For the past 5+ years, simple alkenyl alcohol substates have been on our wish list of “ideal” substrates for directed three-component alkene difunctionalization. However, extensive efforts within our lab and by others have proven that these starting materials are especially challenging due to a number of competitive side reactions that can arise (cyclization, alcohol oxidation, alkylmetal chain-walking, etc.). In an exciting study appearing online today in J. Am. Chem. Soc., Taeho and Nana together with Bristol Myers Squibb collaborators Peter, Klement, and Hao, have demonstrated a creative approach to integrate alkenyl alcohols into three-component carboamination that hinges on judicious tuning of the leaving group on the nitrogen electrophile. By carefully modulating the LUMO energy of this reaction partner, high pathway selectivity for the desired three-component coupling can be achieved across a broad array of substrates. Congrats to the team on this awesome advance!
For a link to the published manuscript in J. Am. Chem. Soc., click here: https://pubs.acs.org/doi/10.1021/jacs.1c07112.
As a reminder, a pre-print of this paper was published back in March: https://chemrxiv.org/engage/chemrxiv/article-details/60c7562e567dfebe64ec63f7