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The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium-catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond-cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon-based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C−H bond.

Tris(pentafluorophenyl)borane, B(C6F5)3, has been found to be an effective catalyst to access the hydridoborate anion, [N(CH2CH2CH2)3Sn][HB(C6F5)3], via hydride abstraction from the hypercoordinated tin reagent, iPr-tricarbastannatrane. This process has been applied to the B(C6F5)3-catalyzed transfer 1,4-hydrostannylation of electron-deficient olefins, namely benzylidene barbituric acids. Insights into the mechanism have been obtained via a series of 1H, 2H, 11B, 13C, and 119Sn NMR spectroscopy, mass spectrometry, and labeling experiments.

It is generally assumed that molecules behave ergodically during chemical reactions, that is, reactivities depend only on the total energy content and not on the initial state of the molecule. While there are a few examples of nonergodic behavior in small (usually electronically excited) species, to date there have been no reports of such behavior in larger covalently bound species composed of several tens of atoms. Here, we demonstrate vibrational mode-selective behavior in a series of palladium catalysts. When we excite solvent-tagged gas-phase Pd catalysts with an infrared laser that is tuned to be resonant with specific molecular vibrations, depending on which vibration we excite, we can select different reaction pathways. We also demonstrate that this behavior can be “turned off” via chemical substitution.

The asymmetric formation of all-carbon quaternary benzylic stereocenters containing a methyl substituent was realized by the enantioselective copper-catalyzed 1,4-addition of dimethylzinc to alkylidene Meldrum's acids in the presence of a chiral phosphoramidite. Copper source and ligand optimization studies are presented, as well as the scope and limitations of dimethylzinc addition to various alkylidene Meldrum's acids. Good to excellent yields and enantioselectivities were obtained.

A full account of the Pd-catalyzed intramolecular reactions of (E)-2,2-disubstituted 1-alkenyldimethylalanes with aryl triflates as an entry into polycarbocyclic structures displaying an ethyl−methyl-substituted all-carbon benzylic quaternary center is herein presented. It was found that the efficiency of the Pd-catalyzed carbon−carbon bond forming process is highly affected by the structure of the starting material, including tether length and aryl substitution pattern; substituting the position ortho to the triflate is mandatory to obtain a good yield of the carbocycle. Moreover, the formation of 1-ethyl-1-methylindanes is facile in comparison to the case for the analogous tetrahydronaphthalenes, for which the competing methyl cross-coupling reaction is equally competent. It was established through labeling studies that the carbon−carbon bond forming events are stereospecific and proceed though the intermediacy of a neopentylic sp3-gem-dimetallic palladio(II) dialkylaluminoalkane species, from which a 1...

Persistent intramolecular interactions between acidic C-H hydrogens and a variety of acceptors (X) (X = O, S, Br, Cl, and F) in solution were probed by (1)H NMR experiments, using 5-benzyl Meldrum's acid derivatives. To bring about formation of intramolecular C-H...X bonding, ortho-substituted benzyl Meldrum's acids were designed, for which hydrogen bonding occurred through a six-membered ring. Introduction of substituents on the aromatic moiety and in the tether allowed variation of electronic and steric factors. The superior acidity of Meldrum's acids impacted the ability of the C-H hydrogen to engage in nonclassical C-H...X bonds and drove the conformational properties of benzyl Meldrum's acid, in combination with steric factors, namely A(1,3)-allylic strain. Further understanding of intramolecular C-H...X bonds was gained by characterization of benzyl Meldrum's acids in the solid state, by X-ray analysis, and by the conformation correlated to the observations made in solution.

The ability to tune the reactivity of palladium carbenes derived from diphenylketene, which is dependent on the oxidation state of the metal center, is presented. Competition experiments illustrated that Pd(0) catalysts favor direct C−H functionalization of terminal alkynes and that Pd(II) catalysts lead to cyclopropanation of strained alkenes. In addition, a PdCl2-catalyzed cyclopropane isomerization of diphenylcyclopropanes and an unprecedented Pd(II)-catalyzed domino cyclopropanation/isomerization reaction are described.

The ambiphilic vinylcarbenoid reactivity of (α-(tributylstannyl)-π-allyl)palladium(II) species is demonstrated by the reaction of acetoxystannanes with Pd(dba)2, which promotes electrophilic metal−carbene reactions such as dimerization and cyclopropanation of strained alkenes. On the other hand, Pd(PPh3)4 and dppe revealed the nucleophilic nature of the dimetallic intermediates through sequential reactions of the carbon−metal bonds with dimethyl malonate.

