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John F Hartwig

Publications and source records attributed to John F Hartwig.

At least 19 recordsLinked to original sources
PubMed2006

Relative rates for the amination of eta3-allyl and eta3-benzyl complexes of palladium.

Reactions of nucleophiles with metal-bound hydrocarbyl pi-ligands bound in an eta3-fashion are key steps in a variety of carbon-carbon and carbon-heteroatom bond-forming reactions. To reveal factors that control the rates of reaction of nucleophiles with this type of ligand, the rates of reactions of an aromatic and an aliphatic amine with a series of eta3-allyl, eta3-benzyl, and eta3-phenethyl palladium complexes ligated by the bisphosphine (R)-BINAP to form allylic and benzylic amines were measured. These data showed that the less common addition to an eta3-benzyl complex is faster than the more common addition to an eta3-allyl complex. The relative rates of reaction followed the trend naphthylmethyl > naphthylethyl > benzyl > 1,1-dimethylallyl > allyl. Computational studies suggest that there is a correlation between the amount of positive charge at the site of nucleophilic attack and the rate of C-N bond formation.

Amination↗
PubMed2006

Palladium-catalyzed synthesis of aryl ketones by coupling of aryl bromides with an acyl anion equivalent.

Palladium-catalyzed couplings of aryl bromides with N-tert-butylhydrazones as acyl anion equivalents to form aryl ketones are reported. The coupling process occurs at the C-position of hydrazones to form N-tert-butyl azo compounds. Isomerization of these azo compounds to the corresponding hydrazones, followed by hydrolysis, gave the desired mixed alkyl aryl ketones. The selectivity of C- versus N-arylation was strongly influenced by the substituent on nitrogen. Arylation at carbon occurred with N-tert-butylhydrazones, whereas N-arylation occurred with N-arylhydrazones. The arylation of hydrazones containing primary and secondary alkyl groups, as well as aryl groups, gave the desired ketones in good yields after hydrolysis. Functional groups on the aromatic ring, such as alkoxy, cyano, trifluoromethyl, carboalkoxy, carbamoyl, and keto groups, were tolerated. This reaction likely occurs by C-C bond-forming reductive elimination from an intermediate containing an eta1-diazaallyl ligand.

Anions↗
PubMed2006

Ruthenium-catalyzed regiospecific borylation of methyl C-H bonds.

We report the regiospecific, ruthenium-catalyzed borylation of saturated terminal C-H bonds. Alkylboronates were obtained in 78-98% yields. The borylations of alkanes, trialkylamines, protected alcohols, and fluoroalkanes occurred regiospecifically at the methyl group that is least sterically hindered. In contrast to most organometallic C-H activation, the reactions of alkanes occurred in higher yields than the reactions of arenes. Reactions were conducted that probed steric and electronic effects on the alkyl borylation. These reactions showed that the borylation occurred preferentially at the methyl group that is least sterically hindered and most electron-deficient. Ruthenium compounds containing boryl ligands were synthesized, and one was characterized by X-ray crystallography. One of these compounds contained a rare bridging boryl ligand and served as a catalyst precursor for the borylation of octane.

Boron Compounds↗
PubMed2006

Highly efficient and functional-group-tolerant catalysts for the palladium-catalyzed coupling of aryl chlorides with thiols.

The cross-coupling reaction of aryl chlorides with aliphatic and aromatic thiols catalyzed by palladium complexes of the strongly binding bisphosphine CyPF-tBu ligand (1) is reported. Most of the reactions catalyzed by complexes of ligand 1 occur with turnover numbers that exceed those of previous catalysts by two orders of magnitude. The reactions occur with excellent yields, broad scope and high tolerance of functional groups. Coupling of aryl halides with thiols in the presence of low loadings of catalysts derived from other Josiphos type ligands, as well as ligands of other structural types, are also described.

Catalysis↗
PubMed2006

Hydroamination and hydroalkoxylation catalyzed by triflic acid. Parallels to reactions initiated with metal triflates.

