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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
Publication History
Publication Date:
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
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1a
Current address: Johnson and Johnson Pharmaceutical Research and Development, Chemical Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
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1b
Current address: CMC Solutions, Overhemstraat 3, 3320 Hoegarden, Belgium.
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Giri R.Maugel N.Li J.-J.Wang D.-H.Breazzano SP.Saunders LB.Yu J.-Q. J. Am. Chem. Soc. 2007, 129: 3510 -
3a
Giles R.Green IR.van Eeden N. Eur. J. Org. Chem. 2004, 4416 -
3b
Guiso M.Bianco A.Marra C.Cavarischia C. Eur. J. Org. Chem. 2003, 3407 -
3c
Agejas-Chicharro J,Bueno Melendo AB,Camp NP,Gilmore J,Lamas-Peteira C,Timms GH, andWilliams AC. inventors; PCT Int., WO 03053948. -
3d
Michaelidis MR.Schoenleber R.Thomas S.Yamamoto DM.Britton DR.MacKenzie R.Kebabian JW. J. Med. Chem. 1991, 34: 2946 -
4a For a historical account of the development of the Kumada coupling, see:
Tamao K. J. Organomet. Chem. 2002, 653: 23 - For publications with comprehensive references on Pd- and Ni-catalyzed Kumada coupling, see:
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4b
Tasler S.Lipshutz BH. J. Org. Chem. 2003, 68: 1190 -
4c
Boelm VPW.Weskamp T.Gstoettmayr CWK.Herrmann WA. Angew. Chem. Int. Ed. 2000, 39: 1602 -
4d
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:
Zhou W.Gumina G.Chong Y.Wang J.Schinazi RF.Chu CK. J. Med. Chem. 2004, 47: 3399 - 8 In the absence of the nitrile Pd-catalyzed coupling of unprotected halobenzoic acid 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:
Dounay AB.Overman LE. Chem. Rev. 2003, 103: 2945
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.