Soluble ionic liquids have recently been used as supports for catalyst/reagent immobilization and synthesis in homogeneous solution phase. The wide range of ionic liquid supports available makes their use as supports compatible with most common chemistries. The solubility properties of these ionic liquid supports can be tuned by the variation of cations and anions to make them phase separate from less polar organic solvents and aqueous media. The ionic-liquid-supported species can therefore be purified from the reaction mixture by simple washings. Ionic-liquid-supported catalysts and reagents have been prepared and used, and they are easily recovered and reused. Parallel and combinatorial libraries of small molecules have been synthesized. Ionic-liquid-supported synthesis (ILSS) has been applied to the preparation of oligopeptides and oligosaccharides. The comparison of ILSS with solid-phase synthesis, soluble-polymer-supported synthesis, and fluorous phase synthesis has been highlighted where applicable.

Ionic-liquid-anchored (2S,4R)-4-hydroxyproline 12 catalyzes direct asymmetric aldol reactions with comparable enantioselectivities in DMSO, and with superior enantioselectivities in neat acetone or 2-butanone, than (S)-proline (8) (up to 28 % ee difference) itself. Furthermore, the supported catalyst 12 can be easily recycled and reused for at least four times without significant loss of yields and enantioselectivity.

A new strategy for the synthesis of oligopeptides was developed using an ionic liquid as a soluble support. The efficiency of this ionic liquid-phase approach was demonstrated by the synthesis of a bioactive pentapeptide, Leu(5)-enkephalin, in good yield and reasonable purity. The structures and purities of the reaction intermediates in each step were verified easily by routine spectroscopic analysis, and no chromatographic procedures were needed during the synthesis.

The efficiency of ionic liquid supported synthesis was demonstrated by the Suzuki reaction of ionic liquid supported iodobenzoate compounds with arylboronic acids in aqueous media to give, after cleavage with ammonia/methanol, biaryl products in good yields and high purities, without the need for chromatographic purification. [reaction: see text]