Search

Steric reduction principles were applied in N-phosphinoamidine ligand (PN) design to significantly improve 1-octene selectivity in ethylene tri-/tetramerization chromium catalysis. Novel phosphole- and phospholane-based PN-ligands were prepared and used to synthesize discrete chromium complexes which were fully characterized. The highest 1-octene producing Cr/PN/MMAO catalyst system compares favorably with the benchmark Cr/PNP/MMAO system generating a higher overall product selectivity at equivalent yields. Characterization of the structurally related cyclic phosphine-based Cr/PN pre-catalysts revealed that 1-octene selectivity varied inversely with the ligand bite angle, albeit over a small range. In contrast, the acyclic phosphine-based catalyst produces significantly less 1-octene than expected based on its small bite angle. This disparity signals a breakdown of bite angle as the main 1-octene selectivity geometric descriptor and suggests that the key selectivity driver occurs further away from the metal center requiring more sophisticated modeling efforts to properly account for the differences.

The Ni-catalyzed N-arylation of b-fluoroalkylamines with broad scope is reported for the first time. Use of the air-stable pre-catalyst (PAd2-DalPhos)Ni(o-tol)Cl allows for reactions to be conducted at room temperature (25 oC, NaOtBu), or by use of a commercially available dual-base system (100 oC, DBU/NaOTf), to circumvent decomposition of the N-(b-fluoroalkyl)aniline product. The mild protocols disclosed herein feature broad (hetero)aryl (pseudo)halide scope (X = Cl, Br, I, and for the first time phenol derived electrophiles), encompassing base sensitive substrates and enantioretentive transformations, in a manner that is unmatched by any previously reported catalyst system.

The first nickel-catalyzed N-arylation of amides with (hetero)aryl (pseudo)halides employing an organic amine base is described. By using a bis(cyclooctadienyl)nickel/8-[2-(dicyclohexylphosphinyl)phenyl]-1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphaadamantane catalyst mixture in combination with DBU/NaTFA as a dual-base system, a diversity of (hetero)aryl chloride, bromide, tosylate, and mesylate electrophiles were successfully cross-coupled with structurally diverse primary amides, as well as a selection of secondary amide, lac­tam, and oxazolidone nucleophiles.

The Ni(II) precatalyst (C1) featuring the phosphonite ancillary ligand Phen-DalPhos (L1) was employed in the cross-coupling of (hetero)anilines with (hetero)aryl chlorides and in the diarylation of...

Base-metal catalysts capable of enabling the assembly of heteroatom-dense molecules by cross-coupling of primary heteroarylamines and (hetero)aryl chlorides, while sought-after given the ubiquity of unsymmetrical di(hetero)arylamino fragments in pharmacophores, are unknown. Herein, we disclose the new "double cage" bisphosphine PAd2-DalPhos (L2). The derived air-stable NiII pre-catalyst C2 functions well at low loadings in challenging test C-N cross-couplings with established substrates, and facilitates the first Ni-catalyzed C-N cross-couplings of primary five- or six-membered ring heteroarylamines and activated (hetero)aryl chlorides, with synthetically useful scope that is competitive with Pd catalysis.

The base metal-catalyzed C-N cross-coupling of bulky α,α,α-trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under-developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air-stable Ni(II) pre-catalyst incorporating the optimized ancillary ligand PhPAd-DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state-of-the-art Pd catalysts, including room temperature cross-couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).

The development of Ni-catalyzed C-N cross-couplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air-stable (L)NiCl(o-tol) pre-catalysts (L=PhPAd-DalPhos and PAd2-DalPhos), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X=Cl, Br, I, OTs, and OC(O)NEt2 ) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide C-N cross-coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.

