Synthesis of 2-Substituted Cyclobutanones by a Suzuki Reaction and Dephosphorylation Sequence

We report a novel process for the preparation of 2-substituted cyclobutanones. Such a method relies on the cross-coupling reaction of bromocyclobutenyl diethyl phosphate with either boronic acids or organozinc reagents. Dephosphorylation of the prepared 2-substituted cyclobutenyl phosphates affords 2-substituted cyclobutanones. We observed that the course of the dephosphorylation reaction depends on the properties of the substituents found on the cyclobutene nucleus. The presence of groups capable of stabilizing the negative charge is necessary for ring opening of cyclobutanones. The scope of the reported process for the preparation of 2-substituted cyclobutanones has also been extended to the preparation of cyclobutenyl sulfides.

Automated summary

A novel process for the preparation of 2-substituted cyclobutanones is reported, relying on a cross-coupling reaction and subsequent dephosphorylation. The course of the dephosphorylation reaction is observed to depend on the substituent properties on the cyclobutene nucleus. The method has been extended to the preparation of cyclobutenyl sulfides.