Kevin H Shaughnessy

Kevin H Shaughnessy
University of Alabama | UA · Department of Chemistry

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103
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Publications (103)
Article
Full-text available
Synthesis of hierarchically porous carbons incorporating metal nanoparticles can be carried out by a “one-pot” process in which the metal precursor is mixed with polymer precursors and structure directing agents, that undergoes a sol-gel self-assembly polymerization and then pyrolyzed under an inert atmosphere. Such syntheses are potentially cheape...
Article
A series of air-stable [(Np3P)Pd(Ar)Br]2 (Np = neopentyl) and (Np3P)Pd(Ar)(amine)Br complexes (amine = morpholine and isobutylamine) have been prepared and tested as precatalysts for the coupling of sterically demanding aryl bromides and aniline derivatives. The complexes are more active than the catalyst generated in situ from Pd2(dba)3 and PNp3....
Article
Steric properties of crystallographically and computationally determined structures of linear palladium(0) and square planar palladium(II) complexes of di(tert-butyl)neopentylphosphine (P(t-Bu)2Np), tert-butyldineopentylphosphine (P(t-Bu)Np2), and trineopentylphosphine (PNp3) have been determined. Structures of linear palladium(0) complexes show th...
Article
Enolizable ketones have been identified as effective activators for palladium(II) precatalysts in the coupling of aryl bromides and aniline. N-Arylation reactions catalyzed by [(DTBNpP)PdCl2]2 (DTBNpP = (di-(tart-butyl)neopentylphosphine) and PEPPSI-IPR precatalysts are activated by the addition of acetone, mesityl oxide, and 3-pentanone. 3-Pentano...
Article
Phosphines are widely used ligands in transition metal-catalyzed reactions. Arylphosphines, such as triphenylphosphine, were among the first phosphines to show broad utility in catalysis. Beginning in the late 1990s, sterically demanding and electron-rich trialkylphosphines began to receive attention as supporting ligands. These ligands were found...
Chapter
Palladium‐catalyzed amination of aryl halides is widely used in the synthesis of N‐aryl amine derivatives. N‐Aryl amines have important applications as pharmaceuticals, agricultural chemicals, and electronic materials. This chapter provides a summary of the mechanism, the optimal choice of catalyst, and the scope of this important reaction. Applica...
Article
A series of [(PNp3)Pd(Ar)Br]2 complexes (PNp3 = trineopentylphosphine, Ar = 4-tolyl, 4-tert-butylphenyl, 2-tolyl, 4-methoxy-2-methylphenyl, 2-isopropylphenyl, and 2,6-dimethylphenyl) were synthesized and structurally characterized by X-ray crystallography and density functional theory optimized structures. The trineopentylphosphine ligand is able t...
Article
Palladium catalysts have become central to modern organic synthesis, particularly in the context of cross‐coupling reactions to form C−C and C‐heteroatom bonds. The development of highly efficient catalyst systems has seen a transition from the use of in situ‐generated catalysts derived from a ligand source and palladium precursor to the use of pre...
Article
Air-stable [(R3P)PdCl2]2 complexes with di-tert-butylneopentylphosphine (DTBNpP, 1a) or trineopentylphosphine (TNpP, 1b) ligands have been applied to Suzuki cross-coupling reactions, and the mechanism of their conversion to the active LPd⁰ catalyst species has been studied. Precatalysts 1a,b provide effective catalysts for Suzuki cross-coupling of...
Article
Full-text available
Described is the synthesis of metal (Ni, Cr, and Mn) doped macro/mesoporous carbon monoliths by co-polymerization of transition metal complexes with resorcinol/formaldehyde and subsequent pyrolysis. Two salen ligands were synthesized via reaction of ethylene diamine (EDA) and 1,6-diaminohexane (DAH) with 2,4-dihydroxybenzaldehyde to give 4,4′-((1E,...
