The synthesis and characterization of the new airstable precatalyst (L1)Ni(o-tol)Cl (C1; where L1 = JosiPhos CyPF-Cy) is reported, along with the results of a comparative reactivity survey involving C1 and analogous PAd-DalPhos-and DPPFcontaining precatalysts (C2 and C3, respectively) in representative nickel-catalyzed C(sp 2 )−N cross-coupling reactions. Precatalyst C1 was found to be competitive with, and in some cases complementary to, C2 in the monoarylation of ammonia and primary alkylamines with (hetero)aryl chlorides, including in otherwise challenging room temperature transformations. (Pseudo)halide comparison studies involving the cross-coupling of furfurylamine at room temperature revealed that in contrast to C2 precatalyst C1 performs less effectively with aryl bromides. Whereas C3 was found to be ineffective for such transformations, this DPPF-derived precatalyst proved superior to C1 and C2 in reactions involving the secondary dialkylamine test substrate morpholine.

Previous reports in the literature have established the utility of 1,1′-bis(diphenylphosphino)ferrocene (DPPF, L Ph ) 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 PR 2 -donor groups on catalytic performance in such transformations, a series of 10 structurally varied 1,1′bis(bis(alkyl/aryl)phosphino)ferrocene ancillary ligands (L X ) were systematically examined in selected competitive test crosscouplings of (hetero)aryl halides with furfurylamine, morpholine, and indole employing Ni(COD) 2 /L X catalyst mixtures. In addition to the excellent performance observed for the parent ligand L Ph in a number of the test transformations explored, selected dialkylphosphino (e.g., DiPPF, L iPr ) and meta-disubstituted diarylphosphino variants of L Ph also proved highly effective. In particular, the electron-deficient ligand variant L CF3 featuring 3,5-bis(trifluoromethyl)phenyl groups on phosphorus was found to exhibit superior catalytic performance relative to L Ph in most of the test transformations involving the N-arylation of indole. Our efforts to prepare Ni(II) precatalysts of the type (L X )Ni(o-tolyl)Cl, in analogy with known (L Ph )Ni(o-tolyl)Cl, by employing several literature methods met with mixed results. Whereas (L iPr )Ni(o-tolyl)Cl was prepared straightforwardly and was crystallographically characterized, the use of L CF3 or ligands featuring tert-butyl (L tBu ), o-tolyl (L o-tol ), or 4-methoxy-3,5dimethylphenyl (L OMe ) 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.

Base-metal catalysts capable of enabling the assembly of heteroatom-dense molecules by cross-coupling of primary heteroarylamines and (hetero)aryl chlorides,w hile sought-after given the ubiquity of unsymmetrical di-(hetero)arylamino fragments in pharmacophores,a re unknown. Herein, we disclose the new "double cage" bisphosphine PAd2-DalPhos (L2). The derived air-stable Ni II precatalyst C2 functions well at lowl oadings in challenging test CÀNcross-couplings with established substrates,and facilitates the first Ni-catalyzed CÀNcross-couplings of primary five-or six-membered ring heteroarylamines and activated (hetero)aryl chlorides,w ith synthetically useful scope that is competitive with Pd catalysis.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

We report herein on the synthesis of new heteroaryl analogues of PAd-DalPhos and related bis(di(otolyl)phosphino) ancillary ligand variants based on pyridine or thiophene backbone structures, and their application in nickelcatalyzed C(sp 2 )-N cross-couplings under challenging reaction conditions. The 3,4-disubstituted thiophene-based ancillary ligand ThioPAd-DalPhos (L8) was observed to be particularly effective in the nickel-catalyzed C(sp 2 )-N cross-coupling of primary alkylamines, and the derived precatalyst (L8)NiCl(otolyl) (C2) was found to offer improved performance versus the related PAd-DalPhos-derived precatalyst C1 in such transformations. In using C2, cross-couplings of various primary alkylamines and (hetero)aryl-X electrophiles (X = Cl, Br, OTs) proceeded under unprecedentedly mild reaction conditions (0.25−0.50 mol % Ni), including examples conducted at room temperature. Also reported herein are the results of our combined experimental/DFT computational study directed toward gaining insight regarding the improved catalytic performance of C2 versus C1.

The nickel-catalyzed cyclization of in situ generated ortho-chlorobenzophenone hydrazone derivatives, to afford 3-(hetero)aryl-1H-indazoles, is documented for the first time. The product 1H-indazoles can be transformed subsequently in a one-pot procedure into 1,3-di(hetero)aryl-1H-indazoles via copper-catalyzed N-arylation with (hetero)aryl bromides.