2,3-Dibromopropene

[513-31-5]  · C3H4Br2  · 2,3-Dibromopropene  · (MW 199.87)

(a bifunctional reagent, widely employed in coupling reactions, and as a precursor of key intermediates for cycloaddition reactions)

Alternate Names: 1,2-dibromo-2-propene; 2-bromoallyl bromide.

Physical Data: bp 140-142 °C; 75-76 °C/75 mmHg; 42-43 °C/18 mmHg; d 2.045 g cm-3; n20D 1.544.

Form Supplied in: colorless oil; commercially available.

Purification: may be distilled under atmospheric pressure with very slight decomposition, but becomes highly colored on standing in a glass-stoppered bottle.

Handling, Storage, and Precautions: irritating to skin, eyes, and respiratory system. Use in a fume hood.

Introduction.

Interesting products can be prepared by taking advantage of the different reactivity of the allylic and vinylic halogen atoms. The products obtained can be further elaborated in a variety of manners, frequently leading to polycycles.

Coupling Reactions with Organometallic Reagents.

The allylic and the vinylic bromine atoms of 2,3-dibromopropene (1) can be selectively substituted in two consecutive cross-coupling steps.1 Thus 1,1-disubstituted ethylenes (2) can be easily prepared by first adding the appropriate Grignard reagent to a solution of (1) in THF at rt. After completion of the coupling reaction, a catalytic amount of NiCl2(dppp) is added, and a solution of the second Grignard reagent is added to the mixture containing the intermediate alkenyl bromide (eq 1).

The allylic bromide can be also substituted by terminal alkynes in the presence of a catalytic amount of a copper(I) salt and tetra-n-butylammonium chloride2 or by alkenylcopper reagents.3,4 Highly functionalized 2-bromo-1-alkenes are prepared5 by CuI-catalyzed reaction of functionalized organozinc halides. Alkylation (Lithium Diisopropylamide, THF/HMPA) of methyl 2-(trimethylstannyl)-1-cyclohexene-3-carboxylate with 2,3-dibromopropene affords the ester (3) which can be smoothly cyclized to compound (4) by using 2-3 equiv of Copper(I) Chloride in DMF at 60-70 °C (eq 2).6

The coupling reactions are widely utilized for the synthesis of several intermediates (e.g. 5-8) (eq 3), which are versatile reagents in cycloaddition reactions. In particular, (5) is synthesized7 in two steps: 2,3-dibromopropene is coupled with Trimethylsilylmethylmagnesium Chloride and the intermediate obtained, after transformation into a Grignard reagent, is combined with vinyl bromide in the presence of a NiII catalyst. Product (6) is formed by combining lithium (trimethylsilyl)cyanocuprate in a 3:1 THF-HMPA mixture at 0 °C with 2,3-dibromopropene.8 An alternative synthesis of (6) requires treatment of (1) with Trichlorosilane and Et3N in the presence of a catalytic amount of CuCl, and direct addition of the allyltrichlorosilane to an ether solution of Methylmagnesium Bromide.9 Diene (7) can be obtained by oxidative dimerization of the cuprate derived from (6).10 Compound (6) can be also directly transformed, by a coupling reaction, into the diene (8).11

Dienes (5) and (8) work well in consecutive Diels-Alder reactions.7,12 In particular, (5) reacts with two dienophiles via consecutive cycloaddition-1,2-elimination-cycloaddition, leading to the polycycle reported in eq 4. Furthermore, the diene (7) represents a conjunctive reagent for tandem Diels-Alder cycloaddition (eq 5).10

Sequential alkylation of the 9-fluorenyl anion with 1-bromo-2,4-pentadiene and with 2,3-dibromopropene leads to (9),13 which under Heck reaction conditions affords (10) (eq 6).

Reactions with Nitrogen Nucleophiles.

a-Methylene-b-lactams are synthesized from various 2-bromoallylamine derivatives using a catalytic amount of Palladium(II) Acetate and Triphenylphosphine under pressure of CO (eq 7).14 Other procedures involving the use of 2,3-dibromopropene and nitrogen nucleophiles have been reported.15-18

Reactions with Oxygen and Sulfur Nucleophiles.

Intramolecular radical cyclization reactions are widely used in organic synthesis for the construction of carbocycles.19 A rapid access to the hexahydrobenzofuran unit of avermectin A2b,20 which has a high antiparasitic activity, is shown in eq 8, where an important step is the construction of a 2-bromoallyl ether by phase transfer allylation with 2,3-dibromopropene.21

Reaction of PhSNa with 2,3-dibromopropene leads to 3-phenylthio-2-bromopropene, a useful reagent for radical allylations.22

Related Reagents.

2,3-Dichloropropene.


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2. Jeffery, T. TL 1989, 30, 2225.
3. Wang, K. K.; Chu, K.-H.; Lin, Y.; Chen, J.-H. T 1989, 45, 1105.
4. Piers, E.; Tillyer, R. D. JCS(P1) 1989, 2124.
5. Zhu, L.; Shaughnessy, K. H.; Rieke, R. D. SC 1993, 23, 525.
6. Piers, E.; Wong, T. JOC 1993, 58, 3609.
7. Hosomi, A.; Masunari, T.; Tominaga, Y.; Yanagi, T.; Hojo, M. TL 1990, 31, 6201.
8. Trost, B. M.; Chan, D. M. T. JACS 1982, 104, 3733.
9. Nishiyama, H.; Yokoyama, H.; Narimatsu, S.; Itoh, K. TL 1982, 23, 1267.
10. Trost, B. M.; Shimizu, M. JACS 1982, 104, 4299.
11. Hosomi, A.; Otaka, K.; Sakurai, H. TL 1986, 27, 2881.
12. Hosomi, A.; Hoashi, K.; Kohra, S.; Tominaga, Y.; Otaka, K., Sakurai, H. CC 1987, 570.
13. Burns, B.; Grigg, R.; Santhakumar, V.; Sridharan, V.; Stevenson, P.; Worakun, T. T 1992, 48, 7297.
14. Mori, M.; Chiba, K.; Okita, M.; Kayio, I.; Ban, Y. T 1985, 41, 375.
15. Knight, J.; Parsons, P. J. JCS(P1) 1987, 1237.
16. Rawal, V. H.; Michoud, C. TL 1991, 32, 1695.
17. Ghosh, T.; Hart, H. JOC 1988, 53, 2396.
18. Barluenga, J.; Foubelo, F.; Fananas, F. J.; Yus, M. JCS(P1) 1989, 553.
19. Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford, 1986.
20. Egerton, J. R.; Ostlind, D. A.; Blair, L. S.; Eary, C. H.; Suhayda, D.; Cifelli, S.; Riek, R. F.; Campbell, W. C. Antimicrob. Agents Chemother. 1979, 15, 372.
21. Parsons, P. J.; Willis, P.; Eyley, S. C. T 1992, 48, 9461.
22. Curran, D. P.; Yoo, B. TL 1992, 33, 6931.

Francesco Naso, Giuseppe Marchese & Vito Fiandanese

CNR Centre MISO, University of Bari, Italy



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