Article
The mechanism of the bis(trineopentylphosphine)palladium(0) (Pd(PNp3)2)-catalyzed coupling of aryl halides and aniline derivatives was studied in an effort to understand the role of substrate steric effects on the reaction. Prior studies had shown that the rate of Pd/PNp3-catalyzed coupling of aryl bromides and aniline derivatives was largely unaff...
Article
A method for the selective cross-dimerization of terminal aryl alkynes with propargyl alcohols to afford linear E-enynol products is reported. The [Pd(µ-κ2-O,O-OAc)(κ2-C,P-(t-Bu)2PCH2C(Me)2CH2)]2 complex selectively affords E-5-aryl-2-en-4-yn-1-ol products in good yields under mild conditions with high chemo-, regio-, and stereoselectivity. In cont...
Article
The influence of water on deprotonation and ionic mechanisms of a Heck alkynylation and its resultant E-factors were investigated. Estimation of the Hatta modulus, MH < 0.02, in cationic deprotonation, anionic deprotonation, and the ionic mechanism each separately confirmed an infinitely slow rate of reaction with respect to the diffusive flux with...
Chapter
C12H28BF4P (MW 290.13) 1S/C12H27P.BF4/c1-10(2,3)13(11(4,5)6)12(7,8)9;2-1(3,4)5/h1-9H3;/q;-1/p+1 InChIKey = YTJUCJAUJCXFTN-UHFFFAOYSA-O (ligand precursor for palladium-catalyzed cross-coupling reactions) Physical Data: mp 261 °C (decomposes). Solubility: soluble in methylene chloride, chloroform; slightly soluble in THF; insoluble in hexane, toluene...
Chapter
C12H27P (MW 202.32) 1S/C12H27P/c1-10(2,3)13(11(4,5)6)12(7,8)9/h1-9H3 InChIKey = BWHDROKFUHTORW-UHFFFAOYSA-N (supporting ligand for palladium-1 and rhodium-catalyzed2 cross-coupling reactions) Physical Data: mp 30 °C; bp 102–103 °C/13 Torr; d 0.812 g cm−3. Solubility: sol in most organic solvents; insol in H2O. Form Supplied: colorless liquid or low...
Article
The influence of water on the catalysis of biphasic Heck alkynylation, a family of palladium-catalyzed carbon-carbon bond formations, was investigated. Kinetic theory derived from Hatta moduli and pseudo-stationary-state approximations discovered that water, in coordination, reductive elimination, and product dissociation reaction steps of the depr...
Article
Full-text available
α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability of β-dicarbonyl anions to bind to...
Article
Aqueous-biphasic catalysis offers the potential for safer and more environmentally sustainable synthetic processes. In addition, hydrophilic supporting ligands allow homogeneous catalysts to be readily separated from organic products and potentially reused. The synthesis of two new water-soluble ligand precursors, di-tert-butyl(4-sulfonatobenzyl)ph...
Article
Full-text available
Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful method to attach groups...
Conference Paper
Flow chemistry, important to the global chemicals and materials sectors, depends on the symbiosis between chemical reaction engineering and organic synthesis. Chemistry and engineering principles are needed to design therapeutics and microscale devices for a broad cross-section of society problems. Studying chemical reactions on-chip has advantages...
Article
Di-tert-butylneopentylphosphine (DTBNpP) and palladium(II) acetate provide an efficient catalytic system for the α-arylation of ketones. Aryl bromides were coupled with ketones using 0.25–0.5 mol-% Pd(OAc)2/DTBNpP in toluene at 50 °C, whereas aryl chlorides required a higher catalyst loading (0.5–2.0 mol-%) and a higher temperature (80 °C). Couplin...
Article
The use of neopentyl phosphine ligands were examined in the coupling of aryl bromides with alkenes. Di-tert-butylneopentylphosphine (DTBNpP) was found to catalyze Heck couplings with aryl bromides at ambient temperature. In the Heck coupling of cyclic alkenes, the degree of alkene isomerization was found to be controlled by the choice of ligand wit...
Chapter
The copper-catalyzed arylation and vinylation of nitrogen nucleophiles is a highly versatile method for the construction of sp2 C–N bonds. Copper-catalyzed C–N bond formation has an extensive history and the field has been reinvigorated with the development of ligand-promoted catalyst systems that provide general and effective reactions under relat...
