H
n
- Bu
Me
—
72
86/14
8
H
TBS
H
Me
—
72
85/15
9
H
TBS
H
Et
—
57
95/05
10
H
n
- Hex
Me
Me
—
79
89/11
11
H
Me
2
C = CH(CH
2
)
2
-
Me
Me
+
73
11/89
12
H
Me
Me
2
C = CH(CH
2
)
2
-
Me
+
68
10/90
13
H
n
- Hex
Cl
Me
—
73
90/10
14
H
n
- Hex
Cl
Et
—
69
96/04
15
Me
TBSO(CH
2
)
2
H
Me
—
75
92/08
16
Me
3
Si
H
Me
—
69
87/13
n
- Bu
17
H
Me
—
84
88/12
n
- Bu
n
- Bu
1) Me
3
Al
(NMI)
2
ZrCl
2
(5 mol %)
H
2
O, CH
2
Cl
2
,0°C
2) O
2
OH
R
R
O
OH
22
23
Scheme 8C.8.
the presence of water has been found critical as no product is formed in its absence. The
role of water is currently under investigation.
( − ) - Spongidepsin
24
, isolated from the Vanuatu marine sponge
Spongia
sp., has been
shown to exhibit cytotoxic and antiproliferative activities against J774.A1, HEK-293,
and WEHI-164 cancer cell lines [19]. Two key fragments
25
(C1 - C5) and
26
(C6 - C13),
comprising the C1-C13 portion of this macrolide, were synthesized en route to the total
synthesis of
24
in an effi cient manner using fully reagent-controlled ZACA reactions
[20]. The acid fragment
25
(dr ≥ 40:1 after chromatography of 5.5:1 dr product) was
prepared from allyl alcohol in seven steps, including two ZACA reactions to install two
methyl groups at the C2 and C4 positions. The alcohol fragment
26
(dr ≥ 40:1 after
chromatography of 3.5:1 dr product) was obtained from 1,5-pentanediol in seven steps,
including one ZACA reaction. It is noteworthy that unprotected ω - vinyl secondary
alcohols were successfully used in the ZACA reaction [20]. This fi nding has extended
the scope of the ZACA reaction. Subsequent esterifi cation, amidation, ring-closing
metathesis, and other functional group interconversions completed the total synthesis
of
24
(Scheme 8C.9 ) [20] .
