New one-pot synthesis of (E)-β-aryl vinyl halides from styrenes

Article abstract of DOI:10.1021/ol901233j

A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)-β-aryl vinyl iodides and (￡)-β-aryl vinyl bromides from styrenes based on sequential ruthenium-catalyzed silylative coupling-N-halosuccinimide-mediated halodesilylation reactions is reported.

Full text of DOI:10.1021/ol901233j

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3390-3393
New One-Pot Synthesis of (E)-ꢀ-Aryl
Vinyl Halides from Styrenes
Piotr Pawluc´,* Grzegorz Hreczycho, Justyna Szudkowska, Maciej Kubicki, and
Bogdan Marciniec*
Department of Organometallic Chemistry, Faculty of Chemistry, Adam Mickiewicz
UniVersity, Grunwaldzka 6, 60-780 Poznan, Poland
marcinb@amu.edu.pl
Received June 3, 2009
ABSTRACT
A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)-ꢀ-aryl vinyl iodides and (E)-ꢀ-aryl vinyl bromides from styrenes
based on sequential ruthenium-catalyzed silylative coupling-N-halosuccinimide-mediated halodesilylation reactions is reported.
Stereodefined ꢀ-aryl vinyl halides have been widely applied
as extremely useful building blocks in transition-metal-
catalyzed organic transformations and natural product syn-
thesis.1
Terminal alkynes can often serve as convenient starting
materials for the preparation of (E)-haloalkenes via a
hydrometalation/halogenation reaction sequence. Sterochemi-
cally pure (E)-ꢀ-aryl vinyl halides are obtained by two-step
procedures starting from aryl-substituted alkynes and involv-
ing vinylboranes,6 vinylsilanes,7 vinylstannanes,8 or vinylzir-
conium species9 as intermediates.
Classical methods for preparation of (E)-ꢀ-aryl vinyl
halides are based on the Takai olefination of aromatic
aldehydes2 or the Hunsdiecker reaction involving the halo-
decarboxylation of cinnamic acid derivatives.3 Alternatively,
(E)-ꢀ-aryl vinyl halides may be formed by the stereoselective
reduction of 1,1-dihaloalkenes4 or homologation of benzyl
bromides with dihalomethanes.5
Since the number of commercially available substituted
styrenes far exceeds that of phenylacetylenes, and the former
are much cheaper than their ethynyl analogues,10 the
development of new and straightforward synthetic methods
(1) Tsuji, J. In Reactions of Organic Halides and Pseudohalides,
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Wiley: New York, 2000; pp 27-108.
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Aoyama, T. Synthesis 2004, 7, 986–988.
10.1021/ol901233j CCC: $40.75
Published on Web 07/02/2009
 2009 American Chemical Society

for their direct conversion to stereodefined (E)-ꢀ-aryl vinyl
halides is of great significance.
On the other hand, it was found that electrophilic bromi-
nation (or iodination)18 of substituted styrylsilanes proceeded
stereoselectively with molecular halogens7,19 or N-halosuc-
cinimides20 to give the corresponding styryl halides with
retention of configuration.
We have envisaged that the ruthenium-catalyzed (E)-
selective silylative coupling of styrenes with trimethylvinyl-
silane followed by N-halosuccinimide-mediated halodesily-
lation can be a valuable synthetic method for one-pot
conversion of styrenes into (E)-ꢀ-aryl vinyl halides (Scheme
1). Therefore, in this paper, we report a facile one-pot
However, the stereoselective, direct transformations of
terminal alkenes into (E)-vinyl halides are strongly limited,
and to the best of our knowledge, there is no precedent for
the one-pot (E)-selective iodination of terminal alkenes.
