Bicyclobutane

Bicyclobutane is highly strained — its strain energy is estimated at 63.9 kcal mol⁻¹. It is a nonplanar molecule, with a dihedral angle between the two cyclopropane rings of 123°.^[2]

The first reported bicyclobutane was the ethyl carboxylate derivative, C₄H₅CO₂Et, which was prepared by dehydrohalogenation the corresponding bromocyclobutanecarboxylate ester with sodium hydride.^[2] The parent hydrocarbon was prepared from 1-bromo-3-chlorocyclobutane by conversion of the bromocyclobutanecarboxylate ester,^[1] followed by intramolecular Wurtz coupling using molten sodium.^[3] The intermediate 1-bromo-3-chlorocyclobutane can also be prepared via a modified Hunsdiecker reaction from 3-chlorocyclobutanecarboxylic acid using mercuric oxide and bromine:^[4]

Stereochemical evidence indicates that bicyclobutane undergoes thermolysis to form 1,3-butadiene with an activation energy of 41 kcal mol⁻¹ via a concerted pericyclic mechanism (cycloelimination, [σ2s+σ2a]).^[5]

Bicyclo[1.1.0]butanes are explored in medicinal chemistry as covalent reactive groups.^[6]

In the simplest case, double cyclopropanation of acetylene with a copper catalyst gives a 1:1 mixture of cyclopropenes and symmetric bicyclobutanes.^[7] Other symmetric bicyclobutanes form from functionalization of benzvalene.^[8]

A synthetic approach to more substituted bicyclobutane derivatives involves ring closure of a suitably substituted 2-bromo-1-(chloromethyl)cyclopropane with magnesium in THF,^[9] or methyllithium in diethyl ether (lithium-halogen exchange).^[10]

Substituted bicyclo[1.1.0]butanes can also be prepared from the reaction of iodo-bicyclo[1.1.1]pentanes with amines, thiols, and sulfinate salts:^[11]