Quinodimethanes in Heterocyclic Compound Synthesis

The ease with which an ort/in-quinodimethane can be formed is related to the stability of the aromatic heterocycle from which it is derived and to the degree of double bond character between the ortho ring carbons. The first of these aspects can be nicely illustrated by comparing the thiophene 2,3-quinodimethane with its furan counterpart - the latter is more stable than the former - the thiophene-derived species has much more to lose in its formation from an aromatic thiophene (and much more to gain by reacting to regain that aromaticity) than does the latter. 

Three main strategies have been employed for the production of heterocyclic ortho-quinodimethanes a 1,4-elimination, the chelotropic loss of sulfur dioxide from a 2,5-dihydrothiophene 5,5-dioxide, and the electrocyclic ring opening of a cyclobuteno-heterocycle each of these is illustrated diagramatically below. 

The use of cyclobuteno-heterocycles is of course dependent on a convenient synthesis (for an example, see section 11.14.2.3), but when available, they are excellent precursors, only rather moderate heating being required for ring opening, as shown by the example below, in which the initial Diels-Alder aduct is aromatised by reaction with excess quinone.  

4-Eliminations have involved l,2-bis(bromomethyl)-heterocycles with hot sodium iodide, ort/io-(trimethylsilylmethyl) heterenemethylammonium salts, ort/io-(trimethylsilylmethyl) heterenecarbinol mesylates, each with a source of fluoride, and ort/io-(tri-n-butylstannylmethyl) heterenecarbinol acetates with a Lewis 

An extensively developed route involves loss of a proton from indol-3-ylcarboxaldehyde imines (or their pyrrolic counterparts ), following reaction with an acylating agent, as illustrated below.  

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