120016-39-9Relevant academic research and scientific papers
Aza-cope rearrangement-Mannich cyclizations for the formation of complex tricyclic amines: Stereocontrolled total synthesis of (±)-gelsemine
Earley, William G.,Jacobsen, Jon E.,Madin, Andrew,Meier, G. Patrick,O'Donnell, Christopher J.,Oh, Taeboem,Old, David W.,Overman, Larry E.,Sharp, Matthew J.
, p. 18046 - 18053 (2005)
A detailed examination of the use of aza-Cope rearrangement-Mannich cyclization sequences for assembling the azatricyclo[4.4.0.02,8] decane core of gelsemine is described. Iminium ions and N-acyloxyiminium ions derived from endo-oriented 1-methoxy- or 1-hydroxybicyclo[2.2.2]oct-5-enylamines do not undergo the first step of this sequence, cationic aza-Cope rearrangement, to form cis-hydroisoquinolinium ions. However, the analogous base-promoted oxy-aza-Cope rearrangement does take place to form cis-hydroisoquinolones containing functionality that allows iminium ions or N-acyloxyiminium ions to be generated regioselectively in a subsequent step. Mannich cyclization of cis-hydroisoquinolones prepared in this way efficiently assembles the azatricyclo[4.4.0.02,8]decane unit of gelsemine. Using a sequential base-promoted oxy-aza-Cope rearrangement/Mannich cyclization sequence, gram quantities of azatricyclo[4.4.0.02,8]decanone 18, a central intermediate in our total of (±)-gelsemine, were prepared from 3-methylanisole in 12 steps and 16% overall yield.
