Bicyclobutane


Bicyclobutane is an organic compound with the formula C4H6. It is a bicyclic molecule consisting of two cis-fused cyclopropane rings, and is a colorless and easily condensed gas. Bicyclobutane is noted for being one of the most strained compounds that is isolatable on a large scale — 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°.
The first reported bicyclobutane was the carboxyethyl derivative, C4H5CO2Et, which was prepared by dehydrohalogenation the corresponding bromocyclobutanecarboxylate ester with sodium hydride. The parent hydrocarbon was prepared from 1-bromo-3-chlorocyclobutane by conversion of the bromocyclobutanecarboxylate ester, followed by intramolecular Wurtz coupling using molten sodium. The intermediate 1-bromo-3-chlorocyclobutane can also be prepared via a modified Hunsdiecker reaction from 3-chlorocyclobutanecarboxylic acid using mercuric oxide and bromine:
A synthetic approach to bicyclobutane derivatives involves ring closure of a suitably substituted 2-bromo-1-cyclopropane with magnesium in THF.
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.

Biological synthesis

Multiple research groups have reported success in synthesizing bicyclobutane-containing molecules using enzymes in living cells. One group reported the transformation of linolenic acid into a bicyclobutane fatty acid via a protein produced by a strain of the cyanobacterium Anabaena sp.. The other group reported a directed evolution approach, whereby engineered heme protein was expressed in E. coli and successfully optimized for increased rate and yield of biosynthesis of a substituted bicyclobutane derivative.