Intermolecular additions of the O-H bonds of phenols and alcohols and the N-H bonds of sulfonamides and benzamide to olefins catalyzed by 1 mol % of triflic acid and studies to define the relationship between these reactions and those catalyzed by metal triflates are reported. Cyclization of an alcohol containing pendant monosubstituted and trisubstituted olefins catalyzed by either triflic acid or metal triflates form products from addition to the more substituted olefin, and additions of tosylamide catalyzed by triflic acid or metal triflates form indistinguishable ratios of the two N-alkyl sulfonamides.

Alkanes↗
PubMed2006

Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products.

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.

Allyl Compounds↗
PubMed2006

Palladium-catalyzed coupling of ammonia and lithium amide with aryl halides.

A mild, palladium-catalyzed coupling of aryl halides with ammonia or lithium amide to form primary arylamines as the major product is described. These reactions occurred with excellent selectivity for formation of the primary arylamine over formation of the diarylamine (9.5:1 to over 50:1 ratios of arylamine to diarylamine). In addition, the first organopalladium complex with a terminal -NH2 ligand has been isolated. This complex reductively eliminates to form arylamines.

Amides↗
PubMed2006

Carbon-oxygen bond formation between a terminal alkoxo ligand and a coordinated olefin. Evidence for olefin insertion into a rhodium alkoxide.

Preparation and reactivity of a series of bis(phosphine) rhodium(I) alkoxides stabilized by intramolecular olefin coordination are reported. {Rh(PEt3)2[kappa1:eta2-OCRR'(CH2)nCH=CH2]} (n = 1, 2) were prepared via alcoholysis of {Rh(PEt3)2[N(SiMe3)2]} by the corresponding alcohols HOCRR'(CH2)nCH=CH2. The in situ generated {Rh(PEt3)2[kappa1:eta2-OCRR'(CH2)2CH=CH2]} were not stable at ambient temperatures and decomposed in the presence of added PEt3 to afford 2,2-disubstituted-5-methylenetetrahydrofurans and [(PEt3)4Rh-H] in good to high yields. Kinetic and deuterium labeling results support a syn-oxyrhodation pathway via direct olefin insertion into a Rh-O bond, followed by rapid beta-hydride elimination. In comparison, {Rh(PEt3)2[kappa1:eta2-OCRR'CH2CH=CH2]} are isolated as stable crystals, and the Rh-olefin interactions are evidenced by an X-ray structure. Heating of these complexes generated [Rh(PEt3)2(eta2-allyl)] and the corresponding ketones in high yields following an apparent beta-allyl elimination pathway.

Journal Article↗
PubMed2006

Direct measurement of the thermodynamics of vinylarene hydroamination.

The thermodynamics for intermolecular hydroamination of vinylarenes with arylamines have been measured directly by conducting the addition processes, as well as cleavage of the addition products, under conditions in which amine, vinylarene, and phenethylamine are all present. The reaction of N-methylaniline with styrene is exothermic by about 10 kcal/mol but nearly thermoneutral in free energy. The free energies for additions of various primary arylamines to styrene and for additions of primary arylamines to indene, dihydronaphthalene, and two vinylarenes range from 1.3 to -3.5 kcal/mol (K = 0.16-155 M-1). The steric properties of the nucleophile significantly influenced the equilibrium constant for addition, but the electronic properties of the nucleophile had a minor effect on this equilibrium constant. These measurements have led to the first successful intermolecular addition of aniline to indene and 1,2-dihydronaphthalene and shed light on factors requiring consideration when choosing substrates and reaction conditions for this transformation.

Alkenes↗
PubMed2006

Organometallic chemistry of amidate complexes. accelerating effect of bidentate ligands on the reductive elimination of N-aryl amidates from palladium(II).

