Modular synthesis of bis-α-chiral amines using Ellman sulfinamide for consecutive <i>S</i>-to-<i>C</i> chirality induction/transfer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40184443.
- Also identified by DOI 10.1126/sciadv.adv2010 and PMC identifier 11970453.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Amines are ubiquitous components in pharmaceuticals. Increasing saturated substitutions (<i>sp<sup>3</sup></i>-hybridized carbon) at the amino center and the number of chiral centers can enrich the molecular diversity and chemical space, ultimately enhancing the success of drug development. However, the synthesis of such advanced amines is challenging due to a higher level of structural complexity and stereo-control. Here, we report a modular protocol for short de novo synthesis of bis-α-chiral amines. This protocol uses commercially available Ellman sulfinamide, <i>tert</i>-butanesulfinamide (<i><sup>t</sup></i>BS), as the exclusive chiral source to selectively produce all possible stereoisomers. Sequential formation of contiguous α-amino chiral carbons is achieved by chirality induction and transfer mechanisms that are both enabled by <i><sup>t</sup></i>BS, the stereoselective imine functionalization and alkyne-participated rearrangement reaction. The second step we developed is crucial for high diastereoselectivity, which is problematic in previous methods. The other coupling partners used in this protocol are abundant feedstocks, providing desirable chemical diversity in the products.