Henry-Nef reaction: A practical and versatile chiral pool route to 2-substituted pyrrolidine and piperidine alkaloids

Article abstract of DOI:10.1016/j.tet.2013.05.055

The paper describes the synergistic protocol developed by combinatorial Henry and Nef reaction for the synthesis of 2-substituted pyrrolidine and piperidine alkaloids containing 1,3-aminoketone and 1,3-amino alcohol units. The utility of the protocol is demonstrated by asymmetric synthesis of 12 natural products of which asymmetric synthesis of (-)-N-methylpelletierine is presented for the first time. The one-carbon homologation described also provides an alternate route for the synthesis of key intermediates homoprolinol and homopipecolinol used as synthetic precursors for several alkaloids and construction of β-amino acids from α-amino acids.