Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ‐Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones

Abstract

Although acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea‐ammonium hybrid catalyst was shown to promote the O‐alkylation of enols with a racemic γ‐chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen‐bonding interactions between the chlorine atom of the γ‐chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst–substrate interactions, are crucial for achieving high stereoselectivity.

Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides, Nitroalkanes, Nitroalkenes, Esters, Heterocycles, Ketones and Fluoroamides

“…However, over the last five years, several groups have started to systematically investigate the introduction of alternative H‐bonding donors, i.e. ureas and thioureas to obtain new classes of highly active bifunctional ammonium salt catalysts [66–75] . Chiral back‐bones were derived from the natural chiral pool like Cinchona alkaloids; [66–70] amino acids; [71–73] or from easily available chiral diamines, i.e.…”

“…ureas and thioureas to obtain new classes of highly active bifunctional ammonium salt catalysts. [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ] Chiral back‐bones were derived from the natural chiral pool like Cinchona alkaloids;[ 66 , 67 , 68 , 69 , 70 ] amino acids;[ 71 , 72 , 73 ] or from easily available chiral diamines, i.e. trans ‐cyclohexane diamine.…”

Ammonium Salt‐Catalyzed Ring‐Opening of Aryl‐Aziridines with β‐Keto Esters

“…The reason why we opted for the N ‐tosyl protected 4a was because we previously (during the hydroxylation of 1 with oxaziridines 2 ) realized that sulfonamide groups provide a very good point of coordination for our bifunctional ammonium salts A . Besides our own catalysts A , (on which we put our main focus), we also compared the other classical and well‐established ammonium salt catalysts B , and C , and the recently reported bifunctional Cinchona alkaloid derivative D …”

Organocatalytic Dynamic Kinetic Resolution: An Update

“…In 2020, Papai, Takemoto and Tsukano developed novel chiral thiourea-derived quaternary ammonium salt 113 to promote asymmetric S N 2-type acetalization of enols 114 with racemic γ-chlorobutenolide 115. [34] The latter was submitted to fast racemization because of the presence of chloride anions, allowing DKR to occur (Scheme 24). Performed at 0 °C in a mixture of chlorobenzene and water as the solvent and in the presence of Cs 2 CO 3 as a base, the O-alkylation afforded a series of chiral acetals 116 with low to quantitative yields (30-> 99 %) and high enantioselectivities (80-90 % ee).…”