[13444-94-5] PdBr2 (MW 266.23) InChI = 1S/2BrH.Pd/h2*1H;/q;;+2/p-2 InChIKey = INIOZDBICVTGEO-UHFFFAOYSA-L (used as an oxidizing agent; used as a Pd(II) catalyst; used as a source of Pd(0) precatalyst) Alternate Names: palladium bromide; palladium dibromide. Physical Data: mp 717 ± 2 °C1; X-ray structure.2 Solubility: soluble in HBr; insoluble in H2O.1 Form Supplied in: commercially available as a dark brown powder. Analysis of Reagent Purity: elemental analysis.3 Preparative Methods: palladium metal with HNO3 and HBr,1, 4 electrosynthesis from palladium metal and HBr,3 and by palladium metal with Br2 at high temperature.1 Handling, Storage, and Precautions: air stable; not hygroscopic.1

Lewis acid promoted substitution reactions employing Meldrum's acid and 5-methyl Meldrum's acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic C(sp(3))-C(sp(3)) bonds into C(sp(3))-X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically90%).

The reaction proceeds best when catalyzed by Rh2((S)-MEPY)4 but it delivers racemic products.

The reaction proceeds best when catalyzed by Rh2((S)-MEPY)4 but it delivers racemic products.

A systematic study outlining the enantioselective 1,4-addition of dialkylzinc reagents to 5-(1-arylalkylidene) and indenylidene Meldrum’s acids is presented. Variation of the aryl and alkyl groups present on the alkylidene was thoroughly explored. The 1,4-addition displayed compatibility with a wide range of heteroaromatics and functional groups, and the arene pattern of substitution affected enantioselection, with a para-substituted aryl group consistently leading to high enantioselectivities. The nature of the organozinc reagent on the efficiency and selectivity of the conjugate addition was also investigated. The solid-state conformation was determined for a number of alkylidene Meldrum’s acids and correlated with the observed enantioselectivity in relation to the arene pattern of substitution.

The enantioselective alkynylation of benzylidene Meldrum’s acids has been successfully achieved through rhodium-catalyzed addition of TMS-acetylene in the presence of bisphosphine ligand 3,5-Xylyl-MeOBIPHEP. The resulting Meldrum’s acids were obtained in good yields and up to 99% enantiomeric excess. The alkynylation method is carried out under mild reactions conditions and is compatible with an array of functional groups.

The enantioselective alkynylation of benzylidene Meldrum’s acids has been successfully achieved through rhodium-catalyzed addition of TMS-acetylene in the presence of bisphosphine ligand 3,5-Xylyl-MeOBIPHEP. The resulting Meldrum’s acids were obtained in good yields and up to 99% enantiomeric excess. The alkynylation method is carried out under mild reactions conditions and is compatible with an array of functional groups.

The modification of sp(3)-hybridized carbon centers through Pd-catalyzed reductive cleavage of unstrained carbon-carbon sigma bonds is described. From the hydrogenolysis of benzyl Meldrum's acids bearing an all-carbon benzylic quaternary center, Meldrum's acid and aromatics substituted with a tertiary benzylic stereocenter were obtained in good to excellent yields. Mechanistic studies showed that the reductive cleavage of enantioenriched benzylic quaternary centers proceeded with inversion of configuration, supporting a "loose" S(N)2 pathway.

A one-pot, two-step process that transforms terminal alkynes into ethyl methyl-substituted benzylic quaternary carbon centers is described. (E)-2,2-Disubstituted-1-alkenyldimethylalanes have been shown to participate in 1,2-alkyl migration from aluminum to carbon with concomitant arylation at the 2-position to furnish ethyl methyl-substituted benzylic quaternary carbon centers, when reacted intramolecularly with aryl halides and triflates in the presence of a Pd(0) catalyst. The protocol is initiated with Cp2ZrCl2-catalyzed methylalumination of terminal alkynes followed by palladium-catalyzed intramolecular arylation of the resulting (E)-2,2-disubstituted-1-alkenyldimethylalanes, leading to 1,2-methyl shift from aluminum to carbon. In that sequence, a total of three new C−C single bonds are made, and two of the three alkyl groups on Me3Al transferred to the substrate on vicinal carbons. This method was applied to a variety of substrates, and the mechanism was investigated by deuterium-labeling experiments...

A one-pot, two-step process that transforms terminal alkynes into ethyl methyl-substituted benzylic quaternary carbon centers is described. (E)-2,2-Disubstituted-1-alkenyldimethylalanes have been shown to participate in 1,2-alkyl migration from aluminum to carbon with concomitant arylation at the 2-position to furnish ethyl methyl-substituted benzylic quaternary carbon centers, when reacted intramolecularly with aryl halides and triflates in the presence of a Pd(0) catalyst. The protocol is initiated with Cp2ZrCl2-catalyzed methylalumination of terminal alkynes followed by palladium-catalyzed intramolecular arylation of the resulting (E)-2,2-disubstituted-1-alkenyldimethylalanes, leading to 1,2-methyl shift from aluminum to carbon. In that sequence, a total of three new C-C single bonds are made, and two of the three alkyl groups on Me3Al transferred to the substrate on vicinal carbons. This method was applied to a variety of substrates, and the mechanism was investigated by deuterium-labeling experiments, which revealed that protodealumination of the final dialkylaluminum triflate or halide intermediates by CH3CN results in the formation of the fourth bond in the course of the transformation.