A short synthesis of (−)-dendrobine. Some observations on the nickel mediated radical cyclisation and on the Pauson–Khand reaction

The total synthesis of (−)-dendrobine was accomplished in 13 steps starting from (+)-verbenol. The key step is a radical cascade starting with a carbamyl radical generated by reaction of the N-benzoyloxy–carbamyl derivative of trans-verbenol with tributylstannane. This allows the one step establishment of three contiguous stereogenic centres, including the difficult cis-vicinal amino alcohol motif, and ultimately the control of the configuration of the remaining four asymmetric carbons. The synthesis also features the use of the Pauson–Khand reaction where an interesting solvent effect was observed. Thus, the use of a coordinating solvent such as acetonitrile was found necessary to suppress the formation of a ring-opened by-product resulting from scission of a CN bond. In an ancillary model study, we observed an unusual but interesting 1,4-hydrogen atom abstraction which, however, thwarted our initial synthetic plan.