Recent Advances in the Organocatalytic Enantioselective Synthesis of Functionalized β‐Lactones

Abstract

This Focus Review highlights recent developments in the organocatalytic enantioselective synthesis of β-lactone derivatives. Owing to the importance of β-lactones as a heterocyclic motif that is present in a variety of natural products and biologically active molecules, several catalytic methods have been developed for the synthesis of these compounds in their enantiomerically pure form. Organocatalytic methods that employ N-heterocyclic carbenes (NHCs), cinchona alkaloids, isothioureas, 4-dimethylaminopyridine (DMAP) derivatives, and phosphines have allowed the highly enantioselective synthesis of β-lactones from cheap and readily available starting materials. Moreover, the inherent strain in the four-membered ring of β-lactones has also been utilized in further synthetic transformations, thus making β-lactones a versatile intermediate in organic synthesis.

Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins

“…In situ ring opening with an amine nucleophile generates isolable highly enantioenriched products in up to 92:8 dr and in >99:1 er.β-Lactones are versatile synthetic building blocks and significant components of many bioactive natural products. 1,2 As a consequence, a range of enantioselective synthetic methods for their preparation has been developed, with both Lewis acid and Lewis base catalyzed approaches common. 3 In terms of Lewis base catalysis using tertiary amines, the use of cinchona alkaloids and chiral DMAP derivatives has been extensively used to promote β-lactone formation through the generation of an intermediate C(1)-ammonium enolate.…”

Bifunctional N-Heterocyclic Carbenes Derived from l-Pyroglutamic Acid and Their Applications in Enantioselective Organocatalysis

“…An interesting bridged preNHC derived from camphor was reported by You et al for the intramolecular crossed aldehyde-ketone benzoin reaction . NHC-catalyzed reactions have been intensively reviewed by several research groups . However, all focus on normal NHCs without additional functional groups.…”

Intramolecular α-Oxygenation of Amines via N -Heterocyclic Carbene-Catalyzed Domino Reaction of Aryl Aldehyde: Experiment and DFT Calculation

“…In the last few decades, dramatic progress in N-heterocyclic carbene (NHC) catalysis has enabled the development of various synthetically important reactions, [1][2][3][4][5][6][7][8][9][10][11][12][13] including oxidative reactions involving either simple or α,β-unsaturated acyl azolium intermediates (Scheme 1, reactions a and b). [14][15][16] Generally, the NHC-catalyzed generation of acyl azolium intermediates and acylation reactions through such intermediates has been well established (Scheme 1, reaction a).…”