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Evaluating 1,1′-Bis(phosphino)ferrocene Ancillary Ligand Variants in the Nickel-Catalyzed C–N Cross-Coupling of (Hetero)aryl Chlorides

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journal contribution
posted on 15.01.2017, 00:00 by Jillian S. K. Clark, Christopher N. Voth, Michael J. Ferguson, Mark Stradiotto
Previous reports in the literature have established the utility of 1,1′-bis­(diphenylphosphino)­ferrocene (DPPF, LPh) in the nickel-catalyzed cross-coupling of (hetero)­aryl electrophiles with primary or secondary amines. In an effort to evaluate the effect of varying the PR2-donor groups on catalytic performance in such transformations, a series of 10 structurally varied 1,1′-bis­(bis­(alkyl/aryl)­phosphino)­ferrocene ancillary ligands (LX) were systematically examined in selected competitive test cross-couplings of (hetero)­aryl halides with furfurylamine, morpholine, and indole employing Ni­(COD)2/LX catalyst mixtures. In addition to the excellent performance observed for the parent ligand LPh in a number of the test transformations explored, selected dialkylphosphino (e.g., DiPPF, LiPr) and meta-disubstituted diarylphosphino variants of LPh also proved highly effective. In particular, the electron-deficient ligand variant LCF3 featuring 3,5-bis­(trifluoromethyl)­phenyl groups on phosphorus was found to exhibit superior catalytic performance relative to LPh in most of the test transformations involving the N-arylation of indole. Our efforts to prepare Ni­(II) precatalysts of the type (LX)­Ni­(o-tolyl)­Cl, in analogy with known (LPh)­Ni­(o-tolyl)­Cl, by employing several literature methods met with mixed results. Whereas (LiPr)­Ni­(o-tolyl)Cl was prepared straightforwardly and was crystallographically characterized, the use of LCF3 or ligands featuring tert-butyl (LtBu), o-tolyl (Lo‑tol), or 4-methoxy-3,5-dimethylphenyl (LOMe) groups on phosphorus under similar conditions resulted in poor conversion to product and/or the formation of poorly soluble materials, highlighting the limitations of this commonly used precatalyst design.