We report herein on the results of our combined experimental/computational study regarding the catalytic performance of PAd-DalPhos (L1) in nickel-catalyzed ammonia arylation for primary aniline synthesis. Primary arylamine C–N reductive eliminations occurring from arylnickel(II) parent amido complexes of the type (L)Ni(Ph)(NH2) were modeled by use of density-functional theory (DFT) methods, for a series of L1 derivatives. The dual aims were to assess the effect of structural modifications to L1 on potentially rate-limiting C–N reductive elimination and to identify promising candidates for experimental inquiry. Increasing the steric demand of the Paryl groups from o-tolyl (in L1) to mesityl (in L16) resulted in a significant lowering of the barrier to C–N reductive elimination (ΔG⧧RE), which can be attributed in part to interactions between the ligand Paryl groups and the nickel-bound amido ligand, as observed in noncovalent interaction (NCI) plots of the reductive elimination transition-state structures....

We report herein on the synthesis of new heteroaryl analogues of PAd-DalPhos and related bis(di(o-tolyl)phosphino) ancillary ligand variants based on pyridine or thiophene backbone structures, and their application in nickel-catalyzed C(sp2)-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(sp2)-N cross-coupling of primary alkylamines, and the derived precatalyst (L8)NiCl(o-tolyl) (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...

The present contribution describes the systematic structural diversification of the κ2-P,N DalPhos ligand family in an effort to improve catalytic efficiency in the monoarylation of ammonia and acetone. The study is focused primarily on modifying the backbone phenylene linker, while retaining the same bite angle and steric bulk as the Mor-DalPhos ligand through the use of P(1-Ad)2 and morpholine donors. Eight new variants of Mor-DalPhos were prepared; two of these feature a pyridine linker (L1, L2), and five others feature either electron-donating (L3, L4) or electron-withdrawing (L5–L7) substituents on the phenylene linker. Additionally, thiomorpholino substitution (L8) was performed to investigate the effects of a possible tridentate coordination mode. Precatalyst complexes of the general formula LPd(cinnamyl)Cl were prepared and characterized in both solution and solid state. Solution studies demonstrated a significant degree of lability in the Pd–N bond, whereby dynamic behavior is seen to be dependent on the nature of the ligand backbone. The utility of these new ligands in the palladium-catalyzed monoarylation of ammonia or acetone was then surveyed. Notably, pyridine-derived ligand variants (L1, L2) were observed to out-perform parent Mor-DalPhos in the latter transformations.

The Ni-catalyzed Csp2–N cross-coupling of NH substrates and (hetero)aryl (pseudo)halides for the synthesis of (hetero)anilines is in the midst of a resurgence. Reactivity breakthroughs that have been achieved in this field within the past five years have served to establish Ni catalysis as being competitive with, and in some cases superior to, more well-established Pd- or Cu-based protocols. Whereas the repurposing of useful ancillary ligands from the Pd domain has been the most frequently employed approach in the quest to develop effective Ni-based catalysts for such transformations, considerable progress has been made as of late in the design of ancillary ligands tailored specifically for use with Ni. Bisphosphine ancillary ligands have proven to be well-suited for such an approach, given their modular and facile syntheses; several variants have emerged recently that are particularly effective in enabling a range of otherwise challenging Ni-catalyzed Csp2–N cross-couplings. This Perspective presents a c...

The competitive catalytic screening of 18 known and newly prepared Mor-DalPhos ligand variants in the palladium-catalyzed cross-coupling of chlorobenzene with aniline, octylamine, morpholine, indole, ammonia, or acetone is presented, including ligands derived from the new secondary phosphine HP(Me2Ad)2 (Me2Ad = 3,5-dimethyladamantyl). Although triarylphosphine ancillary ligand variants performed poorly in these test reactions, ligands featuring either PAd2 or P(Me2Ad)2 donors (Ad = 1-adamantyl) gave rise to superior catalytic performance. Multiple Mor-DalPhos variants proved effective in cross-couplings involving aniline, octylamine, or morpholine; conversely, only a smaller subset of ligands proved useful in related cross-couplings of indole, ammonia, or acetone. In the case of the N-arylation of indole, a Mor-DalPhos ligand variant featuring ortho-disposed PAd2 and dimethylmorpholino donor fragments (L13) proved superior to all other ligands surveyed, including the parent ligand Mor-DalPhos (L5). Conversely, L5 was found to be superior to all other ligands in the palladium-catalyzed monoarylation of ammonia. Ligand L6 (i.e., the P(Me2Ad)2 variant of L5) proved superior to all other ligands in the monoarylation of acetone and, with the exception of indole N-arylation, was the most broadly useful of the Mor-DalPhos ligands surveyed herein.

