Structure-dependent oxidative bromination of unsaturated C-C bonds mediated by selectfluor

Article abstract of DOI:10.1021/jo048383x

A number of olefins were subjected to oxidative bromination using Selectfluor/KBr. For different types of substrates, addition, monobromine-substituted, or Hunsdiecker-Borodin reaction products can be readily afforded.

Full text of DOI:10.1021/jo048383x

SCHEME 1. Proposed Mechanism for Selectfluor
with Bromide
Structure-Dependent Oxidative
Bromination of Unsaturated C-C Bonds
Mediated by Selectfluor
Chengfeng Ye and Jean’ne M. Shreeve*
Department of Chemistry, University of Idaho,
Moscow, Idaho 83844-2343
TABLE 1. Oxidative Halogenation of Olefinsa
jshreeve@uidaho.edu
Received September 14, 2004
yield (%)
Abstract: A number of olefins were subjected to oxidative
bromination using Selectfluor/KBr. For different types of
substrates, addition, monobromine-substituted, or Huns-
diecker-Borodin reaction products can be readily afforded.
no.
substrate
styrene
R-Me-styrene
trans-stilbene
styrene
sol
3
4
1
2
3
4
5
6
A
A
A
B
B
B
98 (3a)
99 (3b)
93 (3c)
66 (3d)
79 (3e)
89 (3f)
30 (4d)b
13 (4e)b,c
8 (4f)
R-Me-styrene
trans-stilbene
Since its discovery in 1980, 1-chloromethyl-4-fluoro-
1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Se-
lectfluor, F-TEDA-BF4) (1) has been the subject of
considerable interest as a powerful and user-friendly
(nongaseous, nonexplosive, less-toxic) site-selective, elec-
trophilic fluorinating agent.1 In the presence of Select-
fluor, some additional halogenation reactions were also
performed;2 e.g., iodine was introduced at the most
electron-rich and the least sterically hindered position
on the substituted benzene ring2a,b and reactions of aryl
alkyl ketones in methanol solutions of iodine resulted in
the formation of the corresponding R-iodoketones in good
yields.2c-e Recently, 1 also was used to generate useful
electrophiles, such as Cl+, Br+, SCN+, and NO2+, from
their respective sodium and potassium salts in acetoni-
trile (Scheme 1), which were reacted subsequently in situ
with a variety of aromatic substrates.3
a Conditions: olefin (1 mmol), KBr (2.5 mmol), and Selectfluor
(2 mmol), solvent: CH3CN (25 mL), and methanol (A) or water
(B) (1 mL); for solvent A, R3 ) CH3, for B, R3 ) H; reaction time
30 min. b GC-MS result. c Plus 8% addition-elimination product.
other systems such as DMP/TBAB8 and NaIO4/NaX9 also
give interesting results.
In this paper, we describe mild and structure-depend-
ent brominations of olefins using Selectfluor/KBr. More
than a decade ago, Lal reported that, in the presence of
the weak nucleophiles H2O, AcOH, or MeOH in CH3CN,
Selectfluor reacts with styrene derivatives or trans-
stilbene to introduce a fluorine atom and the nucleophile
component on the adjacent carbon atom.10 Similarly, in
our work, when styrene derivatives were treated with
Selectfluor/KBr, the bromomethoxylation addition prod-
ucts (entries 1-3, Table 1) were readily obtained in high
yields when methanol was used as the counter nucleo-
phile.11 When water was used as the counter nucleophile
under the same conditions, more complex, dibrominated
compounds were detected in addition to the expected
bromohydrins. For R-methyl styrene, a small quantity
of addition-elimination products were also formed which
may have resulted from the corresponding dibromide (4e)
by elimination in the presence of base (2) which is the
reduction product of Selectfluor (Scheme 1).9 The forma-
tion of the trans product of trans-stilbene indicates it
undergoes a bromonium intermediate (Table 1). However,
chloride is less reactive than bromide, i.e., when NaCl
was used with R-methyl styrene, a mixture of fluorinated
and chlorinated products was obtained in a ratio of 3:1.
At the present time, oxidative halogenation continues
to be of great interest because it precludes the use of
gaseous or volatile halogens. A number of protocols are
available to achieve bromination of alkenes and alkynes
using Br- instead of Br2. The most commonly used
4
oxidant is 30% H2O2 with concomitantly poor stereo-
selectivity and unwanted side products. Other widely
used oxidants for this purpose include cerium(IV) am-
monium nitrate (CAN),5 HNO3,6 and oxone,7etc. Some
(1) (a) Banks, R. E. J. Fluorine Chem. 1998, 87, 1. (b) Singh, R.;
Shreeve, J. M. Acc. Chem. Res. 2004, 37, 31.
