Multigram Synthesis of Heterabicyclo[n.1.0]alkan-1-yl Trifluoroborates

An approach to the synthesis of oxa- and azabicyclo[n.1.0]alkan-1-yl trifluoroborates on a multigram scale was developed. Two synthetic strategies were evaluated: the first based on the lithiation-borylation of the corresponding 2-bromoallyl derivatives, and the other relying on regioselective hydroboration of the appropriate hetera-substituted enynes. The second method appeared to be more efficient in terms of scalability and substrate scope. Further steps included ring closing-metathesis, mild palladium-catalyzed cyclopropanation with diazomethane, and reaction with KHF(2)and furnished the title compounds in up to 50 g scale in a single run (10-41 % overall yield, 4-5 steps).