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
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 (Cy3
CHPh yields extended tetrathiafulvalene (exTTF) macrocyclic receptor 11
which exhibits one of the highest reported binding constants toward C60
- Bruns, R.; Kopf, J.; Köll, P. Chem. Eur. J. 2000, 6, 1337.
- Zeng, L.; Ye, Q.; Oberlies, N. H.; Shi, G.; Gu, Z.-M.; He, K.; McLaughlin, J. L. Nat. Prod. Rep. 1996, 13, 275.
- Dubost, C.; Markó, I. E.; Ryckmans, T. Org. Lett. 2006, 8, 5137.
- Deleuze, H.; Maillarda, B.; Mondain-Monval, O. Bioorg. Med. Chem. Lett. 2002, 12, 1877.
- Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: New York, 1986.
- Goundry, W. R. F.; Lee, V.; Baldwin, J. E. Tetrahedron Lett. 2002, 43, 2745.
- Pappo, R.; Allen, Jr., D. S.; Lemieux, R. U.; Johnson, W. S. J. Org. Chem. 1956, 21, 478.
- Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446.
- Chattopadhyay, S. K.; Maity, S; Panja, S. Tetrahedron Lett. 2002, 43, 7781.
- Isla, H.; Gallego, M.; Prez, E. M.; Viruela, R.; Ort, E.; Martin, N. J. Am. Chem. Soc. [Online early access]. DOI: 10.1021/ja910107m.