SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900853
One-Pot Assembly of 7-Methylene-6,8-dioxabicyclo[3.2.1]octanes, Congeners
of Frontalin, from Ketones and Acetylene
Boris A. Trofimov,*[a] Elena Yu. Schmidt,[a] Igor A. Ushakov,[a] Albina I. Mikhaleva,[a]
Nadezhda V. Zorina,[a] Nadezhda I. Protsuk,[a] Elena Yu. Senotrusova,[a]
Elena V. Skital’tseva,[a] Olga N. Kazheva,[b] Grigorii G. Alexandrov,[c] and
Oleg A. Dyachenko[b]
Keywords: Ketones / Alkynes / Oxygen heterocycles / Pheromones / Superbasic systems
A facile, consecutive, self-consisting assembly of two mole-
cules of ketones with two molecules of acetylene to afford 7-
methylene-6,8-dioxabicyclo[3.2.1]octanes, which are un-
known congeners of widespread insect pheromones, has
been discovered. The reaction is realized in a one-pot pro-
cedure in a MOH/DMSO system (M = K, Cs) at 80 °C for 1 h
under acetylene pressure or under atmospheric pressure; the
isolated yields of the bicycles reached 86%. The new reac-
tion conceptually contributes to the synthesis of insect phero-
mones as well as to the chemistry of ketones and acetylene.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Results and Discussion
It is well known that ketones react with acetylene in the
presence of bases to furnish acetylenic alcohols (Favorsky
reaction).[1] To our surprise, when conducting the reaction
of aromatic and heteroaromatic ketones 1a–e with acetylene
in MOH/DMSO (M = K, Cs) at 80 °C for 1 h under acetyl-
ene pressure (autoclave, initial acetylene pressure at ambient
temperature 12–14 atm), we isolated, instead of the ex-
pected acetylenic alcohols 2a–e, 7-methylene-6,8-dioxabicy-
clo[3.2.1]octanes 3a–e as the only products in up to 86%
yield (Scheme 1, Table 1).
The 6,8-dioxabicyclo[3.2.1]octane[2] scaffold is an impor-
tant structural organization (assembly) present in a number
of pheromones and natural products such as frontalin, bre-
vicomin, multistriatin, bullerone, and palytoxin.[3] Frontalin
(1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane) is the aggrega-
tion pheromone of pine beetles of the Dendroctonus fam-
ily.[4] This pheromone has also been isolated from the bark
of several angiosperm trees[5] and from the temporal gland
of the male Asian elephant during sexual activity.[6] These
compounds are now successfully used to control the pro-
gression of pine beetle infestations in forests.[4] Therefore, a
great deal of effort is now being spent to develop concise
and rational approaches to the synthesis of frontalin and
its congeners.[4,7,8] However, most of the proposed strategies
are either multistep[9] or require hardly accessible starting
materials.[3,10] Our serendipitous discovery of the one-pot
assembly of the frontalin scaffold originates a new synthetic
concept in this important area.
Scheme 1. The assembly of 7-methylene-6,8-dioxabicyclo[3.2.1]-
octanes 3a–e from ketones 1a–e and acetylene.
The structures of compounds 3a–e unambiguously fol-
low from the single-crystal X-ray diffraction of compound
3e (Figure 1) as a typical representative of this series. Its
structure is formed by one crystallographically independent
molecule, C18H20O2S2. In the dioxabicyclooctane fragment,
the dihedral angle formed by the O(1)O(2)C(8) and O(1)
C(3)O(2) planes equals 153.0°, the dihedral angle between
the O(1)O(2)C(8) and O(1)C(7)C(8) planes is 157.4°, and
the dihedral angle between the O(1)C(3)O(2) and O(1)C(7)
C(8) planes is 132.8°. The dihedral angle between the planes
of the thiophene heterocycles equals 98.3°. Torsion angles
in the dioxolane heterocycle are O(1)C(7)C(8)O(2) 22.5(1)°,
[a] A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences
1 Favorsky Str., 664033 Irkutsk, Russia
Fax: +7-3952-419346
E-mail: boris_trofimov@irioch.irk.ru
[b] Institute of Problems of Chemical Physics, Russian Academy of
Sciences
Acad. Semenov av. 1, Chernogolovka, Moscow region 142432,
Russia
[c] N. S. Kurnakov Institute of General and Inorganic Chemistry,
Russian Academy of Sciences
Leninsky prp. 31, Moscow 119991, Russia
Supporting information for this article is available on the
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5142–5145