LETTER
(Diacetoxyiodo)benzene-Lithium Bromide as a Electrophilic Br+ Source
463
Table 2 Ageing Experiments in the Bromination of Anisolea
31, 2021. (c) Narender, N.; Srinivasu, P.; Ramakrishna
Prasad, M.; Kulkarni, S. J.; Raghavan, K. V. Synth.
Commun. 2002, 32, 2313. (d) Narender, N.; Srinivasu, P.;
Kulkarni, S. J.; Raghavan, K. V. Synth. Commun. 2000, 30,
3669. (e) Roche, D.; Prasad, K.; Repic, O.; Blacklock, T. J.
Tetrahedron Lett. 2000, 41, 2083.
OMe
OMe
Aged LiBr-DIB,
or aged Br2
(8) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(9) Wirth, T. Angew. Chem. Int. Ed. 2001, 40, 2812.
(10) DIB is commercially available, or can be readily prepared in
one step from iodobenzene:Hypervalent Iodine in Organic
Synthesis; Varvoglis, A., Ed.; Academic Press: , 1997, 9–10.
(11) (a) Rho, H. S.; Ko, B.-s.; Ju, Y.-s. Synth. Commun. 2001, 31,
2101. (b) Rho, H. S.; Ko, B.-s.; Kim, H. K.; Ju, Y.-s. Synth.
Commun. 2002, 32, 1303.
(12) Evans, P. A.; Nelson, J. D.; Manangan, T. Synlett 1997, 968.
(13) (a) Evans, P. A.; Brandt, T. A. Tetrahedron Lett. 1996, 37,
6443. (b) Evans, P. A.; Brandt, T. A. J. Org. Chem. 1997, 62,
5321.
Br
Time (min)
LiBr–DIB
Br2
100
100
100
95
0
5
100
98
10
30
60
97
89
56
84
(14) Kirsching, A.; Jesberger, M.; Monenschein, H. Tetrahedron
Lett. 1999, 40, 8999.
(15) Hashem, M. A.; Jung, A.; Ries, M.; Kirsching, A. Synlett
1998, 195.
a The reagents (1.1 equiv.) were aged for the appropriate time in THF
solvent, anisole was added, and the reaction quenched after 0.5 h.
(16) A Typical Procedure for DIB–LiBr Bromination: To a
solution of substrate (5 mmol) and LiBr (0.48 g, 5.5 mmol)
stirring in anhyd THF at r.t. in an open vessel DIB was added
portionwise over 5 min (1.77 g, 5.5 mmol). The suspension
was stirred for a further 25 min, water added (10 mL) and the
reaction mixture extracted with CH2Cl2 (20 mL). The
organic layer was washed with water (20 mL) and brine (20
mL), dried over MgSO4 and concentrated in vacuo, and
chromatographed (isooctane–Et2O) to give the brominated
product.
In the light of the above experiments, we propose that the
de facto electrophilic bromine source in this system is
hypervalent iodine compound 2 with an I–Br bond as pro-
posed in Scheme 1. Its mode of action may involve nu-
cleophilic attack first at iodine followed by reductive
elimination by anology with e.g., Koser’s reagent,21 or by
direct electrophilic bromine transfer with concomitant
loss of acetate and generation of iodobenzene.
In conclusion, we have developed a mild, rapid and effi-
cient method for electrophilic bromination of a wide range
of arene and alkene substrates using stoichiometric
amounts of LiBr and (diacetoxyiodo)benzene (DIB). Irre-
spective of the actual mechanism, the practical simplicity
of this method, avoiding the hazards of molecular bro-
mine, and the selectivity profile for bromolactonisation
compared to Br2 makes it attractive for synthesis.
(17) 4-Bromanisole (Table 1, entry 1): Yield: 88%; colourless
oil. 1H NMR (400 MHz, CDCl3): d = 7.36 (d, J = 9.0 Hz, 2
H, ArH), 6.76 (d, J = 9.0 Hz, 2 H, ArH), 3.76 (s, 3 H, CH3).
13C NMR (68 MHz, CDCl3): d = 158.7, 132.4, 115.8, 112.9,
55.4. MS (EI): m/z = 186, 188 [M+·]. HRMS: m/z calcd for
C7H7O79Br: 185.9680; found: 185.9697. 6-Bromo-2,3-
dihydrobenzo[1,4]dioxine (Table 1, entry 2): Yield: 74%;
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 7.00 (d, J = 2.4
Hz, 1 H, ArH), 6.91 (dd, J = 8.8, 2.4 Hz, 1 H, ArH), 6.72 (d,
J = 8.8 Hz, 1 H, ArH), 4.20 (br s, 4 H, CH2CH2). 13C NMR
(100 MHz, CDCl3): d = 144.4, 142.9, 124.3, 120.3, 118.6,
112.8, 64.3, 64.2. MS (EI): m/z = 214, 216 [M+·]. HRMS:
m/z calcd for C8H7O279Br: 213.9629; found: 213.9628. 5-
Bromobenzo[1,3]dioxole (Table 1, entry 3): Yield: 71%;
colourless oil. 1H NMR (400 MHz, CDCl3): d = 6.92 (m, 2
H, ArH), 6.66 (d, J = 8.8 Hz, 1 H, ArH), 5.95 (s, 2 H, CH2).
13C NMR (100 MHz, CDCl3): d = 148.6, 147.0, 124.3, 113.1,
112.3, 109.6, 101.7. MS (EI): m/z = 200, 202 [M+·]. HRMS:
m/z calcd for C7H5O279Br: 199.9473; found: 199.9473. 4-
Bromo-N,N-dimethylaniline (Table, entry 4): Yield: 73%;
colourless oil. 1H NMR (400 MHz, CDCl3): d = 7.27 (d, J =
8.7 Hz, 2 H, ArH), 6.55 (d, J = 8.7 Hz, 2 H, ArH), 2.89 (s, 6
H, CH3). 13C NMR (100 MHz, CDCl3): d = 149.5, 131.7,
114.1, 108.5, 40.6. MS (ES): m/z = 200, 202 [MH+]. HRMS:
m/z calcd for C8H11NBr: 200.0075; found: 200.0084. 2-
Bromo-5-methylthiophene (Table 1, entry 5): Yield: 88%;
colourless oil. 1H NMR (400 MHz, CDCl3): d = 6.83 (d, J =
3.7 Hz, 1 H, ArH), 6.51 (d, J = 3.7 Hz, 1 H, ArH), 2.42 (s, 3
H, CH3). 13C NMR (100 MHz, CDCl3): d = 141.4, 129.6,
125.5, 108.5, 15.5. MS (EI): m/z = 176, 178 [M+·]. HRMS:
m/z calcd for C5H5S79Br: 175.9295; found: 175.9336. 3-
Bromo-benzo[b]thiophene (Table 1, entry 6): Yield: 79%;
colourless oil. 1H NMR (400 MHz, CDCl3): d = 7.74–7.80
(m, 2 H, ArH), 7.40 (t, J = 7.4 Hz, 1 H, ArH), 7.35–7.32 (m,
2 H, ArH). 13C NMR (100 MHz, CDCl3): d = 138.7, 137.6,
127.6, 125.1, 123.6, 123.2, 122.8, 107.8. MS (EI): m/z = 212,
Acknowledgment
We thank the EPSRC and GlaxoSmithKline Ltd for a CASE award
(to G. C.)
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Synlett 2004, No. 3, 461–464 © Thieme Stuttgart · New York