Article
The palladium-catalyzed ortho monobromination and iodination of single E or Z geometric isomers of substituted diaryl ketoxime ethers [Ar1C(Ar2) = N–OCH3] have been accomplished in good yield (64–82% isolated yield). A minor amount of di-ortho-halogenation side product is produced in this reaction (0–10%). The aromatic ring that is halogenated is t...
Article
The copper-catalyzed arylation and vinylation of nitrogen nucleophiles is a highly versatile method for the construction of sp²C–N bonds. Copper-catalyzed C–N bond formation has an extensive history and the field has been reinvigorated with the development of ligand-promoted catalyst systems that provide general and effective reactions under relati...
Article
The engineering of reaction mixtures that ensure the solubility of inorganic salt byproducts without compromising the reactivity is a grand challenge for continuous flow manufacturing in upstream pharmaceuticals and fine chemicals process development. Aqueous cross-coupling reactions are possible solutions. We report the study of an aqueous phase P...
Article
Introduction Aqueous-Phase Cross-Coupling Using Hydrophilic Catalysts Cross-Coupling in Aqueous Media Using Hydrophobic Ligands Heterogeneous Catalysts in Aqueous Media Special Reaction Conditions Homogeneous Aqueous-Phase Modification of Biomolecules Conclusion References
Article
Trineopentylphosphine (TNpP) in combination with palladium provides a highly effective catalyst for the Buchwald-Hartwig coupling of sterically demanding aryl bromides and chlorides with sterically hindered aniline derivatives. Excellent yields are obtained even when both substrates include 2,6-diisopropyl substituents. Notably, the reaction rate i...
Article
A high-yielding stereospecific route to the synthesis of single geometric isomers of diaryl oxime ethers through Suzuki coupling of N-alkoxyimidoyl iodides is described. This reaction occurs with complete retention of the imidoyl halide geometry to give single E or Z isomers of diaryl oxime ethers. The Sonogashira coupling of N-alkoxyimidoyl iodide...
Article
In this unit, an efficient method for the synthesis of alkyne-modified nucleosides in an aqueous solvent system is described. The method allows direct palladiumcatalyzed alkynylation of readily available unprotected 8-bromo-2'-deoxyguanosine (8-BrdG), 8-bromo-2'-deoxyadenosene (8-BrdA), 8-bromoadenosine (8-BrA), and 5-iodo-2'-deoxyuridine (5-IdU) p...
Article
Hierarchically porous materials are of interest in a wide range of applications. If the materials are electronic or ionic conductors such materials are of interest as electrodes for use in fuel cells, flow batteries, electrocatalysis, and pseudo/supercapacitors. We have demonstrated the synthesis of hierarchically porous carbon, metal and metal oxi...
Article
Palladium-catalyzed Heck couplings between 5-iodouridine and alkenes were carried out in aqueous media in the presence of triethylamine under phosphine-free conditions to give the desired products in high yields. In the absence of phosphine ligand, triethylamine appears to play a critical role in both generating the active catalyst species and serv...
Article
The B form of DNA exists in equilibrium with the Z form and is mainly affected by sequence, electrostatic interactions, and steric effects. C8-purine substitution shifts the equilibrium toward the Z form though how this interaction overcomes the unfavorable electrostatic interactions and decrease in stacking in the Z form has not been determined. H...
Chapter
[60633-21-8] C13H29P (MW 216.3) InChI = 1S/C13H29P/c1-11(2,3)10-14(12(4,5)6)13(7,8)9/h10H2,1-9H3 InChIKey = JBGICSFDKZAWFJ-UHFFFAOYSA-N (ligand for palladium-catalyzed cross-coupling reactions1, 2)Physical Data: bp 43–47 °C, 0.1 Torr.Solubility: soluble in organic solvents; insoluble in water.Form Supplied in: commercially available in pure form, a...
