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

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.