Derivatisation of chiral adducts from reactions of N-Acyl-1,3-oxazolidine-2-thiones with Propargylic Acetals

Abstract

The construction of enantioselective carbon-carbon (C-C) bonds is a fundamental challenge in organic synthesis, especially in the pharmaceutical industry, where the precise control of stereoisomerism can significantly influence the efficacy and safety of drugs. In the past, enantioselectivity in C-C bond formation was achieved using chiral auxiliaries. Our group developed several methodologies involving such auxiliaries, and while they provided excellent stereochemical control, they were proved inefficient due to the need for stoichiometric amounts of them. The drive for more efficient synthetic methods, along with the rise of asymmetrical synthesis, led to the development of catalytic systems, which can achieve stereocontrol without the drawbacks associated with chiral auxiliaries. Influenced by Evans, chiral nickel (II) complexes were used, as they facilitate direct reactions that form new C-C bonds enantioselectively, while reducing the waste generated, thus aligning with the principle of atom efficiency. As mentioned before, chiral nickel (II) complexes were employed along with N-acyl-1,3-thiazinane-2-thiones. Initially, these methods focused on creating single stereocentres, but more recent efforts have expanded these methodologies to simultaneously create two stereocentres via aldol reactions. In recent years, our focus has been on the use of propargylic acetals as electrophiles to increase the scope of the process, initially centered on aromatic acetals. Adding unsaturated chains enables a wide array of useful compounds, as alkanes and alkenes by reduction reactions, carbonyl groups through hydration reactions, or cycles via Pauson-Khand cyclisations. The development of these methodologies underscores the ongoing innovation in enantioselective synthesis, driven by the need for more efficient, sustainable, and versatile approaches to constructing complex, chiral molecules.