We report herein on the synthesis and catalytic application of a family of o-phenylene-bridged bisphosphine ancillary ligands featuring a bulky N-heterocyclic phosphine (NHP) donor fragment paired with an adjacent PR2 donor group (R = alkyl, aryl), whereby the incorporation of phosphorus into either a saturated or unsaturated heterocyclic ring serves as a means of modulating the donicity of the NHP fragment. Screening of these ancillary ligands in representative nickel-catalyzed C(sp2)–N cross-coupling test reactions allowed for the identification of one variant, featuring a saturated NHP structure and an adjacent diphenylphosphino donor group (i.e., NHP-DalPhos), as being particularly effective in reactions involving primary alkylamines. Notably, application of the derived precatalyst (NHP-DalPhos)NiCl(o-tolyl) (C1) enabled the typically challenging monoarylation of structurally diverse primary alkylamines with (hetero)aryl chlorides or bromides at room temperature. Also described are the results of our ...

The successful application of (DPEPhos)Ni(mesityl)Br (C1) as a pre-catalyst in the Suzuki–Miyaura cross-coupling of heteroaryl chlorides or bromides and heteroaryl boronic acids is reported. The use of C1 in this context allows for such reactions to be conducted under mild conditions (2 mol% Ni, 25 °C), including cross-couplings leading to unsymmetrical biheteroaryls. Successful transformations of this type involving problematic pyridinyl boronic acid substrates (10 mol% Ni, 60 °C) are also described.

The influence of ancillary ligand and nickel oxidation state in the nickel-catalyzed C(sp2)–N cross-coupling of aryl chlorides is examined by use of experimental and DFT methods for the first time, focusing on (L)NiCl and (L)Ni(o-tolyl)Cl pre-catalysts (PAd-DalPhos, L1; dppf, L2). Whereas Ni(II) pre-catalysts generally out-performed Ni(I) species in our study, the viability and in some cases superiority of Ni(I) pre-catalysts in challenging aminations is established. Computational analyses support the viability of Ni(0)/Ni(II) cycles featuring rate-limiting C–N reductive elimination, as well as parallel Ni(I)/Ni(III) mechanisms involving rate-limiting C–Cl oxidative addition.

A catalyst system capable of effecting the cross-coupling of ammonia or primary alkylamines with (hetero)aryl sulfamates, carbamates, or pivalates is reported for the first time. The air-stable nickel(II) pre-catalyst C1 tolerates a broad spectrum of heterocyclic functionality within both reaction partners, as well as ether, nitrile, pyrrole, trifluoromethyl, and boronate ester substituents. In the case of reactions involving primary alkylamines and (hetero)aryl sulfamates and carbamates, room-temperature cross-couplings were achieved.

Synthesis and characterization of the new air-stable pre-catalyst (DPEPhos)Ni(2-mesityl)Br (C1) is reported, along with the application of this pre-catalyst in the cross-coupling of secondary amines/azoles with activated (hetero)aryl chlorides to afford tertiary (hetero)anilines. The performance of C1 in these cross-couplings is competitive with some of the best and/or most widely employed nickel catalysts for such transformations.

The first examples of stoichiometric dehydrogenative B-H/C(sp3 )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2 -P,N)Pt(η3 -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a PtII -H intermediate engages in C(sp3 )-H bond activation-induced dehydrogenation.

The synthesis and characterization of a series of structurally varied N-phosphinoamidinate-ligated cobalt complexes is described, along with the successful application of these and a related iron complex as precatalysts in the isomerization–hydroboration of terminal, geminal, and internal alkenes. These reactions proceed under mild conditions (23–65 °C), at relatively low base-metal loadings (1–5 mol %), typically without cosolvent, and with high terminal hydroboration selectivity across a broad spectrum of branched alkenes. With some of the alkene substrates examined, the N-phosphinoamidinate-ligated precatalysts employed herein are shown to provide alternative terminal selectivity versus other previously reported precatalyst classes for such transformations. Reports of terminal-selective metal-catalyzed alkene isomerization–hydroboration disclosed thus far in the literature employ pinacolborane (HBPin); while effective in the system herein, we also report the first examples of such transformations emplo...

