Chemoselective bromodeboronation of organotrifluoroborates using tetrabutylammonium tribromide: Application in (Z)-dibromoalkene syntheses

Article abstract of DOI:10.1021/ol9027144

(Chemical Equation Presented) Tetrabutylammonlum trlbromlde (TBATB) has been found to be a unique bromodeboronatlon reagent for organotrlf luoroborates. When compared to previously reported bromodeboronatlon methods, the mild and metal-free reaction conditions tolerate a wider range of functional groups. High reglo- and chemoselectlvlty are observed In the presence of both unsaturated carbon-carbon bonds and aldehyde functional groups. An efficient synthetic route to (Z)-dlbromoalkenes from terminal alkynes has been developed using the TBATB-medlated bromodeboronatlon as a key step.

Full text of DOI:10.1021/ol9027144

ORGANIC
LETTERS
2010
Vol. 12, No. 4
700-703
Chemoselective Bromodeboronation of
Organotrifluoroborates Using
Tetrabutylammonium Tribromide:
Application in (Z)-Dibromoalkene
Syntheses
Min-Liang Yao,† Marepally Srinivasa Reddy,† Li Yong,† Ingrid Walfish,‡ David
W. Blevins,† and George W. Kabalka*,†
Departments of Chemistry and Radiology, The UniVersity of Tennessee, KnoxVille,
Tennessee 37996-1600, and Department of Chemistry, State UniVersity of New York at
New Paltz, New York 12561
kabalka@utk.edu
Received November 24, 2009
ABSTRACT
Tetrabutylammonium tribromide (TBATB) has been found to be a unique bromodeboronation reagent for organotrifluoroborates. When compared
to previously reported bromodeboronation methods, the mild and metal-free reaction conditions tolerate a wider range of functional groups.
High regio- and chemoselectivity are observed in the presence of both unsaturated carbon-carbon bonds and aldehyde functional groups.
An efficient synthetic route to (Z)-dibromoalkenes from terminal alkynes has been developed using the TBATB-mediated bromodeboronation
as a key step.
Aryl halides are important synthetic intermediates that are
used extensively in carbon-carbon and carbon-heteroatom
bond-forming reactions.1 The most common method for
preparing aryl halides is the electrophilic halogenation of
arenes, but the regiochemistry of this process is determined
by the electronic nature of the arene’s substituents. As a
consequence, until recently,2 multistep syntheses have been
required to obtain isomers that are not predicted by theory.
Furthermore, in some cases, the electrophilic reactions
generate mixtures of mono- and dihalogenated products that
are difficult to separate.3 To overcome these limitations,
alternative halogenation methods have been developed that
include the conversion of anilines to aryl halides Via
diazonium salts (Sandmeyer reaction)4 and the halodemeta-
lation of organometallic species (Zn,5 Li,6 Sn,7 Hg,8 Si,9 B,10
etc.).
(3) (a) Choi, H. Y.; Srisook, E.; Jang, K. S.; Chi, D. Y. J. Org. Chem.
2005, 70, 1222. (b) Hermann, G. J.; Annis, M. C.; Edwards, P. D.; Corrales,
M.; D´ıaz, L.; Goodnow, R. A. Synthesis 2008, 221.
(4) Hodgson, H. H. Chem. ReV. 1947, 40, 251.
(5) (a) Menzel, K.; Fisher, E. L.; DiMichele, L.; Franta, F.; Nelson,
T. D.; Kress, M. H. J. Org. Chem. 2006, 71, 2188. (b) Seggio, A.; Chevallier,
F.; Vaultier, M.; Mongin, F. J. Org. Chem. 2007, 72, 6602. (c) L’Helgoual’ch,
J.-M.; Seggio, A.; Chevallier, F.; Yonehara, M.; Jeanneau, E.; Uchiyama,
M.; Mongin, F. J. Org. Chem. 2008, 73, 177.
† The University of Tennessee.
‡ State University of New York.
(1) Metal-Catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: New York, 1997.
(6) Hartung, C. G.; Fecher, A.; Chapell, B.; Snieckus, V. Org. Lett. 2003,
5, 1899.
(2) Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593.
10.1021/ol9027144  2010 American Chemical Society
Published on Web 01/19/2010

