Preparation of 2-BF3-substituted 1,3-dienes and their Diels-Alder/cross-coupling reactions

Article abstract of DOI:10.1021/ol050794s

(Chemical Equation Presented) 2-BF₃-substituted 1,3-butadienes with potassium and tetrabutylammonium counterions have been prepared in gram quantities from chloroprene via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F NMR. Diels-Alder reactions of these dienes with ethyl acrylate and methyl vinyl ketone are reported, as well as subsequent Pd-catalyzed cross-coupling reactions of those Diels-Alder adducts.

Full text of DOI:10.1021/ol050794s

ORGANIC
LETTERS
2005
Vol. 7, No. 12
2481-2484
Preparation of 2-BF3-Substituted
1,3-Dienes and Their Diels−Alder/
Cross-Coupling Reactions
Subhasis De and Mark E. Welker*
Department of Chemistry, Wake Forest UniVersity, P.O. Box 7486,
Winston-Salem, North Carolina 27109
welker@wfu.edu
Received April 12, 2005
ABSTRACT
2-BF3-substituted 1,3-butadienes with potassium and tetrabutylammonium counterions have been prepared in gram quantities from chloroprene
via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by 1H, 13C, 11B,
and 19F NMR. Diels
catalyzed cross-coupling reactions of those Diels
−
Alder reactions of these dienes with ethyl acrylate and methyl vinyl ketone are reported, as well as subsequent Pd-
−Alder adducts.
Reports of main group element substituted 1,3-dienes and
their reaction chemistry are still fairly rare in organic
chemistry. 2-Triethylsilyl-1,3-butadiene and a few of its
Diels-Alder reactions were reported by Ganem and Batt in
1978.1 Fleming and co-workers reported 1-trimethylsilyl-1,3-
butadiene in 19762 and its Diels-Alder dimerization in
1981.3 Paquette and Daniels reported some 2-silyl-substituted
1,3-cyclohexadienes in 1982 but none of their Diels-Alder
chemistry.4 Silyl-substituted diene chemistry was reviewed
in 1993.5 Although not containing a diene carbon to silicon
bond, related 2-trimethylsilyloxy-1,3-dienes have also been
transmetalated to zirconium.6 A 2-phenylseleno and 2-tri-
alkylstannyl-1,3-butadiene and their Diels-Alder reactions
were reported by Bates and co-workers in 1987.7 Much less
has been reported previously about aluminum-substituted 1,3-
dienes. Eisch8 and Hoberg9 reported the preparation of
alumina-1,3-cyclopentadienes decades ago, but very little has
been done with them synthetically.10
Most work reported with main group substituted dienes
has been done with the 1-(dialkoxyboryl)-1,3-butadienes (1),
sometimes termed 1,3-dienyl-1-boronates. These compounds
were reported by Vaultier in 1987,11 and numerous reports
of their Diels-Alder chemistry have appeared from the
laboratories of Vaultier,12-15 Lallemand,13,15-18 and others.19-21
Most of these reports use the dienylboronates in [4 +
2]/allylation tandem reactions (1-4), and this sequence is
now often called the Vaultier tandem sequence (Scheme 1).
(10) Fang, H. Y.; Zhao, C. J.; Li, G. T.; Xi, Z. F. Tetrahedron 2003, 59,
3779.
(11) Vaultier, M.; Truchet, F.; Carboni, B.; Hoffmann, R. W.; Denne, I.
Tetrahedron Lett. 1987, 28, 4169.
(12) Garnier, L.; Plunian, B.; Mortier, J.; Vaultier, M. Tetrahedron Lett.
1996, 37, 6699.
(13) Lallemand, J. Y.; Six, Y.; Ricard, L. Eur. J. Org. Chem. 2002, 503.
(14) Mazal, C.; Vaultier, M. Tetrahedron Lett. 1994, 35, 3089.
(15) Six, Y.; Lallemand, J. Y. Tetrahedron Lett. 1999, 40, 1295.
(16) Ohanessian, G.; Six, Y.; Lallemand, J. Y. Bull. Soc. Chim. Fr. 1996,
133, 1143.
(17) Renard, P. Y.; Lallemand, J. Y. Tetrahedron: Asymmetry 1996, 7,
2523.
(18) Renard, P. Y.; Lallemand, J. Y. Bull. Soc. Chim. Fr. 1996, 133,
143.
(19) Wang, X. B. J. Chem. Soc., Chem. Commun. 1991, 1515.
(20) Zhang, A.; Kan, Y.; Jiang, B. Tetrahedron 2001, 57, 2305.
(21) Gao, X. R.; Hall, D. G. Tetrahedron Lett. 2003, 44, 2231.
(1) Batt, D. G.; Ganem, B. Tetrahedron Lett. 1978, 3323.
(2) Fleming, I.; Percival, A. J. Chem. Soc., Chem. Commun. 1976, 681.
(3) Carter, M. J.; Fleming, I.; Percival, A. J. Chem. Soc., Perkin Trans.
1 1981, 2415.
(4) Daniels, R. G.; Paquette, L. A. Organometallics 1982, 1, 1449.
(5) Luh, T. Y.; Wong, K. T. Synthesis-Stuttgart 1993, 349-370.
(6) Ganchegui, B.; Bertus, P.; Szymoniak, J. Synlett 2001, 123.
(7) Bates, G. S.; Fryzuk, M. D.; Stone, C. Can. J. Chem. 1987, 65, 2612.
(8) Eisch, J. J. Kaska., W. C. J. Am. Chem. Soc. 1966, 88, 2976.
(9) Hoberg, H.; Krausegoing, R. J. Organomet. Chem. 1977, 127, C29.
10.1021/ol050794s CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/17/2005

