Regioselective ring opening of α-substituted α-alkynyl oxiranes to 2-substituted 3-butyn-1-ols

Article abstract of DOI:10.1016/S0040-4039(00)60808-0

Treatment of α-substituted α-acetylenic epoxides with DIBAH in THF provides 2-substituted 3-butyn-1-ols in high yield avoiding propargyl/allene isomerization.

Full text of DOI:10.1016/S0040-4039(00)60808-0

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Regioselective Ring Opening of a-Substituted
to
Peter
Anton
Department of Dermatology, SANDOZ Forschungsinstitut
59, A-1235 Vienna
Treatment of a-substituted a-acetylenic epoxides with DIBAH in THF provides
in high yield avoiding propargyllallene isomerixation.
Addition of titanium acetylides to monosubstituted oxiranes is the only synthesis of
3 reported so
reduction of a-substituted a-alkynyl epoxides could give ready access to homopropargylic alcohols 3.
Reductive ring opening of 1 can, in principle, yield the regioisomeric alcohols 2, 3 and 4.
addition to the possibilities arising from regioselectivity and
that generates high yields and is generally applicable. We envisaged that
isomerixation, the non
and 7 has to be considered depending on the of the reducing
reductive formation of products
agent, which might act as
or
and the
For the reductive ring opening of
a-vinylic and a-allenic oxiranes it has been reported that the regioselectivity can be influenced by varying
the reducing agent and the
l
Testing several combinations of reducing agents
n-butyl) the following results were
with different
As expected
solvents in the reduction of oxirane la
=
reduction of la with
in ether exclusively generated propargylic alcohol
product
resulted in a mixture of
15%). Finally, when DIBAH in THF was used, la was almost quantitatively
whereas the use of
70%) and its allene
in ether produced mainly the desired
isomer 4a 20%).
4a 45%) and
of la with DIBAH in
converted to
96%). In addition to the high regioselectivity observed in this reaction, the extremely low
amount of allene isomer 4a produced
1%) is particularly noteworthy.
7507

7508
The results of the treatment of epoxides la-d7 with 1.2 equivalents of
for one hour at
C
in THF, followed by workup with aqueous ammonium chloride solution, are
in the following
scheme (yields were determined by GC-analysis):
(87%)
(80%)
Following this
alcohols
epoxides la and lb were converted nearly quantitatively into
respectively. The ring opening with
and 2b were not detectable in the crude product mixture by
only
obtained by reduction of oxirane lc with
of isomeric alcohol and, differing from the other reactions, about
were also formed. Treatment of the product in good
(7%). probably due to increased steric
and
alcohols
comparative GC-analysis) and with extremely low isomerixation to allenic products (4a and 4b
detectable by GC in about 1 and 0.6 percentage). The yield of
was high. However,
10% of allenic aldehyde
yield, but gave also minor amounts of alcohols 4d (9%) and
hindrance in compound
The usefulness of the method in preparative chemistry was demonstrated by the synthesis of
analytically pure and on a gram scale with yields of 86% and 77%. Therefore, the described method is
a good alternative to the ring opening of oxiranes with titanium acetylides.
addition, it offers the
a-acetylenic
possibility of synthesizing
starting from
epoxides.
1.
2.
Krause, N.;
A. Small Ring Heterocycles, Part 3.
Weissberger, A,; Taylor, EC. John
D. Chem. Ber.
The Chemistry of Heterocyclic Compounds;
and Sons, Jnc: New York, 1985; Vol. 42. pp. 62-71.
Org. Khim.
3.
4.
5.
6.
7.
Perveev, F.Ya; Gonoboblev, L.N.
Perveev. F.Ya Chem.
R.S.; Katxenellenbogen, J.A. Am.
3.; M. Bull. Chim. France
la-d were synthesized by reacting the respective lithium acetylides with the appropriate
957-959.
(Received in Germany
3 August 1992)