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J.
CHEM.
SOC.,
CHEM.
COMMUN.,
1987
907
Studies
on
the Reactivity
of
2-Furylhydroxymethylphosphonates:
Synthesis
of
1
-0xo-4-
hydroxycyclopent-2-en-5-ylphosphonates
Enzo Castagnino,a Maurizio D'Auria,b Antonella De Mico,b Franco D'Onofrio,b and Giovanni Piancatellib"
a
lstituto di Chimica Farmaceutica e Tecnica Farmaceutica, Universita degli Studi,
06100
Perugia, ltaly
b
Centro
C.N.R.
di Studio per la Chimica delle Sostanze Organiche Naturali, c/o Dipartimento di Chimica, Universita
'La
Sapienza,' P.le
A.
Moro
2,
00185
Roma, ltaly
Starting from
2-furylhydroxymethylphosphonates
(l),
a
facile and direct preparation
of
the previously unknown
phosphonate-containing cyclopentenones
(5),
potential new synthons in the elaboration
of
rethrolone- and
prostaglandin-related compounds,
is
described.
Our interest in the chemistry of
2-furylhydroxymethylphos-
phonates (1) has led
us
recently to show their use as valuable
starting materials in a simple synthesis of several compounds
which had not been described before.1 During the course of
this investigation, we observed that 2-furylhydroxymethyl-
phosphonate
(la)
(RI
=
R2
=
R3
=
H),
by treatment with
1.25
M
HCI
in acetone at
58
"C
for
8
h, furnished the levulinic
acid derivative
(2),
a Marckwald-type product;z
on
the other
hand, its 5-methyl derivative, under the same conditions, gave
diethyl2,5-dioxohex-3-enylphosphonate
(3),
showing that the
reactivity was dependent on the substituent pattern
on
the
furan ring.
Prompted by these findings, we considered it advantageous
to exploit the influence of a more efficient leaving group in the
side chain on the reactivity, in order to broaden the usefulness
of these compounds in organic chemistry. We now report a
new application
of
2-furylhydroxymethylphosphonates
(1)
,
as
good starting materials for a facile preparation of the
J.
CHEM.
SOC.,
CHEM.
COMMUN.,
1987
908
Scheme 1.
i, HCl
(1.25
M),
Me2C0, 58 "C, 8 h; ii,
0
Me-CO-CH=Cfi-
CO-CH,-
PO(OEt),
(3)
Et3N, MeSO2C1, room temp.; iii, DME-H20 (9:
l),
room temp.; iv, MeS0,CI; v, H20.
Table 1.
Experimental conditions in the conversion
(1)
+
(5),
see Scheme
1.
Reaction Reaction
Yo
Entry Substrate R1 R2 R3 time/h Producta time/h Product Yieldb
1
(la)
H H H 18
(44
48=
(5a)
54
2
(lb)
H
Br
H 4
(4b)
96
(5b)
60
3
(lc)
H H Br
1
(4c) (5c)
78
4
(Id)
Me Br H
1
(44
24c
(5d)
33
a
Chlorides (4a-4) were used without further purification in the subsequent reaction (see text).
b
The yields, calculated
on
the compounds
(la-d),
refer to isolated, chromatographically pure, products.
c
Buffer solution (AcOH-AcONa, pH 4.7) was used.
d
SiO,-EtOAc.
previously unknown phosphonate-containing cyclopenten-
ones of type
(5),
which are very promising as synthetic tools in
the elaboration of natural products.
In our experiments we utilized the chloride ion as the
leaving group and compounds (4) were readily prepared by
reaction of the corresponding alcohol
(1)
with MeS02C1 in the
presence of Et3N under dry conditions.3 We found it more
convenient and cheaper to use (4) without further purification
since they tended to decompose during the purification
procedure. The results are summarised in Table 1.
The molecular rearrangement of chlorides (4a-d) into
l-oxo-4-hydroxycyclopent-2-en-5-ylphosphonates
(5a-d)
occurred readily under solvolytic conditions [0.04
M
solution
of
(44)
in dimethoxyethane (DME)-water
(9:
l)].
However in some cases (Table
1,
entries
1
and 4),
HCI
evolution during the reaction led to decomposition of both
substrates and products and an appropriate buffer solution
had to be used to prevent a drastic fall in pH.
All the reactions proceeded in a stereospecific manner: in
fact, the cyclopentanone (Sa) showed in the 1H n.m.r. spectra
a
trans
coupling constant value between the protons at C-4 and
C-5
(J
2
Hz), in accordance with previously reported data for
these compounds.4 The conversion
(4c)
-+
(5c)
(Table
1,
entry
3)
occurred after adsorption of the chlorination reaction
mixture onto a short pad
of
silica gel and subsequent elution
with ethyl acetate. The low yield of the isolated product
(5d)
(Table
1,
entry
4)
is due to extensive decomposition during
purification. The presence of a bromine atom at
C-3
or C-4 on
the furan ring did not affect the molecular rearrangement: it
appeared to stabilise the final product (Table
1,
entries
2
and
3).5
The dibromo substituted derivative furnished directly the
expected product
(6)
as a stereoisomeric mixture, in very high
yield (Scheme l).4
In conclusion, the ready preparation of compounds
(5)
in
good yields by a mild and effective procedure makes these
compounds potential new synthons for the synthesis of
biologically active natural products.
Received,
22nd January
1987;
Corn.
080
References
1
E. Castagnino,
S.
Corsano, and
G.
Strappaveccia,
Tetrahedron
2
G.
Piancatelli and
E.
Castagnino,
Heterocycles,
1985,
23,
667.
3 M.
E.
Evans, L. Long, Jr., and
F.
W.
Parrish,
J.
Org.
Chem.,
1968,
4
G.
Piancatelli,
A.
Scettri, and
S.
Barbadoro,
Tetrahedron Lett.,
5
M. D'Auria,
F.
D'Onofrio,
G.
Piancatelli, and A. Scettri,
Gazz.
Lett.,
1985, 93.
33,
1074.
1976,3555.
Chim. Ital.,
1986,
116,
173.
