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DOI: 10.1055/s-2007-985572
Carboxylate-Directed Kumada Coupling of an Acetaldehyde Synthon with 2-Bromobenzoates Used towards the Synthesis of Isochromanes
Publikationsverlauf
Publikationsdatum:
13. August 2007 (online)
Abstract
This letter describes the Kumada coupling of bromobenzoic acid derivatives with the acetaldehyde enolate synthon (1,3-dioxolan-2-ylmethyl)magnesium bromide. The lithium carboxylate salt shows the highest reactivity in the coupling reaction while addition of t-BuOLi affords optimal selectivity. During this work, we have observed a strong directing effect of the sodium carboxylate function which can be useful in differentiating electronically similar diaryl bromides.
Key words
directed Kumada coupling - carboxylate-directed Pd cross-coupling - isochromane synthesis
- 1a
Current address: Johnson and Johnson Pharmaceutical Research and Development, Chemical Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
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Current address: CMC Solutions, Overhemstraat 3, 3320 Hoegarden, Belgium.
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- 4b
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Huang J.Nolan SP. J. Am. Chem. Soc. 1999, 121: 9889 - 5 The Grignard, 8, is stable despite the β-alkoxy function but shows remarkably low reactivity. For
example, reaction with aldehydes takes place only at 60 °C:
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have been reported:
Bugamagin NA.Luzikova EV. J. Organomet. Chem. 1997, 532: 271 - 12 Coordination of carboxylates to Pd(II) oxidative addition intermediates has been described
in Heck coupling reactions:
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References and Notes
An extensive screening protocol was conducted. Some examples of the catalysts that were evaluated include: Cl2Ni(PPh3)2, Cl2Ni(dppp), Cl2Ni(dppe) [dppe: 1,2-bis(diphenylphosphino)ethane], Ni(acac)2, Ni(acac)2-Imes+Cl- (Imes: 1,3-dimesitylimidazol-2-ylidene), Ni/C, in THF, Bu2O, toluene, NMP, at 60-80 °C.
7The catalysts screened include: Pd(PPh)4, Pd(OAc)2-P(cy)3, Pd(OAc)2-Pt-Bu3, PdCl2-dppf [1,1-bis(diphenylphos-phino)ferrocene], Pd2(dba)3-P(tol)3, Pd2(dba)3-P(furyl)3.
9Solvent screens with NMP, DMSO, toluene, trifluoro-toluene, MTBE, gave no reaction under these reaction conditions.
10Attempts to convert 8 into the corresponding Zn, boronic acid or trifluoroborate derivatives, to evaluate its coupling under Pd catalysis, were not successful.
11Variations on the ratio of 4:9 from 80:20 to 92:8 were observed, reaction time varied between five hours and 24 hours, while the conversion varied more than 20%.
13The product 4 can be isolated in ca 98% purity in 92% yield by crystallization from EtOAc-heptane. The styrene derivative 9 can be thus completely removed.