PREPARATION OF HIGHLY FUNCTIONALIZED 3,4-DISUBSTITUTED CYCLOBUTENE-1,2-DIONES USING FUNCTIONALIZED ZINC-COPPER ORGANOMETALLICS

Article abstract of DOI:10.1016/S0040-4039(00)60811-0

The selective substitution reactions of the zinc-copper reagents with 3,4-dichlorocyclobutene-1,2-dione 2 allows to prepare a variety of new functionalized symmetrical and mixed 3,4-disubstituted cyclobutene-1,2-diones of type 3 and 4. Key words: zinc-copper organometallics, cyclobutene 1,2-diones, functionalized organometallic reagents.

Full text of DOI:10.1016/S0040-4039(00)60811-0

Vol. 33, No. 49, PP. 7515-7X8.1992
in Great Britain
+
PREPARATION OF HIGHLY FUNCTIONALIZED
DISUBSTITUTED
USING
FUNCTIONALIZED ZINC-COPPER
Nicole
Richard M.
and Paul
Department of Chemistry and Department of Material Science
The University of Michigan, Ann Arbor, Michigan 48109
Fachbereich Chemie,
3550
Germany
Key words: zinc-copper
cyclobutene
functionalized organometallic reagents.
Summary: The selective substitution reactions of the zinc-copper reagents with
2 allows to prepare a variety of new functionalized symmetrical
and mixed
of type 3 and 4.
Synthetic method8 for the preparation of
been developed by a number of research groups due to the importance of these compounds as
building blocks for organic and for the preparation of new
have
We wish now to report a new approach to highly functionalized
cyclobutene-1 by using the addition of functionalized zinc-copper reagents
to the readily available
2. Depending on the
nature of the reagents
1
and on the stoechiometry used, either symmetrical cyclobutenediones 3
or unsymmetrical cyclobutenediones 4 are obtained in fair to good yields (eq. 1).
0
1)
2)
FG-R
R-FG
3
2
4
7515

7516
Thus, the addition of
2 (1 .O equiv.) to a THF solution of a
2 h) affords
functionalized copper-zinc reagent FG-RCu(CN)Znl (ca. 3 equiv.) at -78°C (then
the desired symmetrical di-coupling products
in 87-89% isolated
see eq. 1 and Table
Table Symmetrically functionalized
the reaction of
cyclobutene-1
2 with
obtained by
1.
Yield
Entry
RCu(CN)ZnX
Product
of type 3
3a
3b
3c
3d
81
79
67
78
la
lb
Ic
2
3
4
he
5
8
le
I
83
7
8
lg
lh
3h
9
72
li
31
All yields refer to isolated yield of analytically pure compounds
Remarkably, a wide range of functionalities (alkyne (entries 1 and
ester (entries 6 and
halide (entry
(entry 8) and ketone (entry 9) are tolerated in the organometallic reagents
1, allowing a unique access to functionalized
of type 3. A selective
replacement of one chlorine atom of 2 is possible and the addition of the copper reagents derived
respectively from cyclohexenylzinc iodide and 3-carbethoxypropylzinc iodide provides the
expected
42 and 52%). An important side product (up to 40% in the case of
symmetrical of type 3. A better procedure consists of adding sequentially to the dichloride
2 (1.0 equiv.) two different copper reagents (ca. 1.2 equiv, to 4h)
5 in moderate yields (respectively
is the corresponding
and
(ca. 1.8 equiv. -78” to
1 h). In this one-pot procedure the sensitive
5 are generated in situ and are reacted directly
mono-substituted
with an excess of the second zinc-copper reagents
tertiary group, then good overall yields of the mixed disubstituted cyclobutenediones 4 are
obtained; see eq. and Table 2).
If
is a secondary or