Boron Diene Preparation. Potassium organotrifluorobo-
rates were first introduced as alternatives to boronic esters
and acids in 1995.29 Since then, many have reported on their
utility and advantages, such as atom economy compared to
boronic acids and esters, their ease of purification and
disposal, their monomeric rather than trimeric nature, and
their air stability.30 Given the reported stability and utility
of this class of compounds, we recently set out to prepare
the first 1,3-dienyl-2-trifluoroborates. We chose to prepare
the butadiene initially and used a route that involved
Scheme 1. Reactions of 1, 3-Dienyl-1-boronates
31,32
preparing the Grignard reagent of chloroprene (7),
followed by its quenching with trimethylborate (B(OMe)3)
and aqueous KHF2. This new boron-substituted dienyl (8)
is a white, air-stable solid and shows no propensity to
dimerize.33 It has now been prepared on a several-gram scale
In general, the regioselectivities and endo/exo selectivities
of the Diels-Alder reactions of these 1,3-dienyl-1-boronates
are in the 4-9:1 range. One report also exists of a Suzuki
coupling of a 1,3-dienyl-1-boronate (1).22
1
(78%), characterized by H, 13C, 11B, and 19F NMR, and
appears by NOESY to be predominantly in a solution
conformation close to s-trans (9).
In contrast to the 1,3-dienyl-1-boronates, few report the
preparation and Diels-Alder chemistry of 1,3-dienyl-2-
boronates (5).23,24 The Diels-Alder chemistry of this class
of compounds has presumably been limited by their pro-
pensity to dimerize (6) even at room temperature.25 Renaud
and co-workers have recently reported a clever enyne ring-
closing metathesis reaction involving boronate-substituted
alkynes, which leads to more highly functionalized 1,3-
dienyl-2-boronates, but many of these compounds also
proved unstable and prone to dimerization.26
We have also prepared the tetra n-butylammonium (TBA)
salt of the BF3 substituted diene (10) (85%).34 TBA salts of
other trifluoroborates have been shown to improve cross-
coupling yields considerably, presumably as a result of their
greater organic solvent solubility.35 The bulkier ammonium
salt should also increase organic solvent solubility of this
class of dienes and may drive their solution conformation
more toward s-cis and increase their Diels-Alder reactivity.
Because so much is now known about cross-coupling/
transmetalation reactions of boron-, aluminum-, and silicon-
substituted alkenyl compounds, we were convinced that when
we found a synthetic route to stable compounds in the 1,3-
dienyl-2-main group element family, then these compounds
would prove useful to synthetic organic chemists. Our
experience in transition metal dienyl complex chemistry had
also been that 2-metal-substituted 1,3-dienes were vastly
superior to 1-metal-substituted 1,3-dienes27,28 both in rate
enhancement and stereoselectivity, so we expected the same
to be true for main group susbstituted dienes if we could
develop this chemistry. Our preliminary results in this area
are outlined below.
Diels-Alder/Cross-Coupling. We have begun to explore
the tandem reaction chemistry of these dienyl trifluoroborates
(8 and 10). We first tried Diels-Alder reactions of diene
(8) with ethyl acrylate and methyl vinyl ketone (MVK) and
found that boron-containing cycloadducts (11-14) could be
isolated in high yield. Those cycloadducts (11-14) could
then subsequently be cross-coupled using Pd catalysis to yield
organic cycloadducts (15, 16) (Scheme 2).
We then performed a series of tandem Diels-Alder/cross-
coupling reactions without isolating and characterizing boron
intermediates as shown in Table 1. We first heated the boron
diene (8 or 10) and dienophile then added Pd(OAc)2 (0.5
(22) Tivola, P. B.; Deagostino, A.; Prandi, C.; Venturello, P. Org. Lett.
2002, 4, 1275.
(23) (a) Brown, H. C.; Bhat, N. G.; Iyer, R. R. Tetrahedron Lett. 1991,
32, 3655. (b) Guennouni, N.; Rasset-Deloge, C.; Carboni, B.; Vaultier, M.
Synlett 1992, 581.
(24) Kamabuchi, A.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1993,
34, 4827.
(25) Carreaux, F.; Posseme, F.; Carboni, B.; Arrieta, A.; Lecea, B.;
Cossio, F. P. J. Org. Chem. 2002, 67, 9153.
(26) Renaud, J.; Graf, C. D.; Oberer, L. Angew. Chem., Int. Ed. 2000,
39, 3101.
(27) Hayes, B. L.; Adams, T. A.; Pickin, K. A.; Day, C. S.; Welker, M.
E. Organometallics 2000, 19, 2730.
(29) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M.
R. J. Org. Chem. 1995, 60, 3020.
(30) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
(31) Nunomoto, S.; Yamashita, Y. J. Org. Chem. 1979, 44, 4788.
(32) Fleming, F. F.; Jiang, T. J. Org. Chem. 1997, 62, 7890.
(33) Molander, G. A.; Dehmel, F. J. Am. Chem. Soc. 2004, 126, 10313.
(34) Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099.
(35) Thadani, A. N.; Batey, R. A. Tetrahedron Lett. 2003, 44, 8051.
(28) Hayes, B. L. Ph. D. Dissertation, Wake Forest, 2000.
2482
Org. Lett., Vol. 7, No. 12, 2005

