Tandem Double-Intramolecular [4+2]/[3+2] Cycloadditions of Nitroalkenes. Studies toward a Total Synthesis of Daphnilactone B: Piperidine Ring Construction

Two model studies in support of a total synthesis of the complex polycyclic alkaloid daphnilactone B
have been completed. The objectives of the models studies were to demonstrate the use of a tandem
double-intramolecular [4+2]/[3+2] nitroalkene cycloaddition for the stereocontrolled construction of four
of the rings in the core of the natural product. The first model study established the ability to create a
pyrrolidine ring corresponding to ring A of daphnilactone B through a modification of the dipolarophile
and subsequent functional group manipulations. The second model study required the modification of
the dienophile in the [4+2] cycloaddition to accommodate the formation of a piperidine ring (ring B of
daphnilactone B). Nitroalkene 26 containing a diene as the dienophile served well in the tandem
cycloaddition to afford the nitroso acetal 38a in 77% yield. Subsequent functional group manipulations
allowed for the high-yielding conversion to the core of daphnilactone B.