Recent applications of thiourea-based organocatalysts in asymmetric multicomponent reactions (AMCRs)

Abstract

<p>This review describes the recent applications of thiourea-based organocatalysts in asymmetric multicomponent reactions.</p>

Non-Covalent Interactions in Enantioselective Organocatalysis: Theoretical and Mechanistic Studies of Reactions Mediated by Dual H-Bond Donors, Bifunctional Squaramides, Thioureas and Related Catalysts

“…Catalytic asymmetric versions of this reaction were known at the time but required either metal catalysis or strict reaction conditions. This reaction opened the way to intensive research, and soon after, this and other thioureabased bifunctional catalysts were applied in several reactions, e.g., the aza-Henry reaction, dynamic kinetic resolution of aza-lactones, Michael addition to α,β-unsaturated imides, the aldol reaction, sp 2 -alkylations, spiro-ketal formation and many others [1][2][3][4]. The authors showed through experiments using only either the amine or the thiourea as catalysts that for any significant amount of product 3 to be obtained and for high enantiomeric excesses to be achieved, the simultaneous presence of both units in the catalyst molecule was essential.…”

“…The activation of reactants by hydrogen bonding and other noncovalent interactions has enabled the development of an enormous variety of reactions in recent years, and consequently, the production of chiral substances for several applications. This was possible due to the discovery of an array of very efficient chiral bifunctional catalysts, mostly thiourea-or squaramide-based, usually combined with chiral amines or cinchona alkaloids, and more recently also amides, phosphines or sulfides [1][2][3][4]. Urea, thiosquaramide and even selenosquaramide chiral bifunctional catalysts are also starting to appear.…”

“…Squaramides are distinct from the ureas in their hydrogen bond donor and acceptor character since, upon hydrogen bond formation, aromaticity is enhanced in the latter. The cyclobutadienone ring contains two coplanar carbonyls and two NHs that are almost coplanar and essentially sp 2 hybridized so that the lone pairs are available for conjugation into the π-system orthogonal plane [6].…”

Recent Developments in Enantioselective Organocatalytic Cascade Reactions for the Construction of Halogenated Ring Systems

“…Cascade reactions are challenging to develop, which makes them even more interesting, since there is a need for careful consideration of reagent compatibility so that the desired chemoselectivity is reached. Organocatalysts are particularly useful for this purposes, because they may activate substrates or intermediates in more than one manner, allowing multiple reactions to take place in a domino sequence [27–31] …”

An Efficient and Practical Chemoenzymatic Route to (3R,3aR,6R,6aR)-Hexahydrofuro[3,2-b]furan-6-amino-3-ol (6-Aminoisomannide) from Renewable Sources

“…1 They are useful not only as chiral ligands, as in the enantioselective addition of dialkylzinc reagents to carbonyl compounds, 2,3 but also as precursors of other chiral derivatives used as ligands in metalcatalyzed enantioselective reactions 4,5 or as chiral organocatalysts. 6 Most chiral amino alcohols are derived from natural compounds, such as carbohydrates or amino acids, which are readily available enantiopure sources and possess suitable stereochemical features for good asymmetric induction. In particular, the manipulation of the chiral pool available from biomass, which appears very attractive for the synthesis of asymmetric auxiliaries 7 and organocatalysts, 8 could represent a simple and economical way to ob-tain chiral amino alcohols endowed with interesting stereochemical features.…”