J Am Chem Soc. 2022 Nov 1. doi: 10.1021/jacs.2c07918. Online ahead of print.
ABSTRACT
Amidines are a ubiquitous class of bioactive compounds found in a wide variety of natural products; thus, efficient strategies for their preparation are in great demand. Specifically, their common structural core decorated with three substituents sets amidines as perfect candidates for multicomponent synthesis. Herein, we present a highly modular metal-free multicomponent strategy for the synthesis of sulfonyl amidines. This work was focused on selecting readily accessible reagents to facilitate the in situ formation of enamines by the addition of amines to ketones. These components were coupled with azides to provide a broad reaction scope with respect to all three coupling partners. Aromatic and aliphatic amines and ketones were tolerated under our reaction conditions. Likewise, the presence of a methyl group on the ketone was critical to reactivity, which was leveraged for the design of a highly regioselective reaction with aliphatic ketones. A biologically active compound was successfully synthesized in one step, demonstrating the practical utility of our methodology. Finally, the postulated mechanism was investigated and supported both experimentally and by means of a multivariate statistical model.
PMID:36318611 | DOI:10.1021/jacs.2c07918