Grubbs and co-workers reported a two-step synthesis of (Z)-
vinyl bromides and (E)-vinyl iodides from alkenes via their
sequential cross-metathesis with vinyl- or 1-propenyl bor-
onates followed by halogenation of the resulting alkenylbo-
ronate intermediates.11 However, iodination, in contrast to
bromination, cannot be carried out in one pot with a cross-
metathesis reaction. Very recently, the first example of cross-
metathesis of 4-methoxystyrene with (E)-1,2-dichloroethene
to yield (Z)-4-methoxystyryl chloride as predominant product
has been reported.12 (E)-Vinyl iodides can be also formed
by the two-step oxidative cleavage of the terminal olefins
with ozone or OsO4/NaIO4 followed by a Takai iodoolefi-
nation.13
Scheme 1. Proposed Synthesis of (E)-ꢀ-Aryl Vinyl Halides
The silylative coupling of olefins with vinyl-substituted
organosilicon compounds, which we have developed in the
last two decades as a new effective catalytic activation of
the C-H bond of olefins and C-Si bond of organosilicon
compounds (generally occurring in the presence of complexes
containing initially or generating in situ M-H and M-Si
bonds), appears to be a valuable synthetic tool in the
preparation of vinyl-substituted organosilicon reagents and
polymers.14 Recently, the ruthenium-catalyzed silylative
coupling reaction followed by Hiyama coupling has been
also successfully applied to the stereoselective synthesis of
organic products such as (E)-stilbenes15a and (E)-N-
styrylcarbazoles.15b,c
preparation of (E)-ꢀ-aryl vinyl iodides and (E)-ꢀ-aryl vinyl
bromides from styrenes via the corresponding (E)-styrylsilane
intermediates.
Initially, we focused on the synthesis of (E)-aryl vinyl
iodides, as they generally display higher activity in cross-
coupling reactions.
The reaction conditions were optimized with use of styrene
and trimethylvinylsilane as substrates. For preliminary results
on the silylative coupling reaction, equimolar amounts of
the comercially available styrene and trimethylvinylsilane
were used, and the reaction was conducted following the
original procedure (RuHCl(CO)(PPh3)3 catalyst (1 mol %)
toluene, 6 h, 100 °C, sealed ampule)16a to give exclusively
(E)-styryltrimethylsilane (GC yield >99%). Treatment of (E)-
styryltrimethylsilane with 2 equiv of N-iodosuccinimide
(NIS) in acetonitrile at room temperature according to the
method described by Kishi and co-workers20c allowed
isolation of stereochemically pure (E)-ꢀ-iodostyrene in 90%
yield. Thus, by sequencing the highly (E)-selective silylative
coupling of styrene with a stereospecific iododesilylation,
the stereochemical fidelity of the product is preserved. After
several attempts, we found that iododesilylation of (E)-
styrylsilane occurs efficiently also when the 4:1 mixture of
acetonitrile and toluene is employed as the solvent without
affecting either the reaction yield or the stereoselectivity.
Additionally, we have managed to decrease the necessary
amount of the iodinating agent to 1.2 equiv, making the
reaction more economical.
As we have previously reported, the silylative coupling
of substituted styrenes with vinylsilanes catalyzed by
ruthenium-hydride or ruthenium-silyl complexes occur-
red stereoselectively to give (E)-ꢀ-silylstyrenes in high
yields.16 Since alkyl-substituted vinylsilanes appear to be
inactive in the ruthenium-catalyzed cross-metathesis,17 the
silylative coupling offers an attractive alternative to the
selective synthesis of ꢀ-silyl-substituted vinylarenes.
(10) A recent comparison of euros/mol prices of substituted styrenes
and phenylacetylenes reveals that the former are usually two to ten times
cheaper than the latter. Styrene and 4-chlorostyrene are even 34th and 68th
of the price of their ethynyl analogues (Aldrich catalog, 2008).
(11) Morrill, Ch.; Grubbs, R. H. J. Org. Chem. 2003, 68, 6031–6034.
(12) Sashuk, V.; Samojłowicz, C.; Szadkowska, A.; Grela, K. Chem.
Commun. 2008, 2468–2470.
(13) (a) Celatka, C. A.; Panek, J. S. Tetrahedron Lett. 2002, 43, 7043–
7046. (b) Roush, W. R.; Hertel, L.; Schnaderbeck, M. J.; Yakelis, N. A.