The synthesis and characterization of the new air-stable 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 DPPF-containing precatalysts (C2 and C3, respectively) in representative nickel-catalyzed C(sp2)–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.

The utility of RockPhos, Ad-BippyPhos, JosiPhos (CyPF-tBu), and Mor-DalPhos in palladium-catalyzed C–O cross-coupling reactions involving aliphatic alcohols and (hetero)aryl halides under analogous conditions was examined, both at room temperature and at elevated temperature (90 °C). In general, the RockPhos-based catalyst system proved superior, especially at room temperature, but catalysts based on the other ligands examined also proved effective across a range of C–O cross-couplings, in some cases providing better catalytic performance than RockPhos. New reactivity was established in terms of the scope of room temperature reactions. Proof-of-principle examples of such cross-couplings involving aryl mesylates were also demonstrated.

Palladium-catalysed C(sp2)–N cross-coupling (that is, Buchwald–Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp2)–N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known., The development of highly effective Earth-abundant catalysts for C(sp 2)-N cross-coupling represents an on-going challenge in synthetic chemistry. Here, the authors report a nickel complex containing a bisphosphine ancillary ligand allowing room-temperature couplings of amines and ammonia with a range of electrophiles.

The use of (L)Ni(o-tolyl)Cl precatalysts (L = PAd-DalPhos or CyPAd-DalPhos) enables the C(sp2)–O cross-coupling of primary, secondary, or tertiary aliphatic alcohols with (hetero)aryl electrophiles, including unprecedented examples of such nickel-catalyzed transformations employing (hetero)aryl chlorides, sulfonates, and pivalates. In addition to offering a competitive alternative to palladium catalysis, this work establishes the feasibility of utilizing ancillary ligation as a complementary means of promoting challenging nickel-catalyzed C(sp2)–O cross-couplings, without recourse to precious-metal photoredox catalytic methods.

A mild and efficient protocol for the assembly of tetra-substituted 5-trifluoromethylpyrazoles is presented, involving halogenation at the 4-position of readily prepared tri-substituted 5-trifluoromethylpyrazoles to give 4-halo-1-phenyl-5-trifluoromethyl pyrazoles, and subsequent palladium-catalyzed Negishi or Buchwald-Hartwig cross-couplings to install carbon or nitrogen-based 4-substituents. Key to the success of these challenging cross-couplings is the use of XPhos and JosiPhos CyPF-tBu ligands, respectively.

N-Aryl derivatives of edaravone were identified as potentially effective small molecule inhibitors of tau and beta-amyloid aggregation in the context of developing disease-modifying therapeutics for Alzheimer's disease (AD). Palladium-catalyzed hydrazine monoarylation protocols were then employed as an expedient means of preparing a focused library of 21 edaravone derivatives featuring varied N-aryl substitution, thereby enabling structure-activity relationship (SAR) studies. On the basis of data obtained from two functional biochemical assays examining the effect of edaravone derivatives on both fibril and oligomer formation, it was determined that derivatives featuring an N-biaryl motif were four-fold more potent than edaravone.

A crystallographically characterized three-coordinate, formally 14 electron Pt(II) complex 1 featuring terminal amido ligation is reported. Computational analysis revealed relatively weak π donation from the amide lone pair to platinum and supports a 14-electron assignment for 1. Stoichiometric reactivity studies confirmed the viability of net O-H and C-H addition across, as well as isonitrile insertion into, the terminal platinum-amido linkage of 1.

We report herein on our synthetic, structural, and catalytic investigations of new P,S-DalPhos ligands featuring pairings of phosphorus and sulfur donor groups as well as new sulfur-containing analogues of the previously reported P,N-ligands Me-DalPhos and Mor-DalPhos, featuring a 2,3-disubstituted thiophenyl backbone. In examining the catalytic performance of these new sulfur-containing ligands in the Buchwald–Hartwig amination of octylamine, aniline, or ammonia with 4-chlorotoluene, noteworthy differences in reactivity behavior relative to Me-DalPhos and Mor-DalPhos were observed.

