Introduction
Current environmental challenges and the longstanding need for chiral compounds pose new demands on organic syntheses. Effective syntheses of chiral compounds necessary for medicines, materials, or crop protection must fulfill, besides high stereoselectivity, stringent environmental criteria. Asymmetric organocatalyses offer great opportunities in the synthesis of important chiral compounds and at the same time enable implementation of green chemistry principles.
Various enantioselective organocatalytic reactions, such as Michael additions of aldehydes to nitroalkenes, aminoxylation, and hydrazination of aldehydes can be performed in aqueous media or under solventless conditions using a ball mill. We have found out that these reactions proceed with high yields and highly enantioselective. The solventless methodology also allows more effective catalysis using organocatalysts, which employ non-covalent interactions for activation. Chiral thioureas and squaramides proved to be more enantioselective catalysts for Michael additions and domino Mannich/fluorination reactions under solventless conditions than in solvents. The in-situ release of unstable alkyloxyacetaldehydes from acetals using acidic ionic liquids and microwave irradiation improved the organocatalytic synthesis of antiviral drug oseltamivir. Greener solvent alternatives, such as 2-methyltetrahydrofurane allow highly enantioselective warfarin synthesis.