Enantioselective solvent-free Robinson annulation reactions

The enantio selective cyclization of the prochiral cyclic substrates 1 to 7 and 26, can be carried out in the neat using S-proline as catalyst. The su bstrates 18 to 22 and 27 could not be cyclized with S-proline but could be cyclized with a mixture of S-phenylalanine and d-camphorsulphonic acid. The enantio selective cyclization of prochiral acyclic triones 45 and 47 and a lso the racemic tricarbonyl compounds 54 to 57 could also be carried out in the neat using S-proline as catalyst. The optically active enediones obtai ned in the above cyclizations could also be obtained directly from 1,3-dion es or 2-hydroxymethylene cycloalkanones in a one-pot reaction with methyl v inyl ketone (MVK) and S-proline in the absence of solvents. C-13 NMR studie s of the one-pot synthesis of S-11 and S-14 reveal that the annulations inv olve initial formation of an acid-base complex followed by a Michael reacti on and then an enantioselective cyclization, Such enantioselective cyclizat ions probably occur on the surface of S-proline crystals.