New Reactions of -Halocarbanions: Simple Synthesis of Substituted Tetrahydrofurans

The treatment of 4-chlorobutyronitrile, 3-chloropropyl phenyl sulfone, and other related compounds with a base afforded gamma-halocarbanions that undergo fast intramolecular substitution of the halogen to produce substituted cyclopropanes. We found that these short-lived carbanionic intermediates can be trapped with active external electrophilic partners, such as aldehydes, to give the aldol anions. These anions then undergo rapid intramolecular substitution of chloride to produce 2,3-disubstituted tetrahydrofurans. Under the right conditions, yields of tetrahydrofurans are excellent. Similar reactions with ketones gives 2,2,3-trisubstituted furans, but this process is usually less efficient. Ratios between the rates of intramolecular and intermolecular processes were qualitatively estimated by competitive experiments. It was shown that gamma-halo and gamma-trimethylammonium substituents substantially increase the kinetic CH acidity of alkane nitriles and sulfones.