Intramolecular CuCl-mediated oxidative coupling of alkenyltrimethylstannane functions: An effective method for the construction of carbocyclic 1,3-diene systems

Full text of DOI:10.1021/ja953648y

J. Am. Chem. Soc. 1996, 118, 1215-1216
1215
Scheme 1
Intramolecular CuCl-Mediated Oxidative Coupling
of Alkenyltrimethylstannane Functions: An
Effective Method for the Construction of
Carbocyclic 1,3-Diene Systems
Edward Piers* and Miguel A. Romero
Department of Chemistry, UniVersity of
British Columbia, 2036 Main Mall, UniVersity Campus
VancouVer, British Columbia, Canada V6T 1Z1
ReceiVed October 31, 1995
The discovery of new, efficient methods for the construction
of carbon-carbon bonds represents an ongoing, central theme
of research in the area of organic synthesis. In this context,
the palladium(0)-catalyzed intermolecular1,2 and intramolecular3
cross couplings of alkenyltrialkylstannane functions with alkenyl
triflates, iodides, or bromides constitute valuable processes for
the stereospecific preparation of acyclic and carbocyclic con-
jugated diene systems. A recent report4 from this laboratory
disclosed that intramolecular coupling of alkenyltrimethylstan-
nane moieties with alkenyl halide (Br, I) functions can also be
performed efficiently by treatment of the requisite substrates
with CuCl (∼2-3 equiv) in N,N-dimethylformamide (DMF).
We report herein the novel finding that CuCl also mediates the
highly efficient intramolecular coupling of two alkenyltrimeth-
ylstannane functions. As outlined below, this method has thus
far successfully effected the closure of 4-, 5-, 6-, 7-, and
8-membered rings.
The substrates 4-11 employed in this study were prepared
as summarized in Scheme 1. Treatment of the lithium enolate
of the â-trimethylstannyl R,â-unsaturated ester 15,6 with 0.5
equiv of dibromo Meldrum’s acid (13)8 provided the “dimeric”
substance 4.9,10 Alkylation of 1 with the allylic bromide 1411,12
provided the bis(alkenylstannane) 5, while similar reactions
involving 27 and the bromides 1411,12 and 1511,12 produced the
structurally related compounds 6 and 7. On the other hand,
alkylation of 1 and 2 with the allylic bromide 1612,13 and the
primary iodide 17,3a,12 respectively, gave the corresponding
functionalized substances 8 and 9.
of diethyl malonate with the bromide 1411,12 gave a mixture of
the di- and monoalkylation products 10 and 12, respectively.
Transformation of 12 into the bis(alkenylstannane) 11 was
achieved via a straightforward alkylation involving use of the
iodide 173a,12 as the electrophile.
The substrates 10 and 11 were also prepared via alkylation
chemistry (Scheme 1). Thus, reaction of the potassium enolate
(1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Mitchell, T. N. Synthesis 1992, 803.
(2) Scott, W. J.; Crisp, G. T.; Stille, J. K. Org. Synth. 1990, 68, 116.
(3) (a) Piers, E.; Friesen, R. W.; Keay, B. A. Tetrahedron 1991, 47,
4555. (b) Piers, E.; Friesen, R. W. Can. J. Chem. 1992, 70, 1204. (c) Piers,
E.; Friesen, R. W.; Rettig, S. J. Can. J. Chem. 1992, 70, 1385.
(4) Piers, E.; Wong, T. J. Org. Chem. 1993, 58, 3609.
(5) All new compounds reported herein exhibit spectra in accord with
assigned structures and gave satisfactory elemental (C, H) analyses and/or
molecular mass determinations (high-resolution mass spectrometry).
(6) Compound 1 was prepared from 2-ethoxycarbonylcyclohexanone via
a method similar to that described previously for the corresponding methyl
ester.7
Rapid addition of a solution of 4 (1 equiv) in N,N-
dimethylformamide (DMF, ∼4 mL per millimole of 4) to a
warm (∼60 °C), stirred slurry of CuCl (∼5 equiv) in DMF (∼4
mL per millimole of CuCl), followed by stirring of the mix-
ture for 15 min, produced the structurally novel tricycle 18 in
67% yield (Scheme 2). Since, at this stage, the relative
configurations of 4 and 18 were not known, the crystalline
product (mp 124-125 °C, from Et2O-pentane) was subjected
to an X-ray crystallographic study.14 It was thus established
conclusively that this material possesses the structure shown in
formula 18. Interestingly, in the solid state, the conjugated diene
system of 18 is notably twisted away from planarity; the tor-
sion angle traced in going from C-3 to C-12 (via C-2 and C-1)
is 66°.
The closures of 5-membered rings via the new coupling
method, using protocols very similar to those employed for 4,
are illustrated by the conversions of 5-8 into 19-22, respec-
tively. Each of these reactions is clean and efficient, and thus,
by use of experimentally undemanding chemistry, the syntheses
of functionalized tricyclo[7.4.0.02,7]tridecane (19), tricyclo-
(7) Piers, E.; Tse, H. L. A. Can. J. Chem. 1993, 71, 983.
(8) Bloch, R. Synthesis 1978, 140.
(9) The yield of this process, as well as that of each of the other
alkylations described herein, has not yet been optimized.
(10) Presumably, the enolate of 1 reacts with 13 to afford (primarily)
the 3-bromo derivative of 1, which then alkylates the γ-position of the
enolate to produce 4. This interesting transformation is currently being
studied in more detail. The relative configuration of 4 was determined by
an X-ray crystallographic study on the corresponding cyclization product
18 (vide infra).
(11) Reduction (i-Bu2AlH, THF) of the esters 1 and 2, followed by
treatment of the acquired alcohols with Ph3PBr2 in CH2Cl2 in the presence
of imidazole, provided the required allylic bromides 14 (86%) and 15 (92%),
respectively.
(12) Solutions (THF) of each of the alkylating agents employed in this
work were passed through a plug of dry basic alumina immediately prior
to use.
(14) Details of this X-ray crystallographic study will be presented
elsewhere. We are very grateful to Dr. Steven J. Rettig for carrying out
this structure determination.
(13) The bromide 16 was derived (Ph3PBr2 in CH2Cl2 in the presence
of imidazole, 85%) from the corresponding allylic alcohol.3c
0002-7863/96/1518-1215$12.00/0 © 1996 American Chemical Society