7517
Table 2. Mixed disubstituted
4 obtained by the sequential reaction of
2 with two different copper zinc reagents
and
Yield
Product of
Entry
type
4
74
67
65
57
81
4a
4b
4c
4d
c-Hex
c-Hex
c-Hex
c-Hex
t-Bu
1
2
3
4
5
6
77
t-Bu
All yields refer to isolated yields of anal ytically pure products.
In summary, we have shown that symmetrical and mixed polyfunctional
of type 3 and 4 can be readily prepared. The use of these and related
cyclobutenes for the preparation of new polymers is currently investigated.
Acknowledgements: We thank the Chemistry Department of the University of Michigan,
and the Air Force Office of Scientific Research for support of this work.
References and Notes
1.
2.
For an excellent review on the preparation of squaric acid derivatives: Schmidt, A.H.
Synthesis 961.
(a) Decker, O.H.W.; Moore, H.W. Org. Chem.
J.O.; Perri, S.T.; R.; Xu, S.L.; Patil, S.; Moore, H.W. Am. Chem.
52, 1174; (b) Foland, L.D.; Karlsson,
111, 975; (c) Foland, L.D.; Decker, O.H.W.; Moore, H.W.
Am. Chem.
112, 8612; (e) Liebeskind,
53, 2482; Liebeskind,
31, 4293; (g) Liebeskind, L.S.; Fengl, R.W. Org.
55, 5359; (h) Liebeskind, L.S.; Granberg, K.L.; Zhang, J. Org. Chem.
111,
989; (d) Liebeskind, L.S.; Foster, B.S. Am. Chem.
L.S.; Fengl, R.W.;
K.R.; Schawe, T.T. J. Org. Chem.
L.S.; Wang, J. Tetrahedron
Chem.
3.
(a)
Y.; Knobler, C.B.; Diederich, F.
Knobler, C.B.; Anthony, J.;
(c) Wegner, G. Angew. Chem.
Am. Chem.
112, 1607; (b)
Y.; Lin,
A.M.; Diederich, F. Am. Chem.
93,352.
4.
(a) Knochel, P.; Yeh, M.C.P.; Berk, SC.;
Knochel, P.; Rozema, M.J.; Tucker, C.E.;
J. J. Org. Chem.
C.; Furlong, M.;
53, 2390; (b)
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Chem.
64,361 and references cited therein.

7518
5.
(a) De
R.C.; Fox, C.J.; Riordan, R.C. Tetrahedron
New Series 15, 119.
781; (b) Argyropoulos,
(entry 6
N.G. Chimika
Typical procedure: Preparation of
of Table 1). A THF solution of
6.
acetate (3.1 g, 12 mmol in 6
of THF) was
added
dibromoethane and
and the excess of zinc dust was decanted. The clear solution of
at 35°C to zinc dust (2.4 36 mmol) which had been activated with
according to ref. 4a. The reaction mixture was stirred for 2 h at
iodide was added at
mmol), (1.0 g, 24 mmol) and THF (10
mixture was cooled to -70°C and
to a THF solution of
(made from
(1.06 12
After stirring for 5 min at
the reaction
(604 mg, 4 mmol) in
THF (3
to
was added. After 2 h at this temperature, the resulting red solution was warmed
stirred for 2 h at this temperature and worked up as usual. The resulting crude oil
was purified by flash-chromatography using
pure (1.21 g, 89% yield).
affording analytically
7.
Typical Procedure: Preparation of
dione 4a (entry 1 of Table 2). Cyclohexylzinc iodide prepared from cyclohexyl iodide (1.47
7 mmol), zinc dust (1.3
THF solution of
20 mmol) in THF (7
at
(2 h) was added at -10°C to a
(540 mg, 6 mmol) and
(500 mg, 12 mmol). The resulting
solution was stirred 5 min at 0°C and cooled to -70°C and a solution of
(755 mg, 5 mmol) in THF (7 was slowly added. The
reaction mixture was stirred 4 h at -40°C to -60°C cooled to -70°C and the copper reagent
derived from
iodide (prepared from ethyl 4-iodobutyrate (2.42 10
(900 mg, 10 mmol), (840 mg, 20 mmol) in 7 and 10
mmol) zinc (2.0
30 mmol),
of THF; see above) was added. The reaction mixture was slowly warmed to 0°C and
stirred for 1 h at this temperature. After the usual workup, the crude residual oil was purified
by flash chromatography affording first 0.3 g (24%) of
(hexane), followed by 1.034 g (74% yield) of the desired mixed
48
=
(Received in Germany 26 August 1992)