Tetrahedron Lett. 2002, 43, 4885–4887. (c) Kim, H. J.; Pongdee, R.; Wu,
Q.; Hong, L.; Liu, H. J. Am. Chem. Soc. 2007, 129, 14582–14584.
(14) For recent reviews, see: (a) Marciniec, B. Coord. Chem. ReV. 2005,
249, 2374–2390. (b) Marciniec, B. Acc. Chem. Res. 2007, 40, 943–952.
(15) (a) Prukała, W.; Majchrzak, M.; Pietraszuk, C.; Marciniec, B. J.
Mol. Catal.: A. Chem. 2006, 254, 58–63. (b) Marciniec, B.; Majchrzak,
M.; Prukala, W.; Kubicki, M.; Chadyniak, D. J. Org. Chem. 2005, 70, 8550–
8555. (c) Prukala, W.; Marciniec, B.; Majchrzak, M.; Kubicki, M.
Tetrahedron 2007, 63, 1107–1115.
This result prompted us to attempt the iododesilylation
step in one pot with silylative coupling without further
purification of the (E)-styryltrimethylsilane intermediate. In
(17) (a) Pietraszuk, C.; Marciniec, B.; Fischer, H. Organometallics 2000,
19, 913–917. (b) Pietraszuk, C.; Fischer, H. Chem. Commun. 2000, 2463–
2464.
(16) (a) Marciniec, B.; Pietraszuk, C. Organometallics 1997, 16, 4320–
4326. (b) Itami, Y.; Marciniec, B.; Majchrzak, M.; Kubicki, M. Organo-
metallics 2003, 22, 1835–1842. (c) Marciniec, B.; Pietraszuk, C.; Jankowska,
M. Pol. Pat. 2002, P-355–875.
(18) For a review, see: Fleming, I.; Barbero, A.; Walter, D. Chem. ReV.
1997, 97, 2063–2192.
(19) (a) Eisch, J. J.; Foxton, M. W. J. Org. Chem. 1971, 36, 3520–
3526. (b) Brook, M. A.; Neuy, A. J. Org. Chem. 1990, 55, 3609–3616
.
Org. Lett., Vol. 11, No. 15, 2009
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a typical procedure, the styrene, trimethylvinylsilane (1:1
ratio), and RuHCl(CO)(PPh3)3 catalyst (1 mol %) were
dissolved in toluene (0.5 M concentration) and heated in
Schlenk bomb flask fitted with a plug valve at 100 °C for
6 h. Next, after the reaction was cooled to room temperature,
a 4-fold excess of acetonitrile and 1.2 equiv of solid
N-iodosuccinimide were added. Treatement of the silylative
coupling product with NIS caused iododesilylation in a
stereospecific manner, giving (E)-ꢀ-iodostyrene in high
geometrical purity (99%) within 1 h. The reaction was
quenched with aqueous Na2S2O3, extracted with hexane, and
concentrated to dryness. Column chromathography of the
resulting product (silica gel, eluent: hexane/ethyl acetate
50:2) afforded pure (E)-ꢀ-iodostyrene 1a in 95% overall yield
(entry 1 in Table 1). Both reactions are not air-sensitive and
coupling of trimethylvinylsilane (which could form diiodi-
nated side products), all the silylative coupling reactions were
performed with a 1:1 ratio of substrates. Moreover, the
silylative coupling reactions were carried out in 0.5 M
solution of toluene to minimize polymerization of styrenes.
Under these conditions, substituted styrenes bearing func-
tional groups such as -Me, -Ph, -OMe, -Cl, -Br, and
-F reacted successfully to give the corresponding (E)-ꢀ-
aryl vinyl iodides in high yields, irrespective of the sub-
stituent electronic character and position on the aromatic ring
(Table 1). However, the silylative coupling of 3,5-dimeth-
ylstyrene and 4-vinylbiphenyl with vinyltrimethylsilane
(Table 1, entry 4 and 10) required a longer time (10 h).
