Michael addition of indoles to nitroolefins in natural deep eutectic solvents

Natural deep eutectic solvents (NaDES) are easy to prepare, biodegradable and have low toxicity,¹ being used in the development of various types of reactions.^2,3 In this study, different combinations of NaDES based on L-menthol and L-proline, as hydrogen bond acceptor, were evaluated in the Michael addition reaction between indole 1 and nitrostyrene 2. Among the various conditions tested, the combination of L-proline:lactic acid (1:4), using microwave irradiation, proved to be the most promising, yielding the product 3 in 91% yield in only 45 min. The NaDES could be recycled 4 times without showing a significant decrease in yield. Compound 3 was then reduced, with the resulting amine 4 being used in the Ugi multicomponent reaction to obtain compound 5 in 43% yield.^4,5 The scope and limitation of this protocol is under investigation.