Thierry Ollevier and Etienne Nadeau from Université Laval, Canada show how bismuth (III) triflate is used as a mild and versatile catalyst for the synthesis of beta-amino esters and ketones. Ollevier reveals more about his work in the interview below.

1. Please explain, for a non-specialist, the significance of your article. 

The use of bismuth in organic synthesis has only recently been recognized and the uniqueness and outstanding potential of bismuth as a reagent or catalyst for organic transformations was revealed. Indeed, practically, the very low toxicity of bismuth derivatives permits their use in pharmaceutical and cosmetic industries. In the last decade, bismuth(III) salts have proved to be efficient and green catalysts for various organic reactions. Some of the major advantages of bismuth(III) salts are their low price, low toxicity and environmentally benign character. In this context, we developed a bismuth triflate-catalysed three-component Mannich-type reaction. This multi-component reaction allows a quick access to -amino carbonyl compounds which are of prime importance in the synthesis of biologically active molecules. In one single step, two reactions occur successively to give the expected product in very good yield. This method allows a quick and efficient access to a vast repertoire of -amino ketones and -amino esters. 

2. What has motivated you to conduct this work? 

We wish to explore the catalytic effects of bismuth(III) salts because bismuth is a cheap and non-toxic element. In this respect, we have been interested in the opportunity of taking advantage of bismuth-derived catalysts that are easy to handle and sufficiently Lewis acidic. Our method offers several advantages including mild reaction conditions, highly catalytic process and no formation of by-products. The conditions are suitable for a variety of aldehydes, aromatic amines and silyl enolates. Also, the practical use of Bi(OTf)₃ is highly valuable as a surrogate for HOTf. Because of its numerous benefits, this method for the one-pot synthesis of -amino esters and ketones using Bi(OTf)₃ catalysis should find utility in the synthesis of biologically active compounds. 

3. Where do you see this work developing in the future? 

One objective will be to develop catalysts that will enable the Mannich reaction to be performed in aqueous media. One of the other major challenges will be to develop new chiral bismuth(III) derived catalysts enabling efficient asymmetric synthesis for reactions of synthetic importance, e.g., for the Mannich reaction. This reaction is a major incentive for the development of more efficient and selective new Lewis and Brønsted catalysts. 

4. Are there any particular challenges facing future research in this area? 

The usefulness of bismuth(III) salts in organic synthesis is now well established. Very recently, we have contributed to the emergence of catalytic asymmetric reactions using bismuth(III) salts showing that a whole new horizon of challenges lies ahead for this research area. In particular, the use of chiral basic ligands leading to new types of water-compatible chiral Lewis Acids could enable a wide range of asymmetric catalysis in aqueous media. The development of new catalytic systems will open the door to new applications of Lewis Acids in synthetic organic chemistry.