Synthesis of 3,6-dichloro salicylic acid by Kolbe–Schmitt reaction. 2. Proton transfer mechanism for the side reaction

Experimental and computational efforts were combined to clarify the primary reason for the low yield of 3,6-dichloro salicylic acid synthesized from 2,5-dichloro phenoxide and CO₂ by the Kolbe–Schmitt reaction. Liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS) analysis showed that di-potassium salt is the unique ionized existing form of 3,6-dichloro salicylate as the direct carboxylate product. In addition, a byproduct 2,5-DCP with equivalent 3,6-dichloro salicylate is also produced. Theoretical investigation by means of the density functional theory revealed that the formation of 2,5-DCP can easily occur through a Brønsted–Lowry proton transfer mechanism, which is characterized by the rotation of carboxyl with a favorable thermodynamic potential. The byproduct 2,5-DCP can reach 50 % in a maximum theoretical yield, which will seriously inhibit the positive reaction equilibrium, meanwhile it deteriorates the mass transfer due to its high viscosity. This side reaction is confirmed to be the controlling factor for the low yield of 3,6-DCSA.     

Enantioselective hydrogen atom transfer to α-sulfonyl radicals controlled by selective coordination of a chiral Lewis acid to an enantiotopic sulfonyl oxygen

Enantioselective hydrogen atom transfer to α-sulfonyl radicals generated from the alkyl radical addition to 2-propenyl and 1-phenylethenyl sulfones in the presence of chiral Lewis acids affords products with high enantioselectivity. The stereochemical course is discussed with the transition states involving selective coordination of a chiral Lewis acid to an enantiotopic sulfonyl oxygen.     

The mechanism of efficient asymmetric transfer hydrogenation of acetophenone using an iron(II) complex containing an (S,S)-Ph2PCH2CH═NCHPhCHPhN═CHCH2PPh2 ligand: partial ligand reduction is the key

On the basis of a kinetic study and other evidence, we propose a mechanism of activation and operation of a highly active system generated from the precatalyst trans-[Fe(CO)(Br)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-N═CHCH(2)PPh(2))][BPh(4)] (2) for the asymmetric transfer hydrogenation of acetophenone in basic isopropanol. An induction period for catalyst activation is observed before the catalytic production of 1-phenethanol. The activation step is proposed to involve a rapid reaction of 2 with excess base to give an ene-amido complex [Fe(CO)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-NCH═CHPPh(2))](+) (Fe(p)) and a bis(enamido) complex Fe(CO)(Ph(2)PCH═CH-N-(S,S-CH(Ph)CH(Ph))-N-CH═CHPPh(2)) (5); 5 was partially characterized. The slow step in the catalyst activation is thought to be the reaction of Fe(p) with isopropoxide to give the catalytically active amido-(ene-amido) complex Fe(a) with a half-reduced, deprotonated PNNP ligand. This can be trapped by reaction with HCl in ether to give, after isolation with NaBPh(4), [Fe(CO)(Cl)(Ph(2)PCH(2)CH(2)N(H)-((S,S)-CH(Ph)CH(Ph))-N═CHCH(2)PPh(2))][BPh(4)] (7) which was characterized using multinuclear NMR and high-resolution mass spectrometry. When compound 7 is treated with base, it directly enters the catalytic cycle with no induction period. A precatalyst with the fully reduced P-NH-NH-P ligand was prepared and characterized by single crystal X-ray diffraction. It was found to be much less active than 2 or 7. Reaction profiles obtained by varying the initial concentrations of acetophenone, precatalyst, base, and acetone and by varying the temperature were fit to the kinetic model corresponding to the proposed mechanism by numerical simulation to obtain a unique set of rate constants and thermodynamic parameters.