Protecting Groups as Dispersive Directing Groups: Toward the Asymmetric Synthesis of Altemicidin

We report progress toward the asymmetric total synthesis of altemicidin, a monoterpene alkaloid featuring a 6-azatetrahydroindane core. A diastereoselective 1,3-dipolar cycloaddition with TMS-diazomethane enabled the construction of a key pyrazoline intermediate. Computational analysis (EDA/NCI) revealed attractive London dispersion forces as the origin of the unexpected stereoselectivity. An effective method to convert the initial silylated 1-pyrazoline into a stable 2-pyrazoline was developed. Selective reductive trifluoroacetylation and SmI 2 -mediated N–N bond cleavage afforded a 1,3-diamine suitable for further functionalization.