Synthesis of Tetrahydropyrans through Formal [4+2] Cycloaddition

Significance

Although insertion reactions with cyclopropanes are well known in organic chemistry, analogous reactivity with cyclobutanes has remained largely overlooked. The authors describe a Lewis acid catalyzed reaction between cyclobutanes and aldehydes to yield substituted tetrahydropyrans in high diastereomeric purity. The reaction is further modified into a formally {[2+2]+2} one-pot process, which gives the products in a higher overall yield. In the future of this chemistry, chiral ligands can potentially be applied to yield enantiopure products.