The stereoselectivity of the overall transformation is
excellent. In all cases, the (E)-double bond geometry was
strongly favored, with an approximately 99:1 E/Z ratio as
1
measured by H NMR. Moreover, the (E)-configuration of
the double bond of the compounds 1h, 1i, and 1j was further
Table 1. Synthesis of (E)-ꢀ-Aryl Vinyl Iodidesd
confirmed by single-crystal X-ray diffraction analysis.21
Next, we successfully applied our one-pot strategy to the
synthesis of selected (E)-ꢀ-aryl vinyl bromides using the
RuHCl(CO)(PPh3)3-catalyzed silylative coupling/N-bromo-
succinimide-mediated bromo-desilylation sequence. Exten-
sion to form (E)-ꢀ-aryl vinyl bromides via the succesive
silylative coupling-bromodesilylation required no further
modification to be successful. As with the aryl vinyl iodides,
the use of a solvent mixture (1:5 toluene/acetonitrile) in the
bromodesilylation step was a key to perform reaction
sequence in one pot (Schlenk bomb flask fitted with a plug
valve). Thus, a toluene solution of the selected silylative
coupling products ((E)-styryltrimethylsilanes) was treated
with a small excess of N-bromosuccinimide (NBS, 1.2 equiv)
in acetonitrile (5-fold excess with respect to the toluene) at
room temperature for 1 h to give the respective (E)-ꢀ-aryl
vinyl bromides without loss of geometrical purity (Table 2).
Table 2. Synthesis of (E)-ꢀ-Aryl Vinyl Bromidesc
a Yield of isolated products. b silylative coupling performed for 10 h.
c
E/Z ratio determined by H NMR. d Reactions were performed on a 5.0
1
mmol scale.
can be performed with commercially available reagents and
solvents without further purification.
Given our optimized conditions, we investigated the scope
of this one-pot reaction sequence using various substituted
styrenes and 4-vinylbiphenyl (Table 1). Since the synthetic
procedure requires the absence of byproducts of the homo-
a Yield of isolated products. b E/Z ratio determined by 1H NMR.
c Reactions were performed on a 5.0 mmol scale.
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Org. Lett., Vol. 11, No. 15, 2009

Using this procedure, representative (E)-ꢀ-aryl vinyl
bromides (2a-d) were prepared from styrenes containing
both electron-donating and electron-withdrawing groups in
over 98% (E)-selectivity and high yield (Table 2). It is worth
noting that, contrary to the previously reported conditions,20b
only a small excess of NBS is essential for effective
bromodesilylation of ꢀ-silylstyrenes.
In summary, we have devised a versatile, one-pot protocol
for stereoselective preparation of (E)-ꢀ-aryl vinyl iodides and
(E)-ꢀ-aryl vinyl bromides from easily accessible styrenes via
a highly selective catalytic silylative coupling/halodesilylation
sequence. For both the vinyl iodides and bromides we were
able to demonstrate functional group tolerance. Since the
presented method avoids the use of large quantities of
harmful metals or highly reactive organometallic compounds
it provides an attractive alternative to the traditional synthetic
routes employing alkynes or aldehydes as starting materials.
Acknowledgment. Financial support from the Ministry
of Science and Higher Education (Poland); Grant No. NN
204 238734 is gratefully acknowledged.
Supporting Information Available: Experimental pro-
cedures, NMR spectra, and compound characterization data
as well as X-ray analysis details. This material is available
free of charge via the Internet at http://pubs.acs.org.
(20) (a) Tamao, K.; Akita, M.; Maeda, K.; Kumada, M. J. Org. Chem.
1987, 52, 1100–1106. (b) Nagao, M.; Asano, K.; Umeda, K.; Katayama,
H.; Ozawa, F. J. Org. Chem. 2005, 70, 10511–10514. (c) Stamos, D. P.;
Taylor, A. G.; Kishi, Y. Tetrahedron Lett. 1996, 37, 8647–8650.
(21) For details, see the Supporting Information.
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