Squaramide Catalyzed Asymmetric Synthesis of Five‐ and Six‐Membered Rings

Abstract

Chiral analogues of squaramides have been fruitful in organocatalyzed asymmetric reactions over last decade. Alongside other H-bonding catalysts like ureas, thioureas: squaramides have been proved to be efficient asymmetric catalysts for the formation of acyclic and cyclic chiral molecules. A wide range of cyclic molecules bearing multiple functionalities and stereocenters have been synthesized by using several bifunctional squaramides as catalysts. These catalysts perform as base utilizing basic N atom in their chiral extension and help in stereoinduction by forming H-bonds with suitable H-bond acceptors. The present review focuses on assembling recent progresses of asymmetric synthesis of five and six membered rings promoted by squaramides. A handful of articles have been published by several research groups documenting asymmetric construction of five-and six-membered rings as part of interesting and complex molecular architectures. Different methodologies like conventional and formal cycloadditions or cascade reactions have been engineered through the assistance of chiral squaramides to fabricate the carbo-and heterocycles. This review also includes dual and cooperative catalytic system in which squaramide is one of the catalysts.

Squaramide-Tethered Sulfonamides and Coumarins: Synthesis, Inhibition of Tumor-Associated CAs IX and XII and Docking Simulations

“…This is the reason for starting the synthesis with anilines 3 in Scheme 1, or with aminobenzenesulfonamides 7 and 9 in Scheme 2. 13 C-NMR supported the proposed structures; thus, resonances at roughly 180-184 ppm (assigned to C=O) and at 164-169 ppm (C-3 and C-4) are in agreement with reported squaramides bearing N,N′-diaryl or N-alkyl-N′-aryl substituents [55].…”

“…Data for 10: R f 0.2 (1:1 cyclohexane-EtOAc); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.98 (brs, 1H, NH), 7.81 (m, 1H, Ar-H), 7.56 (m, 3H, Ar-H), 7.41 (brs, 2H, SONH 2 ), 4.39 (brs, 3H, OMe) ppm; 13…”

“…was added and the reaction was kept at the same temperature for further 24 h. A precipitate was formed, which was filtered and washed with cold MeOH. , Ar-H), 7.17 (m, 2H, Ar-H), 6.96-6.93 (m, 2H, Ar-H), 6.19 (brd, 1H, J H,CH3 = 0.7 Hz, H-3 ), 4.10 (t, 2H, J H,H = 6.0 Hz, OCH 2 ), 3.63 (brq, 2H, J H,H = J CH2,NH = 6.8 Hz, NCH 2 ), 2.38 (brs, 3H, CH 3 ), 1.79 (quint, 2H, J H,H = 6.8 Hz, CH2), 1.65 (quint, 2H, J H,H = 6.9 Hz, CH 2 ), 1.49 (quint, 2H, J H,H = 6.7 Hz, CH 2 ) ppm; 13…”

“…Squaramides are currently gaining great attention and have found a myriad of applications [ 3 ] in diverse fields like: molecular sensors [ 4 ], including ion pair receptors [ 5 , 6 ], metal-organic frameworks (MOFs, due to their self-assembly properties) [ 7 ], organocatalysis [ 8 ], including Henry [ 9 ], Mannich [ 10 ], and aldol [ 11 ] reactions, asymmetric fluorinations [ 12 ], and cycloadditions/cascade reactions [ 13 ] to furnish carbo- and heterocycles, and also within medicinal chemistry [ 14 ]. Interestingly, squaramides are currently considered as vinylogous amides with increased conformational restriction and have been used in the bio-isosteric replacement of frequent connectors in drug design, like (thio)ureas, guanidines, and cyanoguanidines [ 15 ].…”

Regiodivergent Organocatalytic Reactions

“…Chiral squaramide has been shown to successfully catalyze several reactions including Michael additions, and the Mannich, aza-Henry, and Strecker reactions. Moreover, these catalysts have successfully produced enantio-enriched products in single and domino/cascade reactions in various asymmetric organic transformations [168][169][170][171][172][173][174][175][176].…”