Structurally diverse (hetero)aryl chloride, bromide, and tosylate electrophiles were employed in the Ni-catalyzed monoarylation of ammonia, including chemoselective transformations. The employed JosiPhos/[Ni(cod)2] catalyst system enables the use of commercially available stock solutions of ammonia, or the use of ammonia gas in these reactions, thereby demonstrating the versatility and potential scalability of the reported protocol. Proof-of-principle experiments established that air-stable [(JosiPhos)NiCl2] precatalysts can be employed successfully in such transformations.

The application of a Mor-DalPhos/palladium catalyst system in the one-pot, multicomponent assembly of substituted indoles from ortho-chlorohaloarenes, alkyl ketones (including acetone), and primary amines is reported. The described protocols offer improved substrate scope in all three reaction components, under more mild conditions and without the need for an additional drying agent. Also reported are the first examples of such multicomponent reactions where all reactants are combined at the start of the reaction, without the need for inert atmosphere reaction conditions.

The synthesis and structural characterization of three-coordinate iron(II) and cobalt(II) complexes supported by new N-phosphinoamidinate ligands is reported, along with the successful application of these complexes as precatalysts for the challenging room-temperature hydrosilylation of carbonyl compounds to afford alcohols upon workup. Under the rigorous screening conditions employed (0.015 mol % Fe) for the reduction of acetophenone, the well-defined iron(II) amido precatalyst 2b, featuring bulky N-2,6-diisopropylphenyl and di-tert-butylphosphino moieties within the N-phosphinoamidinate ligand, exhibited exceptional catalytic performance. Further experimentation revealed that the yield achieved in the hydrosilylation of acetophenone employing 2b was unaltered when conducting reactions in the absence of light, in the presence of excess mercury, or under solvent-free conditions. Notably, precatalyst 2b was found to exhibit the broadest substrate scope reported to date for such room-temperature iron-cataly...

For the first time examples of enolate α-arylation employing aryl mesylate coupling partners and amination of inexpensive phenol derivatives with primary aliphatic amines are developed.

A mixture of tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) and 5-(di-tert-butylphosphino)-1′,3′,5′-triphenyl-1′H-[1,4′]bipyrazole (Bippyphos) is shown to be a robust and efficient catalyst system for the hydroxylation of structurally diverse (hetero)aryl halides under mild conditions and with broad substrate scope. Included in this reactivity survey is the successful synthesis of substituted benzofurans and related heteroatomic derivatives, which are formed via the hydroxylation of 2-haloalkynylarenes. Notably, a significant number of the reactions reported herein proceed at room temperature, and we have demonstrated that it is possible to conduct reactions on the benchtop under air using unpurified solvents with negligible loss in reactivity versus related transformations conducted under inert atmosphere conditions. We also report herein the first crystallographically characterized (Bippyphos)Pd(II) complex, which confirms the ability of this synthetically useful ligand to adopt a bidentate binding motif in a manner similar to Buchwald’s biarylphosphine ligand class.

An examination of the [{Pd(cinnamyl)Cl}(2)]/Mor-DalPhos (Mor-DalPhos = di(1-adamantyl)-2-morpholinophenylphosphine) catalyst system in Buchwald-Hartwig aminations employing ammonia was conducted to better understand the catalyst formation process and to guide the development of precatalysts for otherwise challenging room-temperature ammonia monoarylations. The combination of [{Pd(cinnamyl)Cl}(2)] and Mor-DalPhos afforded [(κ(2)-P,N-Mor-DalPhos)Pd(η(1)-cinnamyl)Cl] (2), which, in the presence of a base and chlorobenzene, generated [(κ(2)-P,N-Mor-DalPhos)Pd(Ph)Cl] (1 a). Halide abstraction from 1 a afforded [(κ(3)-P,N,O-Mor-DalPhos)Pd(Ph)]OTf (5), bringing to light a potential stabilizing interaction that is offered by Mor-DalPhos. An examination of [(κ(2)-P,N-Mor-DalPhos)Pd(aryl)Cl] (1 b-f) and related precatalysts for the coupling of ammonia and chlorobenzene at room temperature established the suitability of 1 a in such challenging applications. The scope of reactivity for the use of 1 a (5 mol %) encompassed a range of (hetero)aryl (pseudo)halides (X = Cl, Br, I, OTs) with diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro, trifluoromethyl, and nitrile), including chemoselective arylations.

