[583-55-1]  · C6H4BrI  · 2-Bromoiodobenzene  · (MW 282.91)

(starting material for coupling reactions; useful benzyne precursor)

Physical Data: mp 9-10 °C; bp 257 °C/754 mmHg; 120-121 °C/15 mmHg; d 2.257 g cm-3; n20D 1.6618.

Solubility: sol acetone.

Form Supplied in: liquid; widely available, sometimes stabilized with copper.

Coupling Reactions.

2-Bromoiodobenzene selectively couples with arenes,1 alkenes,1 and alkynes2 to afford ortho-substituted bromobenzenes in which the bromine atom can be used for further synthetic manipulation.

Suzuki Coupling.3

2-Bromoiodobenzene has been coupled with phenylboronic acids to afford biaryls using Tetrakis(triphenylphosphine)palladium(0) as catalyst (eq 1).4

Castro Coupling.5

Coupling of 2-bromoiodobenzene with Phenylethynylcopper(I) yields a (phenylalkynyl)arene (eq 2).6

Heck Reaction.7

Palladium(II) Acetate-catalyzed coupling of 2-bromoiodobenzene with Acrylic Acid leads to 2-bromocinnamic acid (eq 3).8

Coupling with vinylzinc derivatives has also been reported.9

Coupling with allylsilanes often presents problems as a result of a lack of regioselectivity. However, a regioselective palladium-catalyzed coupling with allyltrifluorosilanes has been achieved (eq 4).10

Eq 5 shows the synthetic potential of this reaction.11 Coupling of 2-bromoiodobenzene with Trimethylsilylacetylene, followed by lithium-bromine exchange with n-Butyllithium, reaction with the monoacetal of p-quinone, desilylation, and treatment with base, afforded a spirovinyl ether.

The different selectivities of the two halogens allows stepwise selective coupling. An application to the synthesis of angular phenylenes has recently been developed (eq 6).12

The same strategy has been used for the synthesis of a leukotriene analog (eq 7).13

Generation of Benzyne.14

Treatment of 2-bromoiodobenzene with metallic Lithium in ether affords benzyne (eq 8),15 which in the absence of a trapping agent trimerizes to triphenylene.15

Benzyne can also be generated by treatment of 2-bromoiodobenzene with a Grignard reagent. Nucleophilic addition of a second equiv of the Grignard reagent to benzyne affords an arylmagnesium bromide which can be reacted with an allyl halide (eq 9).16

1. Knight, D. W. COS 1991, 3, 481.
2. Sonogashira, K. COS 1991, 3, 521.
3. Miyauram, N.; Yanagi, T.; Suzuki, A. SC 1981, 11, 513.
4. Watanabe, T.; Miyaura, N.; Suzuki, A. SL 1992, 207.
5. Stephens, R. D.; Castro, C. E. JOC 1963, 28, 3313.
6. Clive, D. L. J.; Cole, D. C. JCS(P1) 1991, 3263.
7. Heck, R. F. OR 1982, 27, 345.
8. Plevyak, J. E.; Heck, R. F. JOC 1979, 44, 4078.
9. Heinze, P. L.; Burton, D. J. JFC 1986, 31, 115.
10. Hatanaka, Y.; Ebina, Y.; Hiyama, T. JACS 1991, 113, 7075.
11. Swenton, J. S.; Callinan, A.; Wang, S. JOC 1992, 57, 78.
12. Schmidt-Radde, R. H.; Vollhardt, K. P. C. JACS 1992, 114, 9713.
13. Djuric, S. W.; Haack, R. A.; Yu, S. S. JCS(P1) 1989, 2133.
14. Hoffmann, R. W. Dehydrobenzene and Cycloalkynes; Academic: New York, 1967.
15. Wittig, G. OSC 1973, 5, 1120.
16. Hart, H.; Saednya, A. SC 1988, 18, 1749.

Luis Castedo & Enrique Guitián

CSIC and University of Santiago de Compostela, Spain

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.