Recent Synthetic Developments of Asymmetric Multicomponent Transformations: Strecker, Mannich, Passerini and Ugi Reactions

Multicomponent reactions (MCRs) are important transformations, which allow the attainment of structurally complex derivatives in a single step, starting from three or more compounds with relatively simple structures. These reactions are generally associated with the principles of green chemistry, allowing the incorporation of most (or all) atoms of the starting materials in the products (atom economy) and reducing purification steps (and, consequently, the need for solvents and waste production). For a long time, asymmetric methodologies (in special enantioselective protocols) for most multicomponent transformations remained a gap in the literature, limiting the use of these reactions to produce derivatives only as racemates or in low diastereoselectivities. Over the last two decades, a better comprehension of the mechanisms associated with these transformations allowed the development of efficient enantio- and diastereoselective procedures, attracting the interest of both academia and industry. In this review, selected examples of four important multicomponent reactions (Strecker, Mannich, Passerini and Ugi) will be discussed, presenting a general overview of the development of this field and pointing out possible advantages and limitations of the above mentioned methodologies. In some cases, discussions around mechanisms, proposed transition states and activation modes will be detailed disclosed.