The first nickel-catalyzed N-arylation of amides with (hetero)aryl (pseudo)halides is reported, enabled by use of the air-stable pre-catalyst (PAd-DalPhos)Ni(o-tolyl)Cl (C1). A range of structurally diverse primary amides and lactams were cross-coupled successfully with activated (hetero)aryl chloride, bromide, triflate, tosylate, mesylate, and sulfamate electrophiles.

A mild and efficient protocol for the assembly of tetra-substituted 5-trifluoromethylpyrazoles is presented, involving halogenation at the 4-position of readily prepared tri-substituted 5-trifluoromethylpyrazoles to give 4-halo-1-phenyl-5-trifluoromethyl pyrazoles, and subsequent palladium-catalyzed Negishi or Buchwald–Hartwig cross-couplings to install carbon or nitrogen-based 4-substituents. Key to the success of these challenging cross-couplings is the use of XPhos and JosiPhos CyPF-tBu ligands, respectively.

Preparation of enols: when treated with [{Pd(cinnamyl)Cl}(2)]/cataCXium A (nBuPAd(2), Ad=adamantyl) under an atmosphere of CO, aryl ketones react with aryl halides in a carbonylative C-O coupling reaction to form (Z)-vinyl benzoates.

Variants of the DalPhos [2-aminophenylbisadamantyl)phosphine] ligand family were examined in a palladium-catalyzed carbonylative amination reaction using inexpensive carbon monoxide and ammonia as reagents. As a result of this survey, the Pyr-DalPhos ligand was identified as being effective for the selective aminocarbonylation of aryl bromides with ammonia, as well as primary and secondary alkylamines. A variety of primary aromatic, heteroaromatic and N-substituted benzamides were formed in moderate to good yields. As part of this study, a (Mor-DalPhos)Pd-benzoyl complex was prepared and crystallographically characterized, thereby showing the viability of the carbonyl insertion step.

We report the extension and optimization of the [Pd(cinnamyl)Cl]2/DalPhos catalyst system, previously found effective for the mono-α-arylation of acetone, to the mono-α-arylation of a variety of carbonyl-containing compounds with aryl halides and heteroaryl halides. Aryl methyl ketones, heteroaryl methyl ketones, propiophenones, malonates, and methoxyacetone can be α-arylated under relatively mild conditions and in good yields. We also report the limitations of the ligand/catalyst system towards other classes of carbonyl-containing compounds.

We report on the application of the [Pd(cinnamyl)Cl]2/Mor-DalPhos catalyst system in the Buchwald–Hartwig amination of (hetero)aryl chlorides with primary or secondary amines conducted either under aqueous conditions without the use of co-solvents and/or surfactants or under solvent-free conditions (52 examples). We have established that reactions of this type can be conducted without the rigorous exclusion of air, and in the case of the solvent-free reactions, we have demonstrated that appropriately selected liquid and solid reagents can be employed successfully.

The efficacy of phosphine-free Pt precatalysts including PtCl2 and (COD)PtCl2 in promoting the cyclohydroamination of primary as well as secondary alkyl/arylamines tethered to α-olefins is demonstr...