Among the organometallic reagents investigated, orga-
noboron derivatives have drawn much attention because they
are generally nontoxic and stable under atmospheric condi-
tions. With the development of palladium-catalyzed bory-
lations of aryl triflates (as well as tosylates and halides),11
iridium-catalyzed direct borylations of arenes via C-H bond
activation,12 and the syntheses of functionalized organotri-
fluoroborates through a variety of organic transformations,13
the ready availability of numerous organoboron derivatives
enhances the significance of modern organoboron-based
chemistry. Prompted by our long-term interest in efficient
radiohalogenation reactions based on organoboron
chemistry,10a-d,14 we have developed halodeboronations of
electron-rich arylboronic esters and potassium aryltrifluo-
roborates using a chloramine-T/halide system. In collabora-
tion with Huffman, we also developed a CuBr2-mediated
bromodeboronation method10f that successfully bromode-
boronates arylboronic esters bearing both electron-donating
and electron-withdrawing groups. The method has been
successfully applied in the synthesis of meta-halogenated 1,3-
disubstituted arenes.10g The bromodeboronation of arylbo-
ronic acids using dibromodimethylhydantoin and a catalytic
amount of NaOMe in acetonitrile was also reported.10e
Although this method has been used successfully in a
scaleable synthesis of 2-bromo-3-fluorobenzonitrile, the use
of NaOMe is problematic in the synthesis of compounds
containing base-sensitive functional groups.15
In a continuation of our halogenation studies, we discov-
ered that commercially available tetrabutylammonium tri-
bromide (TBATB) is a powerful bromodeboronation reagent
for converting potassium aryltrifluoroborates to aryl bro-
mides. For example, at room temperature, a potassium
aryltrifluoroborate bearing a nitro group readily undergoes
bromodeboronation to produce the corresponding aryl bro-
mide in good yield within 40 min (Scheme 1). In contrast,
under previously reported bromodeboronation conditions
(chloramine-T/NaBr), only a trace amount of product was
formed after 24 h at reflux. To the best of our knowledge,
this is the first report of TBATB being used to convert a
carbon-metal bond to a carbon-bromine bond.
Scheme 1. Efficiency of Bromodeboration Using TBATB
Compared to That of Previous Method
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Although the interconversion between arylboronic acids,
boronic esters, and organotrifluoroborates is known,16 the
use of organotrifluoroborate precursors for bromodeborona-
tion offers several advantages over the other organoboron
derivatives. These advantages include (i) simple
preparation,13,16b (ii) straightforward purification,17 and (iii)
easy isolation of the brominated product due to the large
polarity difference between precursors and products.
The scope of the new bromination reaction is highlighted
in Table 1. As shown in Table 1, a variety of functional
groups, including methoxy, aldehyde, ester, amide, phenol,
cyano, and nitro groups, survive the new bromodeboronation
reaction. The tolerance of the aldehyde group is remarkable
since TBATB has been reported to convert aldehydes to
acids.18 As distinguished from the previously reported CuBr2-
mediated bromodeboronation, the new copper-free reaction
permits the presence of phenol and amide groups by
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J. Org. Chem. 2004, 69, 566. (f) Thompson, A. L. S.; Kabalka, G. W.;
Alkula, M. R.; Huffman, J. W. Synthesis 2005, 547. (g) Murphy, J. M.;
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Org. Lett., Vol. 12, No. 4, 2010
701

obviating undesired copper-catalyzed side reactions.19 For
an aryltrifluoroborate bearing an activated methyl group
(product 1l), no bromination of the methyl group is detected.
Generally speaking, aryltrifluoroborates bearing electron-
donating groups are converted to the corresponding bro-
moarenes in good to excellent yields at room temperature
within 20 min. Aryltrifluoroborates bearing electron-
withdrawing groups require slightly longer reaction times.
However, simply elevating the reaction temperature greatly
facilitates the reaction without inducing undesirable side
reactions.
Scheme 2
.
Bromodeboronation of Alkenyl- and
Alkynyltrifluoroborates
Table 1. Conversion of Potassium Aryl Trifluoroborates to Aryl
Bromidesa
It has also been reported that the alkenyl group in enones
undergoes bromination at a higher rate than a simple alkene
using TBATB.21 However, aryltrifluoroborate 4 was found
to be chemoselectively bromodeboronated to give 5 in 61%
yield (Scheme 3).
Scheme 3
.
Chemoselectively Bromodeboronation in the
Presence of Enone
We were also able to brominate allyltrifluoroborate 6, a
trifluoroborate whose precursor allylboronic ester has been
found to be unstable (Scheme 4).17b Unfortunately, the
reaction gives a mixture of allyl bromide products (7:8 )
∼3:2). Attempts to bromodeboronate alkyltrifluoroborates
using TBATB were unsuccessful.
a Reaction carried at room temperature for 20 min unless otherwise
noted. b Isolated yield. c Reaction runs for 40 min. d Reaction runs at 60
°C for 2 h. e GC yield. f Reaction runs at room temperature for 12 h.
The bromodeboronation of alkenyl- and alkynyltrifluo-
roborates was also examined (Scheme 2). These reactions
proceed smoothly at room temperature to produce alkenyl
and alkynyl bromides, respectively, in good to excellent
yields. The retention of stereochemistry of the alkenyl group
is attractive because stereoselective halodemetalation of the
corresponding vinylsilanes can be challenging.20 Chemose-
lective bromodeboronation in the presence of unsaturated
carbon-carbon bonds is notable since TBATB is considered
to be an environmentally benign brominating reagent for
alkenes and alkynes.21
Scheme 4. Bromodeboronation of Allyltrifluoroborate
(19) Cu-mediated coupling of phenols and amides with aryl boronic acids
(esters): (a) Tzschucke, C. C.; Murphy, J. M.; Hartwig, J. F. Org. Lett.
2007, 9, 761. (b) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters,
M. P. Tetrahedron Lett. 1998, 39, 2933.
The synthesis of thermodynamically disfavored (Z)-
dibromoalkenes has long been a challenge in organic
(20) Ilardi, E. A.; Stivala, C. E.; Zakarian, A. Org. Lett. 2008, 10, 1727.
(21) Chaudhuri, M. K.; Khan, A. T.; Patel, B. Tetrahedron Lett. 1998,
39, 8163.
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1985, 26, 1065. (b) Mataka, S.; Liu, G.-B.; Tashiro, M. Synthesis 1995,
133. (c) Ye, C.; Shreeve, J. M. J. Org. Chem. 2004, 69, 8561.
702
Org. Lett., Vol. 12, No. 4, 2010

