Chemistry Reference
In-Depth Information
were employed. Eventually, RedAl, [(CH
3
OCH
2
CH
2
O)
2
AlH
2
]Na, was employed as the
source of hydride under dilute conditions (
20
◦
C) to provide the desired bisallene-
bisalkyne in 70% yield. Presumably, the red Al first reacted with the hydroxyl groups
in
37
to give an intermediate in a rapid process. In a subsequent step, hydride was de-
livered intramolecularly to the sp carbon atom adjacent to the hydroxyl group through a
five-membered-ring transition state. This process furnished the desired allene
38
and was
presumably the rate-determining step. A similar regioselectivity was reported in the re-
ductive opening of an epoxy alcohol.
27
It is noteworthy that dilute conditions were found
to be optimal. At high concentrations of hydride, the nucleophile attacked the propargylic
carbon atom in an S
N
2 displacement of chloride and reduced the yield of allene
38
.Itis
also important to note that a different batch of Red Al would occasionally result in a lower
yield (
−
10
◦
C), then
the byproducts isolated were monoallene and the starting
37
, which could be recycled to
produce more of the desired bisallene
38
, if necessary. If one considers that two allenes
were formed in the same one-pot process, then this was considered a pivotal reaction in this
sequence. This was the first time, to these authors' knowledge, that Red Al was successfully
employed for this transformation.
28
A number of protecting groups were evaluated. The para-methoxybenzylidene acetal
39
could be formed more rapidly (4
∼
−
40%) of
38
. If the process was maintained at low temperature (
5h)byheating
38
with excess 4-methoxybenzaldehyde
dimethyl acetal under the above conditions in greater than 90% yield and was chosen for the
initial Pauson-Khand cyclization studies. Analogous to the conditions reported by Jeong
29
and Brummond et al.,
21
the bisallene
39
was heated in toluene to 100
◦
C in the presence of
a slight excess of Mo(CO)
6
(2.2 equiv) and 10 equivalents of DMSO. In approximately 5 h,
the starting
39
had been consumed and a new component of higher polarity was observed.
The new component was isolated in approximately 40% yield and eventually found to be
a mixture of diastereomers composed of the interesting [5.5.5.4] tetracycles
40a
and
40b
in a ratio of 5:4 (
40a
:
40b
). It was clear that the reaction conditions would have to be finely
tuned to provide the desired [5.5.5.5] tetracycles. Finally, on the basis of an understanding
of the reaction mechanism
19
modified reaction conditions were developed, which provided
the desired [5.5.5.5] tetracycle
41
(Scheme 8.7).
In this modification, a large excess of Mo(CO)
6
was heated in toluene to form a satu-
rated solution. The best temperature for this cycloaddition process had been narrowed to
53-55
◦
C. The saturated Mo(CO)
6
solution certainly provided a higher concentration of
the Mo
−
−
alkyne complex, to promote the tandem Pauson-Khand reaction at the expense of
the thermal [2
2] process. Again, the narrow temperature range (53 to 55
◦
C) was impor-
tant to obtain the [5.5.5.5] system in tetracycle
41
, and suppress the thermally mediated
[2
+
2] process. A lower temperature retarded the reaction rate, while higher temperatures
effected more of the undesired [2
+
+
2] four-membered ring formation in tetracycles
40a
and
40b
.
Attention turned to removal of the protecting group to regenerate the vicinal diol. It
was known that removal of the acetonide, para-methoxybenzylidene acetal or benzylidene
acetal from the corresponding tetracyclic systems under mild conditions would be difficult,
especially in the presence of the olefinic functionality. For this reason, the cyclic ortho ester
acetal
42
was chosen for further study, since it would be easier to remove. Indeed, after a
few attempts this protecting group was removed from dione
42
under mild conditions and
in very high yield. As shown in Scheme 8.8, the cyclic ortho ester
42
was heated in aqueous
