A remarkably efficient synthesis of pure cis-stilbenoid hydrocarbons using trans-dibromoalkenes via palladium catalysis

Article abstract of DOI:10.1021/ja027421w

A remarkably versatile synthesis of cis-stilbenoid hydrocarbons containing highly functionalized phenyl groups is developed via an efficient palladium-catalyzed coupling of aryl Grignard reagents with trans-1, 2-dibromoalkenes (generally obtained via brom

Full text of DOI:10.1021/ja027421w

Published on Web 11/23/2002
A Remarkably Efficient Synthesis of Pure cis-Stilbenoid Hydrocarbons Using
trans-Dibromoalkenes via Palladium Catalysis
Rajendra Rathore,* Mihaela I. Deselnicu, and Carrie L. Burns
Marquette UniVersity, Department of Chemistry, PO Box 1881, Milwaukee, Wisconsin 53201-1881
Received June 23, 2002
Table 1. Pd-Catalyzed Coupling of ArMgBr with
cis-Stilbenoid hydrocarbons containing highly substituted phenyl
groups (such as pentamethylphenyl) form molecular clefts that are
especially efficacious for trapping small analytes such as nitric oxide
and metal cations.1-3 These hydrocarbons are also potentially useful
as photochromic molecular switches for molecular-electronics
applications.4 Despite the extensive need for such molecules, there
are no reported general procedures for preparation of pure cis-
stilbenoid frameworks. Synthesis of highly substituted stilbenoid
hydrocarbons is generally accomplished by using either McMurry
coupling or the dimerization of carbenes in rather minuscule yields.5
It is noteworthy that these procedures are nonstereospecific and
thus produce mixtures of cis- and trans-stilbenes.
trans-Dibromoalkenesa
Presently, palladium catalysts are extensively investigated be-
cause of their important role in the formation of C-C bonds,
especially between sp2-hybridized carbons.6 We have recently
observed that the cis-1,2-dibromobicyclo[2.2.2]oct-2-ene undergoes
an efficient coupling with various aryl Grignard reagents in the
presence of bis(triphenylphosphine)palladium dichloride to afford
1,2-diarylbicyclo[2.2.2]oct-2-enes in excellent yields7 (eq 1).
Unfortunately, only a handful of cis-dibromoalkenes are known
which are generally prepared via multistep synthetic procedures.8
In sharp contrast, the trans-1,2-dibromoalkenes with a broad array
of substituent are readily available from a simple bromination of
the corresponding acetylenes.9
We now report that, under reaction conditions depicted in eq 1,
the coupling of aryl Grignard reagents (bearing ortho methyl groups)
with acyclic trans-1,2-dibromoalkenes readily affords in each case
a single isomer of pure cis-1,2-diarylalkenes (vide infra) in nearly
quantitative yields (see Table 1), for example, eq 2
a All reactions were performed using the general procedure (see text).
b Progress of the reactions was monitored by GC and TLC. c Isolated yield.
(50 mL) and extracted with dichloromethane (3 × 50 mL). Drying
of the organic layer and evaporation of the solvent, followed by
recrystallization from ethanol-dichloromethane mixture afforded
bis-4,5-(pentamethyl-phenyl)oct-4-ene (6) in essentially quantitative
yield (49.2 mmol, 98%).
The generality of this surprisingly simple procedure (in eq 2) is
demonstrated by the preparation of a variety of cis-stilbenoid
hydrocarbons having different substituents (see Table 1). Moreover,
it is important to emphasize that this synthesis of cis-diarylalkenes,
according to the general procedure described above (eq 2 and Table
General Procedure. In a typical procedure, a freshly prepared
solution of pentamethylphenylmagnesium bromide (1.0 M, 105
mmol) was mixed with a solution of trans-4,5-dibromooct-4-ene
(50 mmol) in anhydrous tetrahydrofuran (50 mL) containing a
catalytic amount of bis(triphenylphosphine)palladium(II) chloride6a
(0.1 mol %) under an argon atmosphere at 25 °C. The resulting
pale-yellow solution was refluxed for 8-16 h and cooled to room
temperature. The resultant reaction mixture was diluted with water
* Corresponding author. E-mail: rajendra.rathore@mu.edu.
