Lanthanum(III) catalysts for highly efficient and chemoselective transesterification

A facile, atom-economical, and chemoselective esterification is crucial in modern organic synthesis, particularly in the areas of pharmaceutical, polymer, and material science. However, a truly practical catalytic transesterification of carboxylic esters with various alcohols has not yet been well established, since, with many conventional catalysts, the substrates are limited to 1 degrees- and cyclic 2 degrees-alcohols. In sharp contrast, if we take advantage of the high catalytic activities of La(Oi-Pr)(3), La(OTf)(3), and La(NO3)(3) as ligand-free catalysts, ligand-assisted or additive-enhanced lanthanum(III) catalysts can be highly effective acid-base combined catalysts in transesterification. A highly active dinuclear La(III) catalyst, which is prepared in situ from lanthanum(III) isopropoxide and 2-(2-methoxyethoxy)ethanol, is effective for the practical transesterification of methyl carboxylates, ethyl acetate, weakly reactive dimethyl carbonate, and much less-reactive methyl carbamates with 1 degrees- and cyclic 2 degrees-alcohols. As the second generation, nearly neutral lanthanum(III) nitrate alkoxide'', namely La(OR)(m)(NO3)(3-m), has been developed. This catalyst is prepared in situ from inexpensive, stable, low-toxic lanthanum(III) nitrate hydrate and methyltrioctylphosphonium methyl carbonate, and is highly useful in the non-epimerized transesterification of alpha-substituted chiral carboxylic esters, even under azeotropic reflux conditions. In these practical La(III)-catalyzed transesterifications, colorless esters can be obtained in small-to large-scale synthesis without the need for inconvenient work-up or careful purification procedures.