(2) (a) Zupan, M.; Iskra, J.; Stavber, S. Tetrahedron Lett. 1997, 38,
6305. (b) Stavber, S.; Kralj, P.; Zupan, M. Synlett 2002, 598. (c) Stavber,
S.; Kralj, P.; Zupan, M. Synthesis 2002, 1513. (d) Stavber, S.; Jereb,
M.; Zupan, M. Chem. Commun. 2002, 488. (e) Stavber, S.; Kralj, P.;
Zupan, M. Synlett 2002, 598.
(3) Syvret, R. G.; Butt, K. M.; Nguyen, T. P.; Bulleck, V. L.; Rieth,
R. D. J. Org. Chem. 2002, 67, 4487.
(4) (a) Cervinka, O.; Dudek, V.; Fabryova, A.; Kolar, J.; Lukac, J.;
Simon, J.; Viktorin, M. Collect. Czech. Chem Commun. 1989, 54, 2748.
(b) Mukhopadhyay, S.; Ananthakrishnan, S.; Chandalia, S. B. Org.
Process Res. Dev. 1999, 3, 451. (c) Dakka, J.; Sasson, Y. J. Chem. Soc.,
Chem. Commun. 1987, 1421. (d) Mukhopadhyay, S.; Mukhopadhyaya,
J. K.; Ponde, D. E.; Cohen, S.; Kurkalli, B. Org. Process Res. Dev. 2000,
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(7) (a) Dieter, R. K.; Nice, L. E.; Velu, S. E.; Tetrahedron Lett. 1996,
37, 2377. (b) Butler, A.; Walker, J. V. Chem. Rev. 1993, 93, 1937. (c)
Martinez-Perez, J. A.; Pickel, M. A.; Caroff, E.; Woggon, W.-D. Synlett
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(8) Ramanarayanan, G. V.; Shukla, V. G.; Akamanchi, K. G. Synlett
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(10) Lal, G. S. J. Org. Chem. 1993, 58, 2791.
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(b) Weissmuller, J.; Kraemer, W.; Berg, D.; Reinecke, P.; Brandes, W.;
Haenssler, G.; Lerssen, K. US Patent 4,615,725, 1985.
(5) Nair, V.; Panicker, S. B.; Augustine, A.; George, T. G.; Thomas
S.; Vairamani M. Tetrahedron 2001, 57, 7417.
(6) Joshi, A. V.; Baidossi M.; Mukhopadhyay, S.; Sasson Y. Org.
Process Res. Dev. 2004, 8, 568.
10.1021/jo048383x CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/04/2004
J. Org. Chem. 2004, 69, 8561-8563
8561

TABLE 3. Oxidative Bromination of Conjugated Olefins
SCHEME 2. Selectfluor-Mediated Brominating
Ring-Closure Reactions
with a Phenyl Group at â-Positiona
SCHEME 3. Oxidative Bromination of
Phenylacetylenea,b
a Conditions: olefin (1 mmol), KBr (2.5 mmol), and Selectfluor
(2 mmol), solvent CH3CN/H2O ) 25:1 (v/v); reaction time 30 min.
bIsolated yields.
TABLE 2. Oxidative Bromination of Conjugated
Olefinsa
a Conditions: olefin (1 mmol), KBr (2.5 mmol), and Selectfluor
(2 mmol), solvent CH3CN/H2O ) 25:1 (v/v); reaction time 2 h except
entry 6 needed 20 h. b Isolated yields.
likely that the byproduct of Selectfluor, compound 2,
plays an important role as base to trigger the elimination
reaction in our case. Also, noteworthy for 2-cyclopent-
enone, when CH3CN/methanol was used as solvent, an
unidentified volatile product was formed. Because of its
low boiling point, it was difficult to separate from
acetonitrile, and only when CH3CN/H2O was used as
solvent was it possible to obtain 2-bromo-2-cyclopenten-
1-one.
a Conditions: olefin (1 mmol), KBr (2.5 mmol), and Selectfluor
(2 mmol), solvent CH3CN/H2O ) 25:1 (v/v); reaction time 2 h.
b Isolated yields.
However, the current method described here is very
sensitive to the structure of the substrate. When a
conjugated carbonyl with a phenyl group at the â-position
was subjected to oxidative bromination under the same
conditions, only erythro-dibromination products were
obtained when either CH3CN/methanol or CH3CN/H2O
was used as solvent. For the conjugated alkyne (entry 4,
Table 3) only the dibrominated alkene, and not the R,R-
dibromo carbonyl compound, was found. For the sub-
strate containing both a conjugated double bond and an
allyl or propargyl group, tetrabrominated products were
observed, and no ring-closure product was detected.
Interestingly, for trans,trans-1,4-diphenyl-1,3-butadiene
(Table 3, entry 7), a nonbrominated rearrangement
product was observed along with other unidentified
species.
