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A New Efficient Catalytic System for the ChemoselectiveCobalt-Catalyzed Cross-Coupling of Aryl GrignardReagents with Primary and Secondary Alkyl Bromides
Gerard Cahiez,* Christophe Chaboche, Christophe Duplais, and Alban Moyeux
Organic Letters, 2009, 11, 277-280.
Carl Deutsch @ Wipf Group Page 1 of 10 2/15/2009
Background
Carl Deutsch @ Wipf Group Page 2 of 10 2/15/2009
Background
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The Cahiez GroupLocation:Université de Cergy-PontoiseSite de Neuville-sur-OiseCergy-Pontoise CedexNorth West of Paris
Research Interest:Organometallic Chemistry
Iron- / Cobalt- catalyzedcross coupling reactions
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Title Paper
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Optimization
X
1.1 eq. PhMgBr
catalytic systemTHF, 0°C
Ph
entry Xcatalytic system
5 mol-%yield
1 I CoCl2 10
2 I Co(acac)3 14
3 I Co(acac)3/TMEDA = 1:1 94
4 I CoCl2/Ligand = 1:1 93
5 Br Co(acac)3/TMEDA = 1:1 92
6 Br CoCl2/Ligand = 1:1 73
7 Br Co(acac)3/Et3N = 1:5 15
8 Br Co(acac)3/DABCO = 1:1 37
9 Br Co(acac)3/dppe 1:3 traces
NMe2
NMe2ligand
N
NDABCO
O Oacac
Ph2PPPh2 dppe
Me2NNMe2TMEDA
can be upscaled to 50 mmolconcentration: 0.5M
Oshima conditions give loweryields
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Alk-Br + ArMgBr
5 mol-% Co(acac)35 mol-% TMEDA
THF, 0°C, 40 minAlk-Ar
entry yieldalkyl halide product
123
X2
Ph2
95% (X = I)94% (X= Br)10% (X = Cl)
4 Br6
6
MeO
96%
567 X Ph
94% (X = I)92% (X= Br)4% (X = Cl)
8910
Br
FG
93%97% (FG = 4-OMe)88% (FG = 2-OMe)
1112 X 4
Ph4
98% (X = Br)10% (X= OTs)
13 Br Ph trace
Scope and Limitations
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Tolerates several functionalities
Sterically hindered systemsgive low yields
Scope and Limitations
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Comparison with other methods
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Summary
• Development of Cobalt catalyzed cross coupling of Aryl grignard reagentswith primary and secondary alkyl bromides accomplished
•Several functionalities (e.g. Ester, amides, ketones) are tolereated
•Products obtained in high yields
Major drawbacks:
Chlorines/Tosylates or tertiary alkyl bromides can not be used
Catalytic cycle is unknown and further investigations are required
Carl Deutsch @ Wipf Group Page 10 of 10 2/15/2009
