Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 3531-3532
NOTE
Novel Synthesis of Kahweofuran: A Flavour Component of Roasted Coffee
WEILI LI
Department of Chemistry, Kunming University; No. 2, Puxin Road, Kunming High and New Tech Development Zone, Kunming 650214,Yunnan
Province, P.R. China
Corresponding author: Tel: +86 871 5098476; E-mail: lierkm@163.com
(Received: 2 April 2012;
Accepted: 29 December 2012)
AJC-12640
Kahweofuran (1), one of the impact flavours of roasted coffee and possesses 6-methyl-2, 3-dihydrothieno[2,3-c]furan structure, was obtained
from 4,5-dihydrothiophen-3(2H)-one through six steps.
Key Words: Kahweofuran, Flavour, Palladium-catalyzed inserting reactions.
Kahweofuran (1) was characterized1 40 years ago, as one
Br
Br
S
Br
S
of the impact flavour components of roasted coffee and its
structure was determined2 in 1971 by spectroscopy and
synthesis. However, a full evaluation of its aromatic significance
is apparently still lacking because it is not easily synthesized.
Four approaches to the carbon-7 framework of 1 have
been reported (Scheme-I). In order to identify the structure of
kahweofuran, Buchi's group2 reported its synthesis starting
from 3-ketotetrahydro thiophene (2) by acylation and the
Grignard reaction followed by acid treatment. Although this
synthesis involve only three steps, the reported acylation
reaction lack specificity and thus difficult isomeric separations
are required and the overall yield was only 2 %. Gorzynski's
group3 prepared kahweofuran 1 from 3,4-dibromofuran 3, from
which the C-7 framework derivative 4 was obtained through
two C-C bond forming reactions based on carbanion chemistry.
Although this synthesis was only four steps, these know
procedures still afforded low overall yields. To avoid the diffi-
culty of isomeric separation, Brenna's group4 also prepared
kahweofuran 1 from α-methylcinnamaldehyde with dimethyl
succinate. Although this synthesis avoided the difficulty of
isomeric separation, its synthetic route was too long in fourteen
steps. Other synthesis was also unsatisfactory from the view-
point of efficiency and yield5. Thus, more efficient and rapid
synthesis of kahweofuran was exactly desired and here we
reported the novel synthesis of kahweofuran.
Br
O
O
1
O
3
O
2
4
Scheme-I
the corresponding ester 5 in 78 % yield as colourless oil, which
was inserted with carbon monoxide through palladium-
catalyzed process7 to afford an oil 6 in 86 % yield. Ester 6 was
quantitatively reduced with LiAlH4 in THF to corresponding
alcohol 7 as colourless oil, whose hydroxyl group was
protected with 3,4-dihydro-2H-pyran to afford the ether 8 as
an colourless oil in 96 % yield8. Regioselective generation of
and anion at the 2-position9 of the ether 8 was successful by a
chelation-controlled effect with the 3-hydroxymethyl tetra-
hydropyranyl ether.Although the reaction of the corresponding
anion with acetic anhydride gave the desired 2-acetylated
compound 9 in 26 % yield, rapid addition of N-methoxy-N-
methylacetamide instead of acetyl chloride into the anion
solution at -78 ºC afford the desired acetylated compound 9 in
68 % yield. Treatment of compound 9 with a catalytic amount
of dilute sulphuric acid in boiling THF to remove the DHP
group and meanwhile the corresponding hydroxyketone
proceeded ring close to form kahweofuran (1) in 27 %
overall yield. Based on the spectral data of 9 the structures of
compound 1, 5-9 were proposed as shown in Scheme-II.
We selected 3-ketotetrahydro thiophene (2) as a suitable
starting material because it contains the thiophene ring.
Ketone 2 was enolized6 and the enolate was trapped with
trifluoroacetic anhydride in dichloromethane at 0 ºC to afford
Conclusion
In summary, the synthetic sequences of kahweofuran (1)
described all the reactions involved are regiospecific. Moreover,