Bicyclobutane

Bicyclo[1.1.0]butane 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 &mdash; its strain energy is estimated at 63.9 kcal mol&minus;1. It is a nonplanar molecule, with a dihedral angle between the two cyclopropane rings of 123°.

The first reported bicyclobutane was the ethyl carboxylate 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:
 * Wurtz-reaction Bicyclobutane synthesis.svg

A synthetic approach to bicyclobutane derivatives involves ring closure of a suitably substituted 2-bromo-1-(chloromethyl)cyclopropane with magnesium in THF. 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. Bicyclo[1.1.0]butanes are explored in medicinal chemistry as covalent reactive groups.
 * [[File:SchemeBCBs.svg|center|frameless|582x582px|Bicyclo[1.1.1]pentanes to Bicyclo[1.1.0]butanes]]

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

Biological synthesis
Linolenic acid can be converted into its bicyclobutane derivative using a fusion protein produced by a strain of the cyanobacterium Anabaena sphaerica (strain PCC 7120). The other group reported a directed evolution approach, whereby engineered heme protein was expressed in E. coli and optimized for rate and yield of a substituted bicyclobutane derivative.