Vicinal Diols as Potentially Green H-Bond Donors: Application to an Accelerated MBH Protocol

Herein, the concept of biobased vicinal diols as alternative H-bond donors is presented. NMR study revealed superior electrophilic enhancement by ethylene glycol in comparison to other H-bond donors, duly supported by computational studies. As a case study, controlled experiments confirmed the better activation by 1,2-diols over mono-ols, diol regiomers, and other H-bond donors in the Morita-Baylis-Hillman (MBH) reaction. Reaction inhibition with lower conversion in the presence of an acid cocatalyst due to competing protonation of the H-bond acceptor was observed. As a practical application of this concept, a thorough investigation and optimization were carried out to mitigate the sluggishness of sp²-C electrophiles, particularly aliphatic aldehydes, in MBH reactions with various pronucleophiles. The sluggishness of the aliphatic aldehydes with respect to aromatic aldehydes has been assigned to competing amine-trapping zwitterions from side reactions with the electrophiles.