Ligand hydroxylation

We have disclosed that the ligands 4c, 10, and 77, when complexed with a metal ion such as Zn2 +, Ni2+, or Co2+, become highly active toward the hydrolysis of p-nitrophenyl picolinate (7). The catalysis is most likely to occur through formation of a ternary complex in the transition state or in reactive intermediates. The metal ion in such a complex serves to activate the ligand hydroxyl group for nucleophilic attack and to orient the substrate into a favorable position to undergo the reaction. 

Becker, M., Schindler, S., Karlin, K. D., etal., Intramolecular ligand hydroxylation Mechanistic high-pressure studies on the reaction of a dinuclear copper complex with dioxygen. Inorg. Chem. 1999, 38, 1989-1995. 

As already mentioned in Section II.C, the complexes [Cu2(R—XYL—H)]2+ (10) react with dioxygen, forming a kinetically describable intermediate dioxygen complex [Cu2(R—XYL—H)(02)]2+ (11), and attack by the peroxo group causes ligand hydroxylation to give the phenoxo and hydroxo-bridged complex [Cu2(R—XYL—0—)—(OH)]2+ (12). Here, we focus on the hydroxylation event, as described by the rate constant k2 (Scheme 13). 

Rg. 1.24 Key interactions between the active enantiomer BMS270394 and RAR-y. A key interaction involves a hydrogen bond between the ligand hydroxyl group and the sulfur of Met-272. Notice that the linking amide group makes complementary interactions with the enzyme. 

Phenylboronic acid forms a 1 1 complex with lactic acid in which the ligand hydroxyl proton is replaced by B.208 The stability constant of the species is (3.7 0.4) x 10 3. The fully protonated lactic acid reacts with a rate constant of 1401 mol1 s 1 ( 10%), while the acid anion gives a rate constant of 15001 mol-1 s 1 ( 10%). 

Karlin and co-workers have developed an aromatic ligand hydroxylation by O2 using a dinuclear copper(I) complex sujmorted by XYL (Scheme 3, where R = R = H), where a... 

An aliphatic ligand hydroxylation also proceeds upon decomposition of the (ji-rfirf -peToxo) dicopper(II) complex supported by Mechanistic studies indicated that the real active... 

Scheme 5. Reversible oxygenation of xylyl dicopper(I) complexes with pyridine arms and mechanism of ligand hydroxylation and copper mediated NIH shift (1,2-migration) reactions.

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