American Chemical Society
jo3c02168_si_001.pdf (2.64 MB)

Chemoselective Intramolecular Morita–Baylis–Hillman Reaction; Acrylamide and Ketone as Sluggish Reacting Partners on a Labile Framework

Download (2.64 MB)
journal contribution
posted on 2024-01-02, 09:46 authored by Kishor Chandra Bharadwaj
Chemoselectivity is an important issue frequently encountered while working over labile precursors. Carbonyl compounds with a heteroatom at the β carbon are sensitive precursors because they are prone to elimination under different conditions. Morita–Baylis–Hillman (MBH) reaction, although a widespread method for C–C bond formation, has its own limitations. Acrylamide and ketone are such limitations of the MBH reaction. Using them together for an intramolecular MBH (IMBH) reaction on a labile framework prone to elimination is a significant 2-fold synthetic challenge. A highly chemoselective IMBH reaction on such precursors has been established using 1,4-diazabicyclo[2.2.2]­octane (DABCO) as a promoter. The protocol leads to quick access to a diversely substituted and functionalized piperidone framework in high yields. Various substitution patterns in the form of 34 successful examples have been studied. A diastereoselective version and tolerance to various functional and protecting groups are the added advantages of the developed methodology. A tertiary carbon at the β position of ketone, however, led to complete reversal of selectivity and gave only the elimination product. Control experiments toward a better understanding of the substitution pattern, role of catalyst, and mechanistic study have been carried out. As an application of the IMBH adduct, a one-step allylic rearrangement for the dihydropyridone framework has also been demonstrated.