Tapas R Pradhan, Abdikani Omar Farah, Kadiyala Sagar, Henry R Wise, Malempati Srimannarayana, Paul Ha-Yeon Cheong, Jin Kyoon Park
A key factor in the development of selective nucleophilic addition to allenamides is controlling the reactivity of electrophilic intermediates, which is generally achieved using an electrophilic activator via conjugated iminium intermediates. In this combined experimental and computational study, we show that a general and highly chemoselective hydroamination of allenamides can be accomplished using a combination of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and NaOAc. Experimental mechanistic studies revealed that HFIP mediates proton transfer to activate the allenamide, while the acetate additive significantly contributes to N-selective interception...
April 23, 2024: Journal of Organic Chemistry