Sustainable Crafting of Biomass-Derived Vicinal Diols as H-Bond Donors in Promoting Morita-Baylis-Hillman Reaction

This work presents an integrated strategy to mitigate the sluggishness of sp2-C electrophiles, particularly aliphatic aldehydes, in Morita-Baylis-Hillman (MBH) reactions with various pro-nucleophiles. The approach encompasses the usage of biomass (lignocellulose) derived 1,2-diols as promising H-bond donors activating the MBH precursors, and stabilizing the zwitterionic intermediates and transition states, enabling faster escalated yields affording an efficient, sustainable approach with a broad array of substrates. Controlled experiments confirmed the superior activation by 1,2-diols over mono alcohols and other diol regiomers, duly supported by spectroscopic and computational studies. Acid co-catalysts, functioning as competing promoters, significantly modulates the H-bonding capacity of the diol promoter through the protonation of electrophilic precursors, thereby effectively diminishing the intricate H-bond interactions involved in the catalytic process. Additionally, the protocol ensues a direct access via in situ trans-esterification to potent bioactive moieties against P. Falciparum and Leishmaniasis.