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

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. Multitasking cat.: A multifunctional thiourea/ammonium salt catalyst has been developed that operates as a multiple hydrogen‐bond donor. By coordinating with both the nucleophile and the electrophile, this catalyst enables the synthesis of chiral acetals by dynamic kinetic resolution (DKR). This is the first example of an SN2‐type intermolecular asymmetric acetalization using an organocatalyst.