Page 18 - Volume 3, Issue 2, July 2010
Basic HTML Version
© Benaki Phytopathological Institute
Mihou & Michaelakis
48
graphically separablemixture of (5
R
,6
S
)- and
(5
S
,6
S
)-isomer. Oxidation of
69
followed by
deprotection, lactonization and acetylation
afforded the optically pure pheromone
1a
(
10 steps, 24.8% yield
).
Years later Sabitha
et al.
(2006) reported
the asymmetric total synthesis of (–)-(5
R
,6
S
)-
6-acetoxy-5-hexadecanolide via the key in-
termediate
75
which was prepared by a Gri-
gnard reaction from alcohol
71
as a major
product with anti-selectivity (80%
ee
). The
alcohol was easily accessed via two differ-
ent routes from THP protected hex-5-en-1-
ol
72
and epoxy chloride
73
(Figure 26) (
9
steps from 71, 14.5% yield
).
R
-2,3-Cyclohexylideneglyceraldehyde
has been used by Chattopadhyay to pre-
pare functionalized
δ
-lactones (Dhotare
et
al.
, 2005). Stereo-differentiating organo-
lithium addition to aldehyde
77
in hexane
and ether was found to be highly
anti
se-
lective leading to the required (
R
,
S
)-1,2-diol
unit. Subsequent functional and protective
group manipulations furnished (–)-(5
R
,6
S
)-
6-acetoxy-5-hexadecanolide (Figure 27) (
9
steps, 15% yield
).
A synthetic scheme starting from the re-
action between the lithiated
N
-allyl-
N
-meth-
yl-(bisdimethylamino)phosphoramide anion
and the triflate derivative of (
R
)-(–)-2,3-
O
-iso-
propylideneglycerolwasdescribedbyCoutrot
to prepare the key chiral synthon (
R
)-5-formyl-
δ
-valerolactone
83
(Figure 28) (Coutrot
et al.
,
1994). Chemo- and enantioselective addition
of
n
-decylmagnesium bromide to aldehyde
83
afforded (5
R
,6
S
)-6-hydroxy-5-hexadecan-
olide which after acetylation yielded the de-
sired pheromone
(7 steps, 13% yield)
.
2.5 Proline – catalyzed asymmetric al-
dol reactions
Years after his first publication on the
asymmetric synthesis of mosquito phero-
mone, Kotsuki reverted to the synthesis of
the target molecule with a convenient meth-
od for proline-catalyzed asymmetric aldol
reactions using synthons of straight-chain
aliphatic aldehydes and aldehydes bearing
a 1,3-dithiane moiety at the
β
-position (Ik-
ishima
et al.
, 2006). The required aldehyde
86
was readily prepared from ethyl acetoac-
etate after chain elongation. The aldol reac-
Figure 26