9
14832
J. AM. CHEM. SOC. 2002, 124, 14832-14833
10.1021/ja027421w CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
diarylalkene 5 and none of the monoarylated bromoalkene could
be detected by a careful GC and GC/MS analysis. While a detailed
study of the mechanism of this reaction is in progress, these
preliminary experiments suggest that the coupling of two aryl groups
to the trans-dibromoalkenes (in the presence of a palladium catalyst)
is either simultaneous or that the addition of second aryl group is
much faster than the first one.
In summary, we have developed a novel and versatile procedure
for the preparation of pure cis-diarylalkenes from readily available
trans-dibromoalkenes. We believe that this new versatile synthesis
of cis-stilbenoid hydrocarbons will allow the exploration of these
novel cleft-containing materials for the development of practical
optoelectronic devices for the detection and quantification of various
analytes such as NO, NO2, Ag+, and so forth.
Figure 1. ORTEP diagrams of bis(pentamethylphenyl)-octene 6 (left) and
bis(pentamethylphenyl)phenylhexene 7 (right) showing the cis-juxtaposition
of pentamethylphenyl moieties.
Scheme 1. Synthesis of Multichromophoric Stilbenoid
Hydrocarbons
Acknowledgment. We thank the Petroleum Research Fund
(AC12345) for financial support and Dr. Ilia A. Guzei (UW,
Wisconsin) for the X-ray crystallography. C.L.B. thanks the
Department of Education for a GAANN fellowship.
Supporting Information Available: Experimental procedures and
spectral data for 1-13 (PDF) and the X-ray crystallographic data for
6 and 7 (PDF/CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
1), did not produce even a trace amount of the trans-isomer in all
cases. The structures of various cis-diarylalkenes were established
by NMR spectroscopy10 and further confirmed by X-ray crystal-
lography (see Figure 1 for representative X-ray structures11).
The versatility of this simple procedure is further demonstrated
by an easy three-step preparation of bichromophoric stilbenoid
ligands 13a and 13b from readily available starting materials (see
Scheme 1 and Supporting Information). These ligands contain
multiple stilbenoid clefts which are especially efficacious for
binding a variety of metal cations and other analytes such as NO
and NO2.3 For example, bifunctional ligands 13a and 13b readily
incorporate two metal cations, such as Ag+, with high binding
efficiency.12 We are currently exploring the physical and chemical
properties of these materials for potential usage as molecular
switches and intervalence compounds.13
Such a remarkably efficient and quantitative isomerization of a
trans-alkene to the corresponding cis-diarylalkene, during the aryl
coupling, in the presence of a catalytic amount (0.1 mol %) of
(PPh3)2Pd(II)Cl2 in eq 2 is unprecedented. It is, however, important
to note that the success of this transformation (eq 2) clearly depends
on the presence of ortho methyl groups on the aryl Grignard reagent.
For example, when the reaction of trans-dibromoalkenes is carried
out with arylmagnesium bromides lacking ortho substituents, they
produced largely (>95% yield) the corresponding biaryls and
dialkylacetylene, for example, eq 3.14
References
(1) (a) Rathore, R.; Lindeman, S. V.; Kochi, J. K. Angew. Chem., Int. Ed.
1998, 37, 1585. (b) Rathore, R.; Lindeman, S. V.; Rao, K. S. S. P.; Sun,
D. Angew. Chem., Int. Ed. 2000, 39, 2123 and references therein.
(2) (a) Gano, J. E.; Subramanian, G.; Birnbaum, R. J. Org. Chem. 1990, 55,
4760. (b) Lindeman, S. V.; Rathore, R.; Kochi, J. K. Inorg. Chem. 2000,
39, 5707 and references therein.
(3) Various highly substituted stilbenoid hydrocarbons in Table 1 effectively
bind NO and NO2 upon oxidative activation. Rathore, R.; Deselnicu, M.
I. (unpublished results).
(4) (a) For a recent review, see: Masahiro, I. Chem. ReV. 2000, 100, 1685
and references therein. (b) Also see: Introduction to Molecular Electron-
ics; Petty, M. C., Bryce, M. R., Bloor, D., Eds.; Oxford University Press:
New York, 1995.