We report a series of arylpalladium complexes of acetamidate, sulfonamidate, and deprotonated oxazolidinone ligands that undergo reductive elimination with rates and yields that depend on the binding mode of the ancillary and amidate ligands. Complexes of the acetamidate ligands containing the bidentate phosphines DPPF and Xantphos as ancillary ligands undergo reductive elimination. The rate and yield were higher from the complex ligated by Xantphos, which contains a larger bite angle. In contrast, the analogous amidate complex containing a single sterically hindered monodentate ligand and a kappa2-bound amidate ligand does not undergo reductive elimination. This trend of faster reductive elimination from complexes containing bidentate ancillary ligands than from a complex with a single monodentate ancillary ligand is unusual and is consistent with an effect of the denticity of the ancillary ligand on the binding mode of the amidate. Complexes of sulfonamidate ligands underwent reductive elimination faster than complexes of acetamidates, and reductive elimination occurred from complexes containing both bidentate and monodentate ancillary ligands. Like reductive elimination from the acetamidate complexes, reductive eliminations from the sulfonamidate complexes were faster when the complexes possessed bidentate Xantphos and kappa1-sulfonamidate ligands.

Amides↗
PubMed2006

Tropene derivatives by sequential intermolecular and transannular, intramolecular palladium-catalyzed hydroamination of cycloheptatriene.

A consecutive inter- and intramolecular hydroamination of cycloheptatriene with primary aromatic amines, benzylic amines, and beta-phenethylamines occurs to produce pharmaceutically relevant tropene (8-azabicyclo[3.2.1]octene) frameworks in good to excellent yields. This reaction occurs in the presence of a catalyst generated from palladium trifluoroacetate, 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene and a mild acid. Mechanistic studies reveal that the overall process has some reversible steps, but that the rate of these reverse reactions are far slower than the rates of the forward catalytic process.

Amination↗
PubMed2006

Rhodium-catalyzed intramolecular, anti-Markovnikov hydroamination. Synthesis of 3-arylpiperidines.

The intramolecular anti-Markovnikov hydroamination of 1-(3-aminopropyl)vinylarenes in the presence of a readily available rhodium catalyst to form 3-arylpiperidines is reported. In contrast to intermolecular hydroamination of vinylarenes, which occurred in high yields in the presence of rhodium catalysts containing DPEphos, the intramolecular reaction occurred in high yield in the presence of [Rh(COD)(DPPB)]BF4 as catalyst. Reactants with substituents beta to the nitrogen occurred in high yield, and these reactions formed 3,5-disubstituted piperidines with high diastereomeric excess. The regiochemistry of these cyclizations contrasts with the regiochemistry of intramolecular hydroaminations catalyzed by lanthanide complexes, group III metal complexes, and platinum complexes, all of which have been reported to form cyclization products from Markovnikov addition.

Amination↗
PubMed2006

Palladium-catalyzed intermolecular alpha-arylation of zinc amide enolates under mild conditions.

The intermolecular alpha-arylation and vinylation of amides by palladium-catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of amides is reported. Reactions of three different types of zinc enolates have been developed. The reactions of aryl halides occur in high yields with isolated Reformatsky reagents generated from alpha-bromo amides, with Reformatsky reagents generated in situ from alpha-bromo amides, and with zinc enolates generated by quenching lithium enolates of amides with zinc chloride. This use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of amide arylation. The reactions occur at room temperature or 70 degrees C with bromoarenes containing cyano, nitro, ester, keto, fluoro, hydroxyl, or amino functionality and with bromopyridines. Moreover, the reaction has been developed with morpholine amides, the products of which are precursors to ketones and aldehydes. The arylation of zinc enolates of amides was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive, dimeric, Pd(I) complex [[P(t-Bu)3]PdBr]2.

Amides↗
PubMed2006

Reevaluation of the mechanism of the amination of aryl halides catalyzed by BINAP-ligated palladium complexes.