synthesis.22 Synthetic methods available in the literature
generally require either long reaction times or elevated
reaction temperatures. As a result of the thermal instability
of (Z)-dibromoalkene, the reported methods normally give
poor isolated yields and the products are often contaminated
by the (E)-isomer.22 Encouraged by the retention of config-
uration in the bromodeboronation of alkenyltrifluoroborates
noted earlier, we examined the feasibility of a two-step
synthetic route to (Z)-dibromoalkenes, such as 9, from
terminal alkynes (Scheme 5). Pure (Z)-isomers were isolated
in good yields from readily prepared, stereodefined (Z)-2-
bromovinyltrifluoroborates.23
mide produces a mixture of protodeboronation and bromode-
boronation products. Although previous reports25 have
demonstrated that TBATB is a substitute for both Br2 and
anhydrous HBr, it has never been considered as a potential
source of “Br+”. Notably, Br2, either commercially available
or generated in situ, has proven to be ineffective for
bromodeboronation reactions in the absence of strong
bases.10e,g Bromodeboronation reactions of boronic acids and
boronic esters using TBATB are much slower at room
temperature when compared to the potassium aryltrifluo-
roborates.
In conclusion, we have discovered that commercially
available TBATB is a powerful bromodeboronation reagent
for organotrifluoroborates. Under mild reaction conditions,
aryl, alkenyl, and alkynyl trifluoroborates bearing a wide
range of functional groups can be converted to the corre-
sponding bromo derivatives in good to excellent yields. High
regio- and chemoselectivity are observed in the presence of
unsaturated carbon-carbon bonds and aldehyde functional
groups. In addition, an efficient synthetic route to (Z)-
dibromoalkenes from terminal alkynes has been developed
using the TBATB mediated bromodeboronation as a key step.
Mechanistic studies are currently underway.
Scheme 5. Two-Step Synthetic Route to (Z)-Dibromoalkenes
At present, little is known concerning the mechanism of
the new bromination reaction. The slow bromodeboronation
of potassium 2-naphthalenyltrifluoroborate in the presence
of tetrabutylammonium bromide (which leads to water-
soluble tetrabutylammonium trifluoroborate salt) in the
presence of chloramine-T appears to rule out simple solubility
effects.24 However, it is clear that the tetrabutylammonium
counterion does influence the bromodeboronation reaction
since bromodeboronation reactions using pyridinium tribro-
Acknowledgment. Financial support from the U.S. De-
partment of Energy and the Robert H. Cole Foundation is
acknowledged. I.W. is grateful for a University of Tennessee
Summer Undergraduate Research Fellowship. We also thank
Frontier Scientific for providing organoboronic acids and
organotrifluoroborate precursors.
Supporting Information Available: Procedures for syn-
thesis and characterization of products (1H and 13C NMR
data). This material is available free of charge via the Internet
at http://pubs.acs.org.
(23) Yao, M.-L.; Reddy, M. S.; Zeng, W.; Hall, K.; Walfish, I.; Kabalka,
G. W. J. Org. Chem. 2009, 74, 1385.
(24) De, S.; Welker, M. E. Org. Lett. 2005, 7, 2481.
(25) (a) Gopinath, R.; Patel, B. K. Org. Lett. 2000, 2, 4177. (b) Figueira,
V. B. C. Synlett 2006, 1681.
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