Palladium-catalyzed decarboxylative coupling of potassium nitrophenyl acetates with aryl halides

A palladium-catalyzed decarboxylative cross-coupling of potassium 2- and 4-nitrophenyl acetates with aryl chlorides and bromides has been developed. Because the nitro group can be readily converted to many other functional groups, the new reaction provides a useful method for the preparation of diverse 1,1-diaryl methanes and their derivatives.     

Photoinduced addition of phthalimide to unactivated alkynes

Photoexcited phthalimide in equilibrium with its conjugated base produces the regioselective hydrophthalimidation of conjugated alkynes. The vinylphthalimide thus obtained is hydrolyzed to the corresponding carbonyl compound. With unconjugated alkynes, the outcome is a double addition of phthalimide to the triple bond. The reaction is assumed to take place via single electron transfer from either the alkyne or the phthalimide anion to the excited phthalimide as the primary photoprocess.     

Gold-catalyzed 1,2-/1,2-bis-acetoxy migration of 1,4-bis-propargyl acetates: a mechanistic study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2-/1,2-bis-acetoxy migration in 1,4-bis-propargyl acetates to form 2,3-bis-acetoxy-1,3-dienes. In this way, (1Z,3Z)- or (1Z,3E)- and (1E,3Z)-1,3-dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one-pot synthesis of quinoxaline heterocycles and tandem Diels-Alder processes have also been devised.     

Alpha-glucosidase inhibitors with a phthalimide skeleton: structure-activity relationship study

Alpha-glucosidase inhibitors with a phthalimide skeleton were prepared. Structure-activity relationship studies indicated a critical role for the hydrophobicity of the substituent at the nitrogen atom of the phthalimide skeleton. Introduction of electron-withdrawing groups, including a nitro group and chlorine, influenced the activity. Optimization studies led us to design 4,5,6,7-tetrachloro-N-phenylphthalimide (CPOP) and its N-phenylalkyl derivatives. CP0P and 4,5,6,7-tetrachloro-N-(4-phenylbutyl)phthalimide (CP4P) proved to be more potent alpha-glucosidase inhibitors than the known inhibitor 1-deoxynojirimycin.     

Structure-reactivity correlation in the pyridinolysis of substituted phenyl acetates

The pyridinolysis of substituted phenyl acetates in acetonitrile was investigated with an electric conductivity method. The rates of these reactions were increased with electron-donating group in pyridine and electron-withdrawing group in phenyl acetate, ϱ_x (X;substituents in phenyl ring) values increase gradually according to the electron-donating ability in pyridine substituents, but the |ϱ_y|(Y;substituents in pyridine ring) values decrease with that of substituents. The β values increase with increasing electron-withdrawing ability of the substituents in the phenyl ring, it can be inferred that N---C bond formation increases progressively p-methyl to p-nitrophenyl acetates. This is in agreement with prediction of substituent effects for a simple S_N2 displacement reaction. The sensitivity parameters, β and ϱ, are inter-related and are themselves sensitive to the reactivity of the system. All above results are interpreted in terms of a dissociative S_N2 mechanism involving a metastable tetrahedral intermediate.     

Photoinduced fragmentation and rearrangement of phenyl substituted epoxyethylphosphonates

An alternative source to phosphonocarbenes is described using phosphorus substituted oxiranes as precursors which compliments the conventional diazo route to these transient species. The results are in accord with previous theories advanced to rationalize the mode of photocyclo-elimination of a variety of other unsymmetrically substituted oxiranes.     

Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.     

Photoinduced water splitting with oxotitanium porphyrin: a computational study

The photochemistry of the hydrogen-bonded oxotitanium porphyrin-water complex (TiOP-H(2)O) has been explored with electronic-structure calculations. It is shown that intramolecular charge-transfer processes, which are initiated by the excitation of the Soret band of TiOP, accumulate electronic charge on the oxygen atom of TiOP, which in turn abstracts a hydrogen atom from water by an exoenergetic and essentially barrierless hydrogen-transfer reaction, resulting in the TiPOH˙-OH˙ biradical. About 75% of the absorbed photon energy is thus stored as chemical energy in two ground-state radicals. Absorption of a second photon by TiPOH˙ can result in the detachment of the H˙ radical and recovery of the photocatalyzer TiOP. Again, about 75% of the photon energy is stored in the dissociation energy of TiPOH˙. Overall, a water molecule is decomposed into H˙ and OH˙ radicals by the absorption of two visible photons. Exoenergetic radical recombination reactions can yield molecular hydrogen, molecular oxygen or hydrogen peroxide as closed-shell products.     