Two previous mechanistic studies of the amination of aryl halides catalyzed by palladium complexes of 1,1'-binaphthalene-2,2'-diylbis(diphenylphosphine) (BINAP) are reexamined by the authors of both studies. This current work includes a detailed study of the identity of the BINAP-ligated palladium complexes present in reactions of amines with aryl halides and rate measurements of these catalytic reactions initiated with pure precatalysts and precatalysts generated in situ from [Pd2(dba)3] and BINAP. This work reveals errors in both previous studies, and we describe our current state of understanding of the mechanism of this synthetically important transformation. 31P NMR spectroscopy shows that several palladium(0) species are present in the catalytic system when the catalyst is generated in situ from [Pd2(dba)3] and BINAP, and that at least two of these complexes generate catalytic intermediates. Further, these spectroscopic studies and accompanying kinetic data demonstrate that an apparent positive order in the concentration of amine during reactions of secondary amines is best attributed to catalyst decomposition. Kinetic studies with isolated precatalysts show that the rates of the catalytic reactions are independent of the identity and the concentration of amine, and studies with catalysts generated in situ show that the rates of these reactions are independent of the concentration of amine. Further, reactions catalyzed by [Pd(BINAP)2] with added BINAP are found to be first-order in bromoarene and inverse first-order in ligand, in contrast to previous work indicating zero-order kinetics in both. These data, as well as a correlation between the decay of bromobenzene in the catalytic reaction and the predicted decay of bromobenzene from rate constants of studies on stoichiometric oxidative addition, are consistent with a catalytic process in which oxidative addition of the bromoarene occurs to [Pd(BINAP)] prior to coordination of amine and in which [Pd(BINAP)2], which generates [Pd(BINAP)] by dissociation of BINAP, lies off the cycle. By this mechanism, the amine and base react with [Pd(BINAP)(Ar)(Br)] to form an arylpalladium amido complex, and reductive elimination from this amido complex forms the arylamine.

Amination↗
PubMed2006

Direct observation of beta-aryl eliminations from Rh(I) alkoxides.

beta-Aryl eliminations from a series of rhodium(I) alkoxides to form rhodium aryl complexes and free ketones are reported. Tertiary phenylmethoxide complexes [Rh(PEt3)n(OCPhRR')] (n = 2, 3) were prepared via alcoholysis of {Rh(PEt3)2[N(SiMe3)2} by the corresponding alcohols HOCPhRR' in the presence and absence of added PEt3. Heating of these complexes in the presence of added PEt3 generated the rhodium phenyl complex, (PEt3)3RhPh, and the corresponding ketones in good to high yields. Kinetic results are most consistent with irreversible beta-phenyl elimination from a bisphosphine-ligated rhodium alkoxide complex. Such bisphosphine complexes result from ligand dissociation from the trisphosphine complexes and have been isolated in some cases. The bisphosphine complexes are stabilized by Rh-Cphenyl interactions, as evidenced by an X-ray structure, and this structure with a metal-aryl interaction likely illustrates the pathway for C-C bond cleavage.

Journal Article↗
PubMed2006

Oxidative addition of phenyl bromide to Pd(BINAP) vs Pd(BINAP)(amine). Evidence for addition to Pd(BINAP).

The rates of oxidative addition of phenyl bromide to [Pd(BINAP)2] have been measured in the presence and absence of added amine to assess a previous hypothesis that addition to [Pd(BINAP)(amine)] is faster than addition to [Pd(BINAP)]. These data show that addition to the amine complex is not faster than addition to [Pd(BINAP)]. Instead, they are consistent with oxidative addition, even in the presence of amine, to [Pd(BINAP)] as the major pathway. These data underscore the value of studying the stoichiometric reactions of isolated complexes when assessing the mechanism of a catalytic process.

Benzene Derivatives↗
PubMed2006

A general and long-lived catalyst for the palladium-catalyzed coupling of aryl halides with thiols.

A general catalytic system for the coupling of aryl halides and sulfonates with thiols based on the use of the CyPF-t-Bu ligand (1) is reported. The reactions catalyzed by complexes of 1 occur in excellent yields with broad scope and exhibit extraordinary turnover numbers and high tolerance of functional groups. Turnover numbers usually exceed those of previous catalysts by 2 or 3 orders of magnitude. In addition, the reactions of aryl tosylates with alkane thiols to form aryl sulfides are reported for the first time. Finally, the synthesis of a diarylsulfide from two bromoarenes was accomplished using a hydrogen sulfide surrogate.

Anisoles↗