Temperature-controlled regioselectivity in the reductive cleavage of p-methoxybenzylidene acetals.
The regioselective ring opening of pyranosidic 4,6-p-methoxybenzylidene acetals with BH(3)/Bu(2)BOTf in THF can be tuned by adjusting the reaction temperature and reagent concentrations. Reductive cleavage at 0 degrees C resulted in the exclusive formation of 4-O-p-methoxybenzyl (PMB) ethers, whereas reaction at -78 degrees C produced 6-O-PMB ethers in high yields. The latter condition was observed to be compatible with a variety of acid-sensitive functional groups, including allyl and enol ethers. The presence of water does not interfere with reductive ring opening and may contribute toward in situ generation of H(+) as a catalyst for 6-O-PMB ether formation. Reductive cleavage under rigorously aprotic conditions is greatly decelerated, and yields only the 4-O-PMB ether. The temperature-dependent reductive cleavage of the 4,6-acetal can be described in terms of kinetic versus thermodynamic control: Lewis-acid coordination of the more accessible O-6 is favored at higher temperatures, whereas protonation of the more basic but sterically encumbered O-4 predominates at low temperatures.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
Jesús M
JM
Hernández-Torres
Jihane
J
Achkar
Alexander
A
Wei
D000080:Acetals / Q000737:chemistry*; D001597:Benzylidene Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013696:Temperature
D000080:Acetals; D001597:Benzylidene Compounds