Article
The air-stable complex Pd(η(3)-allyl)(DTBNpP)Cl (DTBNpP = di(tert-butyl)neopentylphosphine) serves as a highly efficient precatalyst for the arylation of amines and enolates using aryl bromides and chlorides under mild conditions with yields ranging from 74% to 98%. Amination reactions of aryl bromides were carried out using 1-2 mol % Pd(η(3)-allyl...
Article
A variety of applications of C-alkynylated nucleosides has prompted the continuing development of efficient synthetic methods for their preparation. We report an efficient andenvironmentally benign Sonogashira coupling reaction for alkynylation of unprotected halonucleosides in an aqueous solvent. The combination of Pd(OAc)2, CuI, and TXPTS [trisod...
Article
Phosphine-based catalysts play an important role in many metal-catalyzed carbon-carbon bond formation reactions yet reliable values of their bond energies are not available. We have been studying homogeneous catalysts consisting of a phosphine bonded to a Pt, Pd, or Ni. High level electronic structure calculations at the CCSD(T)/complete basis set...
Article
2A palladium-catalyzed α-arylation of amides is reported. Intermolecular arylation of N,N-dimethylamides and lactams occurs using aryl halides, silylamide base, and a palladium catalyst. Intramolecular arylation of N-(2-halophenyl)amides occurs using alkoxide base and a palladium catalyst. The palladium catalyst was formed in situ from Pd(dba)2 (db...
Article
Full-text available
A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2'-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus s...
Article
Hydrophilic ligands and their application in aqueous-phase metal-catalyzed reactions are studied. The Rhône-Poulenc aqueous-phase hydroformylation process, aqueous-phase catalysis has been applied to a wide range of catalytic processes. This work has demonstrated that nearly any catalytic reaction involving late transition metals can be adapted to...
Article
3-(Di-tert-butylphosphonium)propane sulfonate (DTBPPS) and 3-(diadamantylphosphonium)propane sulfonate (DAPPS) are air-stable pre-ligands for aqueous-phase palladium-catalyzed cross-coupling reactions. Both DTBPPS and DAPPS were found to give active catalysts for the Sonogashira coupling of aryl bromides at room temperature and 4-chloroanisole at 8...
Chapter
[782479-45-2] C27H27F5N2 (MW 474.5) InChI = 1S/C27H27F5N2/c1-13-9-15(3)25(16(4)10-13)33-7-8-34(26-17(5)11-14(2)12-18(26)6)27(33)19-20(28)22(30)24(32)23(31)21(19)29/h9-12,27H,7-8H2,1-6H3InChIKey = HSIQYZZZKQLXLK-UHFFFAOYSA-N(stable precursor to 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene,1 a commonly used ligand in Pd-catalyzed coupling react...
Article
The use of neopentylphosphine ligands in the palladium-catalyzed Suzuki, Sonogashira, Heck, and Hartwig–Buchwald couplings of aryl bromides and chlorides are reported. Di-tert-butylneopentylphosphine (DTBNpP) provided highly active catalysts for the coupling of aryl bromides at mild temperatures. Trineopentylphosphine, an air-stable trialkylphosphi...
Article
Tri(2,4-dimethyl-5-sulfonatophenyl)phosphine trisodium (TXPTS·Na3) and tri(4-methoxy-2-methyl-5-sulfonatophenyl)phosphine trisodium (TMAPTS·Na3) both provide more active catalysts for Suzuki and Sonogashira couplings of aryl bromides in aqueous solvents than tri(3-sulfonatophenyl)phosphine trisodium (TPPTS·Na3). In the Heck coupling, TXPTS·Na3 prov...
Article
The first selective palladium-catalyzed phenylselenylation of aryl bromides using a tin-free phenylselenolate source is reported. High selectivity for the desired asymmetric diaryl selenide is achieved using a catalyst derived from palladium and a Josiphos-type ligand with (PhSe)2/NaBH4 as the phenylselenylating agent. Aryl bromides are phenylselen...
