Negishi-Baba Cross-Coupling

This is another very useful cross-coupling reaction that relies on organozinc reagents with Pd catalysts. Some key highlights during recent years are discussed in the following paragraphs. 

They also successfully conducted benzylic Negishi-Baba coupling on 2-methylbenzo[fi]thiophen, 2-methylbenzofuran, indole, and benzo[r/] imidazole. 

Similar work was reported by Coldham and Leonori, who applied this methodology to the synthesis of the alkaloid anabasine [171b]. These workers used tBujP-HBF as the ligand. 

In 2010, Andreas Leitner and coworkers [174] at BASF reported the preparation of a very stable 2-pyridylzinc bromide (an sp organometallic nucleophile) on a multi-kilogram scale using Rieke technology and its application in the Negishi-Baba cross-coupling reaction. 

It was also reported in 2011 that diaryl teUurides could be coupled with organozincs using palladium and copper catalysts [178]. The products were obtained in moderate yields. 

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Scheme 1.16 (a) General conditions for the Negishi-Baba cross-coupling reaction, (b) The proposed mechanism for the Negishi-Baba cross-coupling arylation procedure [12a],... 

Scheme 1.54 Nickel-catalyzed Negishi-Baba cross-coupling arylation of secondary alkylzinc halides by...

Scheme 1.57 Negishi-Baba cross-coupling arylation step in the large-scale synthesis of a naphthylacetic acid CRTH2 receptor antagonist by Hoffmann-La Roche [180].

Negishi-Baba Cross-Coupling 1.4.8.1 Synthesis of 1 -Mesityinaphthalene... 

A direct and satisfactory procedure for tertiary alkyl-alkynyl coupling has been developed by Negishi and Baba, who used trialkynylaluminums readily obtainable from the corresponding alkynyllithiums and anhydrous AICI3 [92]. For instance, tris(l-hexynyl)aluminum underwent a remarkably clean reaction with 1-adamantyl bromide to produce cross-coupled product 96 in 96 % yield. It is noteworthy that the reaction enables novel geminal alkyl-alkynylation of ketones this reaction should find a considerable application in natural product synthesis (Sch. 60). 

Negishi, E., Takahashi, T., Baba, S., Van Horn, D. E., Okukado, N. Nickel- or palladium-catalyzed cross coupling. 31. Palladium- or nickel-catalyzed reactions of alkenylmetals with unsaturated organic halides as a selective route to arylated alkenes and conjugated dienes scope, limitations, and mechanism. J. Am. Chem. Soc. 1987,109, 2393-2401. 

Alkenyl-alkenyl cross-coupling. Baba and Negishi have prepared a catalyst from this Pd(II) complex and 2 equiv. of diisobutylaluminum hydride that promotes this coupling reaction. Tetrakis(triphenylphosphine)palladium(0) is inactive, as is material prepared in situ from palladium chloride, triphenylphos-phine and HAKr-CtHg) . A nickel catalyst prepared from Ni(acac)2, PfCnHsja, and diisobutylaluminum hydride is somewhat less efficient. The coupling Involves (E)-alkenylalanes (4, 158, 159) and alkenyl halides. The products are (E,E)- and (E,Z)-dienes. 

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