Substituent effects on the mass spectra of substituted phenyl acetates

The mass spectra of a series of meta- and para-substituted phenyl acetates have been examined. Substituent effects have been correlated with Δ (AP-IP) values and by using the Harrison and Chin approach. The bond-cleavage and rearrangement reactions of phenyl accetates are compared with the corresponding reactions of acetanilides and the differences attributed to the degree of transmission of polar effects in the two systems.     

A mechanism of mass spectral ketene elimination from phenyl acetates

Deuterium labelling experiments show that mass spectal ketene elimination from O-acetyl methyl salicylate involves a four-membered cyclic transition state and gives a phenolic fragment ion.     

Copper-catalysed photoinduced decarboxylative alkynylation: a combined experimental and computational study

Redox-active esters (RAEs) as alkyl radical precursors have demonstrated great advantages for C–C bond formation. A decarboxylative cross-coupling method is described to afford substituted alkynes from various carboxylic acids using copper catalysts CuCl and Cu(acac)₂. The photoexcitation of copper acetylides with electron-rich NEt₃ as a ligand provides a general strategy to generate a range of alkyl radicals from RAEs of carboxylic acids, which can be readily coupled with a variety of aromatic alkynes. The scope of this cross-coupling reaction can be further expanded to aliphatic alkynes and alkynyl silanes using a catalytic amount of preformed copper-phenylacetylide. In addition, DFT calculations revealed the favorable reaction pathway and that the bidentate acetylacetonate ligand of the copper intermediate plays an important role in inhibiting the homo-coupling of the alkyne.

Redox-active esters (RAEs) as alkyl radical precursors have demonstrated great advantages for Cu-catalysed C–C bond formation.     

Substituent effects in the fragmentation reactions of acetanilides and phenyl acetates

The mass spectra of a group of m- and p-substituted acetanilides were measured to determine the effect of the substituents, if any, on the rate of C₂H₂O expulsion (rearrangement) vs. the rate of [CH₃CO]⁺ formation (simple cleavage). Our results agree with observations of others in that substituents which raise the ionization potential of the aromatic ring appear to localize, on the average, less charge density on this locus, and conversely. The atomic composition of the substituent, however, irrespective of its position, seems to determine the relative rates of the competing reaction. Although in several cases Z_m/Z_p values were close to unity, rearrangement of isomeric molecular ions to a common species is shown not to occur.     

Zirconium-catalyzed amine oxidation: a mechanistic study

The zirconium-catalyzed oxidation of amines in the presence of hydroperoxides gives the corresponding nitro compounds in high yields. In the present paper, we describe mechanistic details of this three-step oxidation, which was investigated by means of DFT calculations. It is shown that N-oxides, hydroxylamines, and nitroso derivatives are formed as intermediates. These compounds had already been postulated on the basis of synthetic experiments. During the oxidation process, the nitrogen atom changes its electronic character from a strong nucleophilic center to a moderate electrophilic center; this is reflected by the geometry of the transition states of the oxygen-transfer process.     

Formation of phosphaethyne dimers: a mechanistic study

High-level ab initio (CCSD(T), CBS-QB3 and CASSCF, CASPT2, MR-ACPF, MR-ACPF-2) and density functional theory (B3LYP) calculations were carried out to study the dimerization of phosphaacetylene or phosphaethyne (HCP). Seventeen low energy closed-shell and five open-shell phosphaacetylene dimers were found on the potential energy surface. Two head-to-head, one head-to-tail and three other dimerization reaction pathways were determined, all with high activation barriers, suggesting that closed-shell minima are usually kinetically stable. An open-shell head-to-head reaction pathway has also been found with moderate initial barrier (95.0 kJ mol(-1)) leading to 1,2- and 1,3-diphosphacyclobutadiene, suggesting that polymerization of HCP and oligomerization of its derivatives have open-shell mechanism. Formation of 1,2-diphosphacyclobutadiene is both thermodynamically and kinetically favored over 1,3-diphosphacyclobutadiene. A head-to-head reaction involving LiBr as a catalyst was also studied. It has been pointed out that LiBr catalyze the closed-shell mechanism. All the four possible reaction channels of this reaction yield 1,4-diphosphatriafulvene with a fairly low activation Gibbs-free energy (44.8 kJ mol(-1)), suggesting that this compound could be synthesized. This finding fully supports the experimental results.