Chapter
C12H27P (MW 202.32) InChI = 1S/C12H27P/c1-10(2,3)13(11(4,5)6)12(7,8)9/h1-9H3 InChIKey = BWHDROKFUHTORW-UHFFFAOYSA-N (supporting ligand for palladium-1 and rhodium-catalyzed2 cross-coupling reactions) Physical Data: mp 30 °C; bp 102–103 °C/13 Torr; d 0.812 g cm−3. Solubility: sol in most organic solvents; insol in H2O. Form Supplied: colorless liqui...
Article
Zwitterionic imidazolium salts have been synthesized bearing alkylsulfonate and alkylcarboxylate substituents and used as precursors to water-soluble metal−carbene complexes. Reaction of the zwitterionic imidazolium compounds with Ag2O gave bis(imidazol-2-ylidene)silver complexes. These compounds have been characterized spectroscopically and by ele...
Article
Allyl bromides are efficiently coupled with aryl and aliphatic aldehydes in the presence of manganese metal, collidine hydrochloride, bis(diisopropylphosphino)ethane and chromium dichloride. Homoallylic alcohols are isolated in good to excellent yields directly from the reaction mixture.
Article
Water is an attractive solvent for metal-catalyzed reactions with both economic and environmental sustainability benefits. In addition, the use of a hydrophilic catalyst in an aqueous-biphasic solvent system provides the opportunity to easily recover, and potentially recycle, the catalyst species. The feasibility of cross-coupling reactions catalyz...
Article
Di(tert-butyl)neopentylphosphine (DTBNpP) in combination with palladium sources provided catalysts with comparable or better activity for the Hartwig-Buchwald amination of aryl bromides than tri(tert-butyl)phosphine (TTBP) under mild conditions. DTBNpP also provided effective catalysts for amination reactions of aryl chlorides at elevated temperatu...
Article
A family of water-soluble palladacycles was prepared from benzylamine or benzaldehyde imine ligands bearing hydrophilic functional groups. The palladacycles derived from N,N-dimethyl-p-hydroxybenzylamine (7) and sodium 4-(N-benzylideneamino)benzenesulfonate (10) gave active catalysts for the Suzuki coupling of aryl bromides and activated aryl chlor...
Article
The cover picture shows Little River Falls in the Little River Canyon National Preserve in Northeastern Alabama. Water is the solvent of life, and increasingly, water is being applied as a solvent in organic synthesis. Shown going over the falls are typical substrates for palladium-catalyzed cross-coupling reactions and their products collected in...
Article
The combination of t-Bu-Amphos and RhCl3.3H2O gave the first highly recyclable catalyst for the coupling of aryl- and vinylboronic acids with aldehydes in aqueous solvents.
Article
In the Suzuki arylations of unprotected halonucleosides in aqueous media, 8-bromo-2'-deoxyguanosine (8BrdG) couplings were slower to reach completion than the corresponding 8-bromo-2'-deoxyadenosine (8BrdA) couplings. The guanine moiety has an acidic proton, which under our Suzuki conditions (pH congruent with 10) may be deprotonated to give an ani...
Article
In the Suzuki arylations of unprotected halonucleosides in aqueous media, 8-bromo-2'-deoxyguanosine (8BrdG) couplings were slower to reach completion than the corresponding 8-bromo-2'deoxyadenosine (8BrdA) couplings. The guanine moiety has an acidic proton, which under our Suzuki conditions (PH congruent to 10) may be deprotonated to give an anion...
Article
Di-t-butyl(ferrocenylmethyl)phosphine (1) has been isolated and structurally characterized. This ligand was found to be reasonably air stable as a solid and it has been shown to possess electron donating ability similar to that of tri-i-propylphosphine. A palladium catalyst bearing this ligand performed room temperature Suzuki–Miyaura coupling reac...
Article
Ionic liquid solvents N-hexylpyridinium bistrifylimide ([C6pyr][Tf2N]] and 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim][PF6]) promoted the displacement of anionic ligands by pyridine derivatives in trans-(Ph3P)2Rh(CO)NO3 to a much greater extent than did dichloromethane. Thus, addition of a slight excess of 2-fluoropyridine to trans-(Ph...