Intramolecular ring-closure reactions also proceeded
smoothly with heating but lacked diastereoselectivity
(Scheme 2).
Interestingly, treatment of phenylacetylene with Se-
lectfluor/KBr/H2O gave R,R-dibromoacetophenone not
R-bromoacetophenone, similar to the difluorinated prod-
uct obtained with Selectfluor in CH3CN/H2O.10 Moreover,
when a small amount of acid or base was added, the
products were entirely different. When Na2CO3 was
added to the reaction system followed by Selectfluor, the
sole product was trans-1, 2-dibromostyrene, while using
acetic acid led to the formation of cis-1,2-dibromostyrene
as the major product (Scheme 3).
For a system having a double bond conjugated with a
carbonyl group, R-bromo-conjugated products were ob-
tained in good yields (Table 2). Such compounds are
normally synthesized by a two-step procedure, i.e., di-
bromination followed by elimination in the presence of
base.12 Few one-pot syntheses have been reported directly
involving oxidative bromination of corresponding conju-
gated carbonyl compounds except DMP/TBAB.8,9 It is
It is supposed that owing to the electronic and bulky
effects of the phenyl group on the dibrominated inter-
(12) (a) Adav, V. K.; Senthil, G.; Babu, K. G.; Parvez, M.; Reid, J. J.
Org. Chem. 2002, 67, 1109. (b) Bose, G.; Barua, P.; Chaudhuri, M. K.;
Kalita, D.; Khan, A. T. Chem. Lett. 2001, 290.
8562 J. Org. Chem., Vol. 69, No. 24, 2004

SCHEME 4. Oxidative Bromination of Chalcone
SCHEME 5. Proposed Hunsdiecker Mechanism
Involved with Selectfluor
TABLE 4. Oxidative Decarboxylic Bromination
Reactiona
no.
R
product
E/Z
yieldb (%)
In conclusion, because of involvement of the reduced
product of Selectfluor (compound 2), the protocol of
Selectfluor/KBr behaves very differently from other
oxidative brominating systems causing it to be a sub-
strate structure-dependent brominating system.
1
2
3
H
23
24
25
95:5
97:3
>99:1
84
86
82
3-Cl
4-OH
a Conditions: olefin (1 mmol), KBr (2.5 mmol), and Selectfluor
(2 mmol), solvent CH3CN/H2O ) 25:1 (v/v); reaction time 5 h.
b Isolated yields for (E) isomer.
Experimental Section
General Methods. All of the reagents used were analytical
reagents purchased from commercial sources and used as
received. 1H, 19F, and 13C NMR spectra were recorded on a
spectrometer operating at 300, 282, and 75 MHz, respectively,
in CDCl3 unless otherwise stated. Chemical shifts are reported
in ppm relative to the appropriate standard, CFCl3 for 19F, and
mediate, a stronger base like Et3N or K2CO3 was needed
to initiate the elimination reaction13 since 2 is not strong
enough to trigger the reaction. This may explain why the
olefins described in Tables 2 and 3 behave differently.
Additionally, we found that, when chalcone was treated
with Selectfluor in dry acetonitrile without use of metha-
nol or water as a counter nucleophile, a bromoamidation
product was isolated in 67% yield (Scheme 4). Direct
fluoroamidation of active double bonds is not surprising;14
however, there are only rare reports of the direct bro-
moamidation of olefins.15 Unfortunately, efforts to extend
this reaction mode to other substrates were unsuccessful.
In such cases, bromoamidation products do form, but in
low yields and concomitantly with other very complex
products.
The products obtained with conjugated carboxylic acids
were totally different from the above systems; a Huns-
diecker-Borodin reaction-decarboxylic bromination re-
action took place accompanied by the formation of a small
amount of the cis isomers (Table 4). The ratio of trans/
cis isomers was greatly affected by the solvent used. For
trans-cinnamic acid, when the solvent was changed from
CH3CN/methanol (25:1) to CH3CN/H2O (25:1), the cor-
responding ratio increased from 4.5:1 to 95:5. Classical
Hunsdiecker-Borodin reactions usually involve use of
elemental bromine and salts of Hg(II), Tl(I), Pb(IV), Ag-
(I). Although some improved procedures are available
using Br+, stemming from NBS or KBr/H2O2, a specific
catalyst is required, such as lithium acetate, tetrabutyl-
ammonium trifluoroacetate, or triethylamine.16 This
paper is the first report of a Hunsdiecker-Borodin
reaction using Br+ without a catalyst; compound 2 is
considered to be an effective catalyst for this kind of
reaction (Scheme 5).
1
TMS for H and 13C NMR spectra.
