Solid-Phase Synthesis of a Spiro[5.5]ketal

Significance

The solid-phase construction of a spiro[5.5]ketal library was described. Wang resin 1 was converted into the corresponding trichloroacetimidate, which was subjected to nucleophilic substitution by alcohol 2 to give immobilized alkene 3 (Step I). Alkene 3 was converted into aldehyde 4 by ozonolysis and reductive work-up with triphenylphosphine (Step II). Treatment of aldehyde 4 with alkyne 5 under basic conditions gave an alkyne carbinol, which was oxidized with IBX to afford polymer-bound alkynone 6 (Step III). The acid-labile THP protecting group and the Wang resin support were cleaved and the double intermolecular conjugate addition to the alkynone was initiated. Spiroketal 7 was obtained as a single isomer (Step IV), which was converted into epimeric alcohols 8 and 9 (Step V). According to this method, polymer-bound aldehydes (analogous to 4) were combined with alkynes (analogous to 5) to yield 91 spiroacetals (analogous to 7) in 5-45%.