(5) (a) Nazran, A. S.; Griller, D. J. Chem. Soc., Chem. Commun. 1983, 850.
(b) Tomioka, H.; Okada, H.; Watanabe, T.; Banno, K.; Komatsu, K.; Hirai,
K. J. Am. Chem. Soc. 1997, 119, 1582. (c) Lenoir, D.; Lemmen, P. Chem.
Ber. 1980, 113, 3112. (d) Bottino, F. A.; Finocchiaro, P.; Libertini, E.;
Reale, A.; Recca, A. J. Chem. Soc., Perkin Trans. 2 1982, 77 and
references therein.
(6) Reviews: (a) Kumada, K. Pure Appl. Chem. 1980, 52, 669. (b) Wolfe, J.
P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998,
31, 805. (c) Larock, R. C. AdV. Met.-Org. Chem. 1994, 3, 97. (d) Larock,
R. C. Pure Appl. Chem. 1990, 62, 653. (e) Poli, G.; Giambastiani, G.;
Heumann, A. Tetrahedron 2000, 56, 5959. (f) Li, G. Y. I. Organomet.
Chem. 2002, 635, 63 and references therein.
(7) Rathore, R.; Kochi, J. K. Can. J. Chem. 1999, 77, 1.
(8) (a) Komatsu, K.; Aonuma, S.; Jinbu, Y.; Tsuji, R.; Hirosawa, C.; Takeuchi,
K. J. Org. Chem. 1991, 56, 195. (b) Fry, A. J.; Farnham, W. E.; Holstein,
B. J.; Mitnick, M. A.; Riggs, L. C. J. Org. Chem. 1969, 34, 4195. (c)
Voigt, K.; Zezschwitz, P. v.; Rosauer, K.; Lansky, A.; Adams, A.; Reiser,
O.; de Meijere, A. Eur. J. Org. Chem. 1998, 1521, 1 and references therein.
(9) Pincock, J. A.; Yates, K. Can. J. Chem. 1970, 48, 3332.
(10) It is noteworthy that the chemical shifts for the methylene protons of the
alkyl groups in cis-stilbenoid hydrocarbons are shifted downfield as
compared to the corresponding trans analogues; see: Leimner, H.;
Weyerstahl, P. Chem. Ber. 1982, 115, 3697.
This transformation in eq 3 is in sharp contrast with the reactions
(11) X-ray crystallography data for 6 and 7 are on deposit with Cambridge
Crystallographic Data Center as supplementary publication nos.
CCDC169899 and CCDC169900, respectively.
presented in eq 1 with cis-1,2-dibromobicyclooctene and other cis-
dibromoalkenes,15 which yield the cis-diarylalkenes with both
unsubstituted and substituted arylmagnesium bromides in excellent
yields.
(12) Bifunctional ligands 13a-b readily incorporate two Ag+ cation in the
stilbenoid clefts as judged by the simple 1H NMR spectra, which suggest
that two Ag+-bound stilbenoid moieties are chemically equivalent in
solution at 22 °C. An X-ray crystallographic study in progress will establish
this point.
Moreover, the reaction with cis-dibromoalkenes15 proceeded in
a stepwise manner, that is, first one aryl group adds to yield
1-bromo-2-arylcycloalk-1-ene followed by the coupling of the
second aryl group to afford 1,2-diarylcycloalk-1-ene. Contrastingly,
when a reaction of pentamethylphenylmagnesium bromide was
carried out with an excess of trans-dibromohexene (100 fold)
according to the general procedure in eq 2, it yielded only the cis-
(13) Preliminary electrochemical and UV-vis spectral studies on 13a-b
suggest that a single hole (formed by removal of an electron) is delocalized
over both stilbenoid moieties; Rathore, R.; Deselnicu, M. I.; Burns, C. L
(unpublished results).
(14) The structure of the trace amount of cis-3,4-ditolylhex-3-ene obtained in
eq 3 was established by comparison with an authentic sample.10
(15) 1,2-Dibromocyclohex-1-ene and 1,2-dibromocyclopent-1-ene showed
reactivity analogous to that of 1,2-dibromobicyclooct-2-ene (see eq 1).
JA027421W
9
J. AM. CHEM. SOC. VOL. 124, NO. 50, 2002 14833