The synthesis of cyclic substrates via a tandem Michael- aldol or tandem Michael-Michael process has been achieved using tri-n butylphosphine and toluene-4- thiol. A D-ribose derived unsaturated aldehyde can be cyclised in a tandem Michael-aldol fashion to a highly functionalised cyclopentane catalytically using a thiolate nucleophile. Symmetrical dienone substrates have been cyclised in a Michael-Michael fashion giving a single 5 or 6 membered carbocyclic product whereas an unsymmetrical bis-enone was cyclised to two isomeric 6 membered products. Dienoate systems have been established as unsuitable for cyclisation with phosphine and thiolate nucleophiles.
An unsymmetrical mono-enone mono-enoate substrate was cyclised using a phosphine nucleophile giving the product as a single isomer, whereas the thiolate nucleophile gave two products which were separable by chromatography.