Aliphatic Bromoalkenes

Product Name	Product Code	CAS Number	Chemical Formula	Molecular Weight	Structure
4-Bromo-1-butene	FB03113	5162-44-7	C4H7Br	135.00
5-Bromo-1-pentene	FB06176	1119-51-3	C5H9Br	149.03
6-Bromo-1-hexene	FB07085	2695-47-8	C6H11Br	163.06
7-Bromo-1-heptene	FB09446	4419-09-3	C7H13Br	177.08
8-Bromo-1-octene	FB08261	2695-48-9	C8H15Br	191.11

Brominated alkenes are highly useful organic chemistry building blocks, having multiple uses in variety of synthetic transformations. A range of four to eight-carbon brominated alkenes are supplied by Carbosynth. The bromine atom can be displaced by nucleophiles, act as a precursor to carbon centred radicals and participate in organometallic chemistry reactions via the formation of Grignard reagents, organozinc reagents or bromine-lithium exchange processes to yield organolithium reagents. The alkene double bond can participate in multiple processes, including hydrogenation, hydroboration-oxidation, ozonolysis, Lemieux-Johnson oxidation to an aldehyde, halogenation, halohydrin formation, epoxidation, dihydroxylation and olefin metathesis.

Köll and co-workers have used the Grignard reagent formed from 4-bromo-1-butene FB03113 to elongate aldehyde 1, yielding diastereomers 2 and 3 enroute to partially hydroxylated 2,5-disubstituted bis-tetrahydrofuran 4 and its three diastereomers (Scheme 1).¹ These bis-tetrahydrofuran core units feature in annonaceous acetogenins, complex natural products with diverse biological properties, including interesting cytotoxic, antitumor, antimicrobial, antimalarial, antifeedant, pesticidal and immunosuppressive activities.^1,2


In a similar fashion, Markó has used alkene (5) as a building block in the natural product synthesis of the polyhydroxylated macrolide (+)-Aspicilin (Scheme 2).³ Grignard formation, followed by copper-catalysed epoxide opening furnished a chiral undecenol, which was silyl-protected and the alkene converted into a primary alcohol via a hydroboration-oxidation sequence.


Free radical dehalogenation reactions followed by intramolecular carbon-carbon coupling are powerful sequences in organic synthesis since a wide range of functional groups are tolerated, negating the need for protection and deprotection sequences.^4,5 The reductive cyclisation of 6-bromohex-1-ene (3) to yield methylcyclopentane has been reported, using a new polymer-supported thiol reagent (Pol-SH, Scheme 3) in the presence of triethylsilane.⁴

Baldwin and colleagues have used 5-bromo-1-pentene FB06176 in the total synthesis of cytotoxic sponge alkaloid hachijodine 6 via intermediate alkyne 5, Scheme 4.⁶ The alkyne is formed by alkylation of lithiated 3-picoline with bromide FB06176, followed by Lemieux-Johnson oxidation⁷ (dihydroxylation and diol cleavage) to reveal the aldehyde, which is further transformed into 5 by treatment with dimethyl(1-diazo-2-oxopropyl)phosphonate.

Olefin metathesis is a versatile methodology for carbon-carbon bond formation,⁸ used frequently to synthesize ring systems, especially those with 7- or 8-membered rings which are difficult to access by other methodologies. 4-Bromo-1-butene FB03113 has been used in the synthesis of oxocin-annulated coumarin 8, via alkylation of 7 and subsequent ring-closing metathesis, Scheme 5.⁹

In supramolecular chemistry, 7-bromo-1-heptene FB09446 has been used in the synthesis of a macrocyclic receptor that associates C₆₀ with micromolar affinity (Scheme 6).¹⁰ After monoalkylation of aryl-diol 9 with alkene FB09446 and conversion of the anthraquinone aryl unit (Ar) to the extended tetrathiafulvalene moiety (10, Ar’), cyclisation using the first-generation Grubb’s catalyst (Cy₃P)₂RuCl₂CHPh yields extended tetrathiafulvalene (exTTF) macrocyclic receptor 11 which exhibits one of the highest reported binding constants toward C₆₀.

References:
1. Bruns, R.; Kopf, J.; Köll, P. Chem. Eur. J. 2000, 6, 1337.
2. Zeng, L.; Ye, Q.; Oberlies, N. H.; Shi, G.; Gu, Z.-M.; He, K.; McLaughlin, J. L. Nat. Prod. Rep. 1996, 13, 275.
3. Dubost, C.; Markó, I. E.; Ryckmans, T. Org. Lett. 2006, 8, 5137.
4. Deleuze, H.; Maillarda, B.; Mondain-Monval, O. Bioorg. Med. Chem. Lett. 2002, 12, 1877.
5. Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: New York, 1986.
6. Goundry, W. R. F.; Lee, V.; Baldwin, J. E. Tetrahedron Lett. 2002, 43, 2745.
7. Pappo, R.; Allen, Jr., D. S.; Lemieux, R. U.; Johnson, W. S. J. Org. Chem. 1956, 21, 478.
8. Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446.
9. Chattopadhyay, S. K.; Maity, S; Panja, S. Tetrahedron Lett. 2002, 43, 7781.
10. Isla, H.; Gallego, M.; Prez, E. M.; Viruela, R.; Ort, E.; Martin, N. J. Am. Chem. Soc. [Online early access]. DOI: 10.1021/ja910107m.