Carboxylic acids and their corresponding carboxylate anions are generally utilized as Brønsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael addition of BnONH to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Brønsted base through a benzoyloxy anion to activate the nucleophile. Moreover, molecular sieves were found to play an important role in generating the ternary borate complexes, which were crucial for obtaining high enantioselectivity as demonstrated by DFT calculations. We also designed a new thiourea catalyst for the intramolecular oxa-Michael addition to suppress another catalytic pathway via a binary borate complex using steric hindrance between the catalyst and substrate. Finally, to demonstrate the synthetic versatility of both hetero-Michael additions, we used them to accomplish the asymmetric synthesis of key intermediates in pharmaceutically important molecules, including sitagliptin and α-tocopherol.

The displacement reaction of various non-activated aryl halides with cyanide ions was investigated in the presence of palladium salts. Various aryl iodides and bromides were converted into the corresponding aryl cyanides in good yields under mild conditions. The addition of certain substances, such as potassium hydroxide and potassium carbonate, enhanced the catalytic activity. Hexamethylphosphoric triamide, in which potassium cyanide was scarcely soluble, was an outstanding solvent for the reaction. The reduced palladium species was supposed to be the active catalyst.

Tuning the organocatalyst: An unprecedented enantioselective intramolecular oxa-Michael reaction of unactivated α,β-unsaturated amides and esters catalyzed by a powerful hydrogen-bond-donating organocatalyst has been developed. Furthermore, the products obtained from this reaction have been used for the straightforward asymmetric synthesis of several natural products and biologically important compounds.

Differential thermal analysis, differential scanning calorimetry, and measurements of the

The nucleophilic displacement of iodobenzene with potassium cyanide was carried out in HMPA in the presence of palladium(II) acetate. The reaction obeys the following kinetics; d[C_6H_5CN]/dt=k[Pd(OAc)_2]_0(M_KCN)^2/3 A reaction scheme composed of two cycles has been proposed: in one cycle Pd0 activates iodobenzene and in the other cycle Pd2+ assists the dissolution of potassium cyanide.

The in situ-generated nickel(0) species, presumably atomic nickel, from nickel(II) salt and zinc powder has been proved to be an effective catalyst for the Finkelstein-type displacement reaction of aryl bromides with potassium iodide to give aryl iodides under mild conditions. This species was also effective for the Ullmann-type coupling of bromides or aryl iodides by the use of zinc powder to give biaryls. Furthermore, in the presence of excess nickel(II) salt, the coupling reaction proceeded smoothly, even at an ambient temperature, to give various biaryls in very good yields.

An asymmetric thia-Michael addition of arylthiols to α,β-unsaturated carboxylic acids using a thiourea catalyst that bears arylboronic acid and tertiary amine moieties is reported.

Facile synthesis of aryl iodides from aryl halides was reported. NiBr2–Zn catalyzed the halogen exchange reaction of aryl bromides with potassium iodide under mild conditions. At elevated temperatures, NiBr2–PBu3 was an effective catalyst.