1216 J. Am. Chem. Soc., Vol. 118, No. 5, 1996
Communications to the Editor
Scheme 2
Scheme 3
diverse set of functionality. The efficient syntheses of the novel
substances containing 4-, 7-, and 8-membered rings (18, 24,
and 25, respectively) are particularly noteworthy. Obviously,
many extensions to this work can be envisaged, including the
prospect of using the methodology for the construction of larger
ring systems and for the syntheses of structurally novel natural
and non-natural products. We are actively pursuing a number
of possibilities.
At present, the mechanistic pathway followed by the new
cyclization method remains obscure. However, it has been
found that complete conversion of starting material to product
within a relatively short reaction time (e.g., 15 min) requires at
least 4 equiv of CuCl. We have routinely employed ∼5 equiv
of the Cu(I) salt. Furthermore, it was determined that, for each
millimole of substrate converted to product, 2 mmol of copper
metal is produced.15 Also, the presence of water in the reaction
mixture does not appear to have a deleterious effect on the
efficiency of the reaction. For example, treatment of substrate
6 with CuCl (5 equiv) in DMF (60 °C) containing 1 equiv of
water provided product 20 in 91% yield. Based on previous
studies,16,17 it is reasonable to propose that the cyclization
process is initiated by transmetalation of one of the Me3Sn
groups in the substrate (Scheme 3, general formula 26), to afford
Me3SnCl and the intermediate represented by the general
formula 27. A proposal regarding the mechanistic details of
the transformation of 27 into the product 28 with the ac-
companying formation of 2 equiv of copper metal will have to
await further experimentation.
[7.3.0.02,7]dodecane (20), tricyclo[6.3.0.02,6]undecane (21), and
bicyclo[4.3.0]nonane (22) ring systems are readily accomplished.
To demonstrate further the versatility and effectiveness of
the method, the possibility of forming 6-, 7-, and 8-membered
rings was investigated. These processes are exemplified by the
conversions of 9-11 into the corresponding dienes 23,3a 24,
and 25. It should be noted that, for each of the transformations
10 f 24 and 11 f 25, somewhat more dilute reaction mixtures
(0.017 mmol of CuCl per milliliter of DMF) were employed.
Furthermore, in each of these reactions, the solution of the
substrate in DMF was added slowly (over a period of ∼15 min)
to the mixture of CuCl and DMF, and, after the addition was
complete, stirring was continued for an additional 15 min.
Under these conditions, both reactions were highly efficient.
The results summarized above show clearly that the CuCl-
mediated intramolecular coupling of alkenyltrimethylstannane
functions constitutes an effective, potentially valuable method
for the synthesis of carbocyclic systems containing conjugated
diene units. Collectively, the products 18-25 display an
impressive array of carbon skeletons and, in addition, exhibit a
Acknowledgment. We are grateful to the NSERC of Canada for
financial assistance.
Supporting Information Available: Typical experimental proce-
dures describing the preparation of 15 from 2, the use of 2 and 15 to
prepare 7, and the CuCl-mediated ring closure of 7 to 21 (3 pages).
This material is contained in libraries on microfiche, immediately
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JA953648Y
(15) The effect of using varying amounts of CuCl on conversion of
starting material into product, and the quantification of the amount of copper
metal produced during the cyclization process, were determined by studying
the transformation of 6 into 20. Details of these investigations will be given
in a full account of this work.
(16) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S.
J. Org. Chem. 1994, 59, 5905.
(17) Piers, E.; McEachern, E. J.; Burns, P. A. J. Org. Chem. 1995, 60,
2322.