The phosphino–phenolate complex (κ2-{2-i-Pr2PC6H4}O)Ir(COD) (COD = η4-1,5-cyclooctadiene; 1) is shown to be an effective precatalyst for the intramolecular hydroamination of unactivated alkenes with pendant secondary alkylamines, providing either pyrrolidine or piperidine heterocycles in high isolated yields. While monitoring the progress of a selected test reaction of this type, a significant induction period (~3 h) was observed; variable-temperature 1H and 31P NMR studies (25–100 °C) under catalytically relevant conditions revealed no new metal-containing species. In an effort to develop an enantiopure variant of 1, a synthetic route to the chiral (κ2-P,O)Ir(COD) complex (7), which features a 1-aryl-2,5-dialkylphospholane structure derived from (2S,5S)-2,5-hexanediol cyclic sulfate, was developed. The structure of 7 was confirmed by use of single-crystal X-ray diffraction techniques. While 7 failed to provide enantioselectivity in the intramolecular hydroamination of unactivated alkenes with pendant secondary alkylamines, the activity of 7 was found to be comparable to that of 1.

The catalytic utility of [κ2-{3-iPr2P-2-O-indene}Rh(COD)] (COD = η4−1,5-cyclooctadiene) 1a in the hydroformylation of styrenes was examined. Complex 1a was shown to be an effective pre-catalyst in benzene and tetrahydrofuran, exhibiting good conversions to aldehyde and high branched-to-linear selectivity for styrene, 4-chlorostyrene, and 4-methylstyrene under reasonably mild conditions (1000 psi syngas; 1.8 mol% Rh, 45 °C, 2–5 h). Under analogous conditions, the iridium congener of 1a proved inactive for hydroformylation. The synthesis and crystallographic characterization of the new complex [κ2-{2-iPr2PC6H4O}Rh(COD)] 2 is also reported; the catalytic performance of 2 in the hydroformylation of styrene was found to be comparable to that of 1a under similar catalytic conditions.

Lithiation of 2-dimethylaminoindene followed by quenching with [( R )-(1,1′-binaphthalene-2,2′-diyl)]chlorophosphite and treatment with triethylamine afforded the crystallographically characterized enantiopure P,N-indene 3 in 71% isolated yield. In the course of rhodium coordination chemistry studies involving 3 , the formation of the isolable complex [(κ 2 - P , N - 3 )(κ 1 - P ,N- 3 )RhCl] ( 7 ) (81%) was observed, thereby confirming the propensity of this new ligand to form L n Rh( 3 ) 2 complexes. Such coordination chemistry behavior may contribute in part to the generally poor catalytic performance exhibited by mixtures of 3 and rhodium precursor complexes in the asymmetric hydrogenation and hydrosilylation studies described herein.

A series of Ru-based complexes supported by P,N-substituted indene or indenide ligands have been prepared and tested for activity in the atom transfer radical addition of CCl4 to alkenes. The catalytic performance was found to be influenced by the charge and substitution pattern of the P,N ligand and other coligands, as well as the nature of the counteranion, with the best of these catalysts being effective at low catalyst loadings and under mild conditions.

Heating of [(COD)M(κ2-3-PiPr2-2-NMe2-indene)]+X- (M = Rh or Ir; X = BF4, PF6; COD = η4-1,5-cyclooctadiene) in a mixture of water and THF (48 h, 60 °C) afforded the neutral (COD)M(κ2-P,O) complexes (M = Rh, 5a, 80%; M = Ir, 5b, 74%). Similarly, thermolysis of [(COD)M(κ2-3-P(S)iPr2-2-NMe2-indene)]+BF4- (M = Rh or Ir) in a mixture of water and CH2Cl2 (14 h, 60 °C) produced the neutral (COD)M(κ2-P(S),O) complexes (M = Rh, 13a, 91%; M = Ir, 13b, 90%). Subsequent preparation of 1-PiPr2-2-indanone (8, 91%) enabled the non-hydrolytic synthesis of 5b in 70% isolated yield via treatment with 0.5[(COD)IrCl]2 in the presence of NEt3. Lithiation of (o-PiPr2)phenol followed by quenching with 0.5[(COD)IrCl]2 afforded the neutral (COD)Ir(κ2-P,O) complex 10 (91%). Single-crystal X-ray diffraction data are provided for 5b, 10, 13a, and 13b. Whereas 5a, 13a, and 13b performed poorly as catalysts for the hydrogenation of alkenes, the known complex (COD)Ir(OPh)(PCy3) 2 as well as 5b and 10 proved to be excellent catalysts for...