Cyclobutenone was originally synthesized from the 3-bromocyclobutanone and 3-chlorocyclobutanone precursors which were prepared from an allene and a ketene via two independent routes. Scheme 7 shows the preparation from cyclobutenone from an allene.
Activated alkyoxyacetylenes can be synthesized in a single-pot preparation of triisopropylsilyloxyacetylenes from esters. The silyloxyacetylenes are useful substitutes for alkoxyacetylenes in [2 + 2] cycloaddition reactions with ketenes and vinylketenes affording cyclobutenones (Scheme 8).
Diazoketones can be synthesized in one-step from readily available ketones or carboxylic acid precursors by the addition of diazomethane to acyl chlorides. A diazo group transfer method can be used to produce α,β-unsaturated ketones. The traditional method of the deformylative diazo transfer approach has been improved upon by substituting the trifluoroacetylation of generated lithium enolates for the Claisen formylation step. The key step in this procedure is activation of the ketone starting material to the corresponding α-trifluoroacetyl derivative using trifluoroethyltrifluoroacetate (TFEA) (Scheme 9).
Alkynes or ketenophiles can be synthesized by various methods. Trialkylsilyloxyalkynes have proven to be excellent ketenophiles. These alkynes react in the annulation reaction to form resorcinol monosilyl ethers which can be de-protected under mild reaction conditions.
Base-promoted dehydrohalogenation of (Z)-2-halovinyl ethers to form alkoxyacetylenes is one of the most well established routes of alkyne synthesis (Scheme 10).
The synthesized alkynes are then heated in benzene or toluene in presence of excess cyclobutenone initiating the benzannulation reaction. Treatment with n-BuNF in tetrahydrofuran removes the siloxy groups to form the desired diols.