Pharmaceuticals, molecular catalysts, and secondary metabolites often contain
nitrogen. The problems faced synthesizing compounds which contain nitrogen was
because of the Lewis base reactivity of nitrogen lone pairs, and the acidic protons of
some nitrogenous functional groups. We developed two methods for the synthesis of
nitrogeous compounds. Additionally, we successfully constructed the
heterotetracyclic core of himgaline.
The aminal radicals were generated by reduction of the corresponding amidine or
amidinium ion. The intermediate radicals participate in C−C bond- forming reactions
to produce fully substituted aminal stereocenters. No toxic additives or reagents are
The regioselectivity and diastereoselectivity was investigated in pyridinium oxide
cycloadditions using complex substrates. The reaction is reversible under the reaction
conditions. High levels of diastereoselectivity and regioselectivty are observed, which
can be attributed to minimization of syn-pentane interactions in the products.
The stereo- and region-selective intramoleculer pyridinium oxide cycloaddition
successfully forms two bonds and builds four stereocenters in a single step. These key
cycloaddition reactions are particularly suitable to the challenge of preparing multiple
rings with control of stereochemistry. It has been shown that the new methodology
replacing acid-base strategy would enhance the efficiency of alkaloid synthesis.