Nonracemic Frontalin via Copper- and Palladium-Based Skeletal Construction and the Asymmetric Dihydroxylation

Article abstract of DOI:10.1021/jo00048a014

The new higher order organocuprate, Li2Cu(CN)(C(OMe):CH2)2, prepared through a Sn -> Li -> Cu transmetalation sequence, was found to efficiently couple with allyl bromide producing 2-methoxy-1,4-pentadiene (3) which is efficiently converted to the ketal 4.Hydroboration of 4 with 9-BBN-H and the selective oxidation of this adduct with trimethylamine N-oxide (TMANO) produces 9-oxa-10-borabicyclo<3.3.2>decane 5, which undergoes Pd-catalyzed cross coupling with 2-bromopropene producing 6, thereby accomplishing the construction of the frontalin carbon skeleton in 63 percent overall yield from allyl bromide.The Os-based dihydroxylation of 6 followed by ketalization either produces the racemic pheromone ((+/-)-1) or, with the Sharpless catalytic asymmetric dihydroxylation (dihydroquinine ligand) procedure, results in the selective formation of the S enantiomer in 35 percent ee.The de determined from the 13C NMR spectra of the diastereomeric Mosher's monoesters (9) was found to provide useful corroborative information on the optical purity of the intermediate 1,2-diols 7.