Air-stable, storable, and highly efficient chiral zirconium catalysts for enantioselective Mannich-type, aza Diels–Alder, aldol, and hetero Diels–Alder reactions

For the synthesis of optically active compounds, chiral catalysts have attracted much attention because large quantities of optically active molecules can be prepared from a small amount of a chiral source. However, many chiral catalysts are often unstable in air (oxygen) and/or in the presence of water. This is especially the case in chiral Lewis acid catalysis, because most Lewis acids are air- and moisture-sensitive. Therefore, many catalysts are prepared in situ in an appropriate solvent just before use, and they cannot be stored for extended periods. We have developed air-stable, storable, and highly efficient chiral zirconium Lewis acids. The catalysts promoted asymmetric Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions efficiently with high enantioselectivities. A key to stabilizing the catalysts is an appropriate combination of chiral zirconium Lewis acids with molecular sieves, and the zirconium-molecular sieves-combined catalysts can be stored for extended periods in air at room temperature without loss of activity. Moreover, it has been demonstrated that the catalysts can be recovered and reused.