Citation:
Hu, M. ; Ding, H. ; Desnoo, W. ; Tantillo, D. J. ; Nairoukh, Z. . The Construction Of Highly Substituted Piperidines Via Dearomative Functionalization Reaction. Angew. Chem. Int. Ed. 2023, e202315108.
Abstract:
Nitrogen heterocycles play a vital role in pharmaceuticals and natural products, with the six-membered aromatic and aliphatic architectures being commonly used. While synthetic methods for aromatic N-heterocycles are well-established, the synthesis of their aliphatic functionalized analogues, particularly piperidine derivatives, poses a significant challenge. In that regard, we propose a stepwise dearomative functionalization reaction for the construction of highly decorated piperidine derivatives with diverse functional handles. We also discuss challenges related to site-selectivity, regio- and diastereoselectivity, and provide insights into the reaction mechanism through mechanistic studies and density functional theory computations.