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