General Procedure. To a stirred mixture of olefin (1.0 mmol)
and KBr (2.5 mmol), CH3CN (25 mL), methanol or water (1 mL),
and Selectfluor (2.0 mmol) were added. The reaction was
monitored by TLC. After completion of the reaction, the mixture
was diluted with water and extracted with CH2Cl2 (25 mL × 3).
The organic layers were combined and washed with dilute
solutions of NaHCO3, Na2SO3, and brine. It was dried over
anhydrous Na2SO4 and concentrated under reduced pressure to
give crude products, which were purified by column chromatog-
raphy packed with silica gel to afford the pure products.
2′,3′-Dibromopropyl trans-2,3-dibromo-3-phenylpropa-
noate (18): mp 53 °C, two isomers; 1H NMR δ 3.83 (dd, 1H,
J ) 10.8, 8.6 Hz), 3.90 (dd, 1H, J ) 10.8, 4.9 Hz), 4.41-4.47 (m,
1H), 4.71 (dd, 1H, J ) 12.0, 3.4 Hz), 4.79 (dd, 1H, J ) 12.0, 5.3
Hz), 4.93 (d, 1H, J ) 11.8 Hz), 5.37 (d, 1H, J ) 11.8 Hz), 7.40-
7.46 (m, 5H); 13C NMR δ 32.9, 46.8, 47.32 (47.35), 51.2 (51.3),
67.55 (67.60), 128.9, 129.8, 130.4, 138.1, 168.1. Anal. Calcd for
C12H12Br4O2: C, 28.38; H, 2.38. Found: C, 28.68; H, 2.60.
(E)-2′,3′-Dibromoallyl trans-2,3-dibromo-3-phenylpro-
panoate (19): 1H NMR δ 4.94 (d, 1H, J ) 11.8 Hz), 5.18 (s,
2H), 5.38 (d, 1H, J ) 11.8 Hz), 6.79 (s, 1H), 7.38-7.45 (m, 5H);
13C NMR δ 47.3, 51.2, 67.0, 109.5, 119.0, 129.0, 128.8, 130.4,
138.3, 168.0. Anal. Calcd for C12H10Br4O2: C, 28.49; H, 1.99.
Found: C, 28.16; H, 1.99.
Prop-2′-ynyl trans-2,3-dibromo-3-phenylpropanoate (20):
1H NMR δ 2.60 (t, 1H, J ) 2.4 Hz), 4.90 (d, 1H, J ) 11.8 Hz),
4.91 (d, 2H), 5.37 (d, 1H, J ) 11.8 Hz), 7.38-7.46 (m, 5H); 13C
NMR δ 47.2, 51.2, 54.8, 77.0, 128.9, 129.8, 130.4, 138.3, 167.9.
Anal. Calcd for C12H10Br2O2: C, 41.65; H, 2.91. Found: C, 41.55;
H, 2.92.
N-((trans-2-bromo)-3-oxo-1,3-diphenylpropyl)acet-
amide (22): mp 94-95 °C; 1H NMR δ 1.85 (s, 3H), 5.54 (d, 1H,
J ) 8.9 Hz), 6.67 (d, 1H, J ) 8.9 Hz), 7.73-7.95 (m, 10 H); 13C
NMR δ 23.7, 55.7, 76.4, 127.9, 128.7, 129.4, 129.6, 129.7, 129.8,
129.9, 134.4, 135.2, 140.6, 170.6, 200.3. Anal. Calcd for C17H16
-
BrNO2: C,58.97;H,4.66;N,4.05.Found: C,58.70;H,4.74;N,4.30.
(13) (a) Kowalski, C. J.; Weber, A. E.; Fields, K. W. J. Org. Chem.
1982, 47, 5088. (b) Marsura, A.; Cuong.; Gellon, G. Synthesis 1985,
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J. Org. Chem. 2002, 67, 6415. (b) Stavber S.; Pecan T. S.; Papez, M.;
Zupan, M. Chem. Commun. 1996, 2247. (c) Zupan, M.; Skulj, P.;
Stavber, S. Tetrahedron 2001, 57, 10027.
(15) Thakur V. V.; Talluri S. K.; Sudalai A. Org. Lett. 2003, 5, 861.
(16) (a) Das, J. P.; Roy, S. J. Org. Chem. 2002, 67, 7861. (b) Sinha,
J.; Layek, S.; Mandal, G. C.; Bhattacharjee, M. Chem. Commun. 2001,
1916. (c) Naskar, D.; Chowdhury, S.; Roy, S. Tetrahedron Lett. 1998,
39, 699.
Acknowledgment. We acknowledge the support of
the National Science Foundation (Grant No. CHE-
0315275) and AFOSR (Grant No. F49620-03-1-0209).
Supporting Information Available: Experimental pro-
cedure and characterization data for known compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO048383X
J. Org. Chem, Vol. 69, No. 24, 2004 8563