Table 1. Tandem Diels-Alder/Cross-Coupling Reactions of Boron Dienesa
a Notes: (/) reactions run in a microwave; (#) 1.5% Pd cat used.
mol %), 3 equiv K2CO3, and refluxed in EtOH or MeOH
for 5 h. The sequence appears useful for unsubstituted phenyl
halides (entries 3 and 8), phenyl halides substituted by
electron-donating (entries 4, 7, and 9) or -withdrawing groups
(entries 1, 2, 6, 12, and 13), and heteroaromatic halides
(entries 5, 10, and 11). The yields for this tandem sequence
are generally slightly higher for acrylate rather than MVK
adducts (entries 1-7 versus 8-13). Phenyl halides with
electron-withdrawing groups (entries 1, 2, 6, 12, and 13)
typically produce products in 5-10% higher isolated yield
than those with electron-donating groups (entries 4, 7, and
9). The preference for the para over meta regioisomer in these
initial experiments ranges from 3 to 5:1. We wondered if
the tetrabutylammonium counterion might have some effect
on isolated yields (due to increased solubility) or regio-
chemical outcomes (due to steric effects), but comparison
of entries 4 and 7 indicates dienes 8 and 11 are almost
identical in product outcome. Performing these reactions in
a commercial microwave reactor drastically reduces the time
required and produces a product in almost identical yield
and regiochemistry to the one obtained from a classical
thermal reaction (entries 1 and 2 and 10 and 11) Even in its
limited form, Table 1 demonstrates that 8 or 11 can serve as
a synthon for a host of 2-substituted-1,3-butadienes. We have
not worried about regiochemistry here in these early studies,
since we ultimately plan to transmetalate boron dienes to
Rh prior to cycloadditions and we have already demonstrated
that low valent transition-metal-substituted dienes participate
in Diels-Alder reactions with excellent regio- and stereo-
selectivity.36
Scheme 2. Sequential Diels-Alder/Cross-Coupling
In summary, we have prepared new, stable, monomeric
dienyl trifluoroborates in high yield and find that they readily
participate in Diels-Alder/cross-coupling tandem reactions.
We will report the transition-metal-catalyzed reaction chem-
istry of these main group element substituted dienes in due
course.
(36) Welker, M. E. Curr. Org. Chem. 2001, 5, 785.
Org. Lett., Vol. 7, No. 12, 2005
2483

Acknowledgment. We thank the National Science Foun-
dation for their support of this work (CHE-0104083 and
0450722) and the NMR instrumentation used to characterize
the compounds reported here. The Duke University Center
for Mass Spectrometry performed high resolution mass
spectral analyses. The authors would like to thank Dr. Marcus
W. Wright for NMR assistance.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL050794S
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Org. Lett., Vol. 7, No. 12, 2005