Synthesis of (-)-Dihydroraputindole D by Enantioselective Benzoylation of a 1,3-Diol Intermediate.

The enantioselective synthesis of (-)-dihydroraputindole D is reported. The key step is the desymmetrizing benzoylation of a prochiral 1,3-diol employing Trost's ProPhenol catalyst system, which has been applied for the first time to a cyclic molecule carrying geminal hydroxymethyl groups. The cyclopenta[f]indoline system was assembled by Au(I)-catalyzed cyclization of an alkynylated indoline precursor. (-)-Dihydroraputindole D was obtained in 17 steps and 8% overall yield starting from dihydroxyacetone. In combination with quantum chemical calculations of the ECD spectra, our synthesis allowed us to determine the absolute configuration (5S,7R) of the natural product (+)-raputindole D from the Rutaceous plant Raputia simulans.