Chemistry Reference
In-Depth Information
TIPS
Cl
OH
OH
TIPS
Red Al(3-4 eq.)
TIPS
O
ZnCl
Dry ether
+
TIPS
Dry
ether
TIPS
Cl
78 to
20 °C
−
−
Cl
O
OH
−
30 to
20 °C
yield
−
OH
36
70%
38
37
TIPS
35
PHOMe
TIPS
H
TIPS
MeOPh
H
MeOPh
H
O
,
10 eq DMSO, 100
°
C
2.2
eq
Mo(CO)
6
toluene
4-methoxybenzaldehyd
e
CH
O
TIPS
O
+
TIPS
PTSA,
refluxing
3
Cl
30-40%
O
91%
O
TIPS
O
TIPS
O
O
39
40b
(4)
40a
(5)
eq
10
6
20 eq DMSO, toluene
53-55 °C, argon, 48 h
65-70%
Mo(CO)
H
MeOPh
TIPS
O
O
O
TIPS
O
41
Scheme 8.7
Studies on the allenic tandem Pauson-Khand reaction.
The synthesis of the bisallene-bisalkyne
38
then took center stage. After a few attempts,
19
the desired (
)-diol
38
was obtained via the procedure illustrated in Scheme 8.7. The tetra-
alkyne
37
was synthesized by treatment of the 1,2-diketone
35
17e,22
with the alkynylide
of propargyl chloride. The propargyl chloride
36
was stirred with butyllithium in diethyl
ether at
±
78
◦
C to produce the alkynylide anion (the lithium anion survived only at
low temperature).
23
Zinc proved to be the best choice as the metal counterpart of the
alkynylide anion with respect to stereoselectivity and yield. A similar effect had been
observed previously by the authors in another system.
17
−
When lithium was employed
directly (M
Li) in this process, the yield was low and the undesired
meso
isomer
predominated. When magnesium was employed, this reaction provided the tetrayne
37
in
moderate yield with almost no stereoselectivity. Meso selectivity was also observed by
Diederich et al.,
24
=
when trimethylsilyl acetylenyl magnesium was reacted with the same
1,2-diketone
35
.
However, when zinc was employed as the metal counterpart to stabilize the carbanion
(produced by treating the lithium alkynylide of propargyl chloride with anhydrous ZnCl
2
at low temperature), the yield increased to over 80% and the desired dl diastereomer of
37
predominated in a ratio of 6:1 over the
meso
isomer. To date, the Felkin
Anh model
25
of
addition can be employed to rationalize the observed stereoselectivity of the zinc-mediated
process.
Lithium aluminum hydride has been reported in the literature
26
as the reagent of choice
to convert propargyl chlorides into allenes. Unfortunately, when the tetrayne
37
was treated
under the reported conditions,
26
a complex mixture of products was obtained with the de-
sired bisallene-bisalkyne
38
present in very low yield. A number of other hydride sources
−