Synthetic Studies of Javaberine A Based on Intramolecular Hydroamination of Alkenes

A total synthesis of javaberine A was achieved through a lithium amide-mediated intramolecular hydroamination of an N-allyl aminoalkene. The desired hydroamination was accomplished using an excess of i-Pr NH with a substoichiometric amount of n-BuLi. Using an excess of both n-BuLi and i-Pr NH led to tandem cyclization, however, resulting in the construction of a tricyclic structure through the formation of one C-N and two C-C bonds in a single operation. Additionally, epimerization of the H8-H14 cis-benzyl tetrahydroisoquinoline to the trans isomer was achieved via β-elimination followed by intramolecular hydroamination.