Chemistry Reference
In-Depth Information
(
S
,
R
,
R
,
S
,
R
,
S
) - 4,6,8,10,16,18 - hexamethyldocosane
15
, isolated from the cuticula of
cane beetle
Antitrogus parvulus
[7] was found to possess rarely seen
anti
-
anti
-
anti
-
4,6,8,10-methyl tetrad along with the usual
syn
- methyl diad [8] . The ZACA reaction has
been applied to the synthesis of
15
[9]. The ZACA reaction was used to generate fi ve
of the six asymmetric carbon centers with the sixth being derived from (
S
) -
β
- citronellal.
The key intermediate, aldehyde
13
, was prepared from (
S
) -
- citronellal in nine steps
including three ZACA reactions in 13% overall yield (Scheme 8C.4). Hexamethyldoco-
sane
15
was obtained through coupling of aldehyde
13
having four of the requisite six
chiral centers with phosphorane
14
(obtained from propene in six steps including two
ZACA reactions in 23% overall yield) via Wittig olefi nation followed by hydrogenation
in 85% yield for two steps (11% overall yield from (
S
) -
β
β
- citronellal) (Scheme 8C.5 ) [9] .
1) (NMI)
2
ZrCl
2
(4 mol %)
Me
3
Al, CH
2
Cl
2
2) O
2
CH
2
=PPh
3
O
8
(
S
)-
β
-citronellal
1) (NMI)
2
ZrCl
2
(3 mol %)
Me
3
Al, CH
2
Cl
2
2) Zn(OTf)
2
, DMF, 70°C
3) Pd(DPEphos)Cl
2
(3 mol %)
DIBAL-H, CH
2
=CHBr
1) I
2
,PPh
3
2) ZnBr
2
,CH
2
=CHBr
Pd(PPh
3
)
4
(2 mol %)
HO
9
10
60%, dr
≥
95/5
1) (NM I)
2
ZrCl
2
(4 mol %)
Me
3
Al, CH
2
Cl
2
2) O
2
HO
11
12
45%, dr
≥
98/2
1) TsCl, Et
3
N
2) EtMgBr, 5% Li
2
CuCl
4
3) NMO, OsO
4
(1 mol %)
NaIO
4
CHO
13
(9 steps from (
S
)-
β
-citronellal,
13% overall yield)
Scheme 8C.4.
1) n-BuLi, THF
+
IPh
3
P
CHO
2) H
2
,Pd
14
(6 steps from propene,
23% overall yield)
13
(9 steps from (
S
)-
-citronellal,
13% overall yield)
β
(
S
,
R
,
R
,
S
,
R
,
S
)-4,6,8,10,16,18-hexamethyldocosane
15
(11 linear steps from (
S
)-
β
-citronellal, 11% overall yield)
Scheme 8C.5.
