Vol.
2703
to 2709,
Tetrahedron
40, No .
$3.00
+
1984
Lt d .
Prin t ed in t h e U.S.A.
SYNTHESIS OF
BY THE
INTRAMOLECULAR RING TRANSFORMATION OF
E
IKOH
and Kon
Institute of Applied Organic Chemistry, Faculty of Engineering, Nagoya University, Furo-cho,
Nagoya 464, Japan
(Received in Japan 5 August 1983)
were synthesized by intramolecular ring transformation starting
from y-keto-1,3,4-oxadiaxoles 5 and 9. The required functionality for this intramolecular reaction was
established by (i) the reaction of lithiated
4 with the methyl enol ether of
of y-ketones and 9 to further
and (iii) pyrolysis of 7 and
treatment, the S-connected
a-bromo ketones followed by hydrolysis; (ii) reductive
reorganized hydraxide 7 and
9 with
8 and 1 1 . By the
9 at 280” (5
to the
2 afforded the desired fused s-triazole 17.
aged via the coupling reaction of metalated
2-methyloxadiazole 4 with masked a-halo ketones i.e.
An intramolecular version of either intermolecular
substitution or addition reaction has received much
attention and provided quite a capable strategy for
the synthesis of polycondenced molecules, often with
high regio- and stereo-selectivities. Particularly high-
2-methoxyallyl bromide
oxycyclohexene
and
For this purpose,
diazole
was lithiated with
at -78”
lighted is the application of the
reaction.
according to the procedure reported by Meyers’ and
then treated with 12. However, to our disap-
pointment, this reaction did not give the desired
On the other hand, an intramolecular ring trans-
formation has been sparsely applied except for the
transformation of a
ring to a pyrrole ring,’
y-ketone
but instead an intractable mixture of
although it could potentially provide an attractive
route to a variety of bridgehead nitrogen
cycles. From this viewpoint, we have previously
demonstrated the synthesis of
from
products after acidic work-up. The use of HMPA as
a co-solvent could solve the problem; the above
reaction carried out with
in
(v/v)] gave 38% yield of
after purification by
chromatography and subsequent recrystallization.
Likewise, cyclohexanonylation of
zoles as exemplified in Scheme
sulfur was used as a conjunctive atom between an
oxadiazole ring and a chain, and the intra-
in the
step (a)
was su ccess-
fully achieved on treatment of the lithiated 4a with 13
in the same mixed solvents. The other y-ketones with
a p-substituent were obtained in a similar manner.
The yields and physical properties of 5a-d and 9a-d
are summarized in Tables 1 and 2. The acetonylation
was also at-
molecular replacement of the oxygen in the
adiazole ring with the nitrogen was the key ring
closure step
The method thus established can be extended to
the synthesis of other fused s-triazoles. In the course of
of our program, a similar type of the reaction of
tempted under the same conditions as before but the
in which the bridging atoms corresponding y-ketone was not obtained. Although
are all carbons was further investigated. This paper no effort was made to identify the products, we
deals with the preparation of y-ketones and their presume that ring cleavage of the lithiated oxadiazole
transformation to pharmacologically interesting’ occurred as suggested by Micetich.”
and
Transformation of
s-triazoles
to fused
by the
cyclodehydration of the corresponding
First the transformation of the obtained y-ketones
based on our intramolecular ring transformation
to cyclopentano[c]-s-triazoles such as
pyrrolo-s-triazoles
8
and
hexahydro-9H
RESULTS AND DISCUSSION
triazoloindoles 11 was investigated. The requisite
Preparation of
5a-d a n d y-amino function was easily envisioned by a func-
tional conversion of a y-ketone. Accordingly, 5a-d
The preparation of
was
were reductively aminated with
in the
Scheme 1
2703