Article
Oxidative addition of methyl iodide to Vaska’s complex in the ionic liquids 1-butyl-3-methylimidazolium triflate [C4mim][OTf], [C4mim] bis(trifluormethylsulfonyl)imide [Tf2N], and N-hexylpyridinium [C6pyr][Tf2N] occurred cleanly to give the expected Ir(III) oxidative addition product. Pseudo-first order rate constants were determined for the oxidat...
Article
The palladium-catalyzed hydroesterification of olefins occurs efficiently in a range of ionic liquid media. Selectivities ranging from 5–7:1 for the linear ester were obtained with styrene in a range of IL solvents. The use of ILs allowed the catalyst to be easily separated from the organic product by either extraction or distillation. The (Ph3P)2P...
Article
Water has attracted significant attention as an alternative solvent for homogeneous metal-catalyzed reactions because it is a non-toxic, nonflammable solvent that can allow for simplified recovery of homogeneous catalysts. The use of water as a solvent in palladium-catalyzed cross-coupling reactions is of great academic and industrial interest. Pal...
Article
Sterically demanding, water-soluble alkylphosphine ligands 2-(di-tert-butylphosphino)ethyltrimethylammonium chloride (t-Bu-Amphos) and 4-(di-tert-butylphosphino)-N,N-dimethylpiperidinium chloride (t-Bu-Pip-phos) in combination with palladium salts provided active catalysts for the cross-coupling of aryl halides under mild conditions in aqueous solv...
Article
Sterically demanding, water-soluble alkylphosphines have been used in combination with various palladium salts in Suzuki, Sonogashira, and Heck couplings of aryl bromides under mild conditions in aqueous solvents. The tert-butyl-substituted ligands 2-(di-tert-butylphosphino)ethyltrimethylammonium chloride (t-Bu-Amphos) and 4-(di-tert-butylphosphino...
Article
[reaction: see text] Sterically demanding, sulfonated arylphosphines TXPTS and TMAPTS have been applied to the aqueous-phase Heck and Suzuki coupling of aryl bromides. TXPTS provides good yields of Heck coupling products from aryl bromides at 80 degrees C, while both TMAPTS and TPPTS gave significantly less active catalysts. TXPTS is the first liga...
Article
Carcinogenic aryl hydrazines produce C8-arylated purine adducts. The effect of these adducts on DNA conformation and their role in hydrazine carcinogenesis are unknown. Here, we describe a new synthetic route to produce these adducts that is also compatible with the synthesis of the corresponding phosphoramidites needed for oligonucleotide synthesi...
Article
Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'...
Conference Paper
Increased polymerization yield is observed in the copolymerization of styrene and CO in ionic liquids (ILs) compared to commonly used molecular solvents using palladium catalysts. Conditions for the copolymerizations were optimized and the effect of changes in the cation and anion of the IL solvent were determined. These results suggest that polar,...
Article
Increased polymerization yield is observed in the copolymerization of styrene and CO in ionic liquids (ILs) compared to commonly used molecular solvents using palladium catalysts. Conditions for the copolymerizations were optimized and the effect of changes in the cation and anion of the IL solvent were determined. These results suggest that polar,...
Article
The palladium-catalyzed copolymerization of styrene and CO in an ionic liquid solvent, 1-hexylpyridinium bis(trifluoromethanesulfonyl)imide, gave improved yields and increased molecular weights compared to polymerizations run in methanol.
Article
[reaction: see text]. Sterically demanding, water-soluble alkylphosphines have been found to give highly active catalysts for Suzuki coupling of aryl bromides in aqueous solvents. A variety of aryl bromides and boronic acids were coupled in excellent yield. Turnover numbers up to 734 000 mmol/mmol Pd have been achieved under mild conditions.
Article
The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and P(t-Bu)(3) in a 1:1 ratio, and the reactions of aryl chlorides occur at room temperature or 70 degrees C. The arylation of indoles and the new arylation of carbamates also occur when using P(t-Bu)(3) as ligand.