A vanadyl ion bound to a cucurbituril (CB) host was reported to oxidize pentane to 2-pentanol in the presence of an oxidizer. DFT calculations suggest that the catalyst selectively reacts with stronger C-H bonds in pentane over weaker C-H bonds in cyclohexane due to size exclusion by the CB host. The active catalyst is an unprecedented vanadium superoxo species bound to the host, and the selectivity toward secondary over the primary C-H bond is the result of a higher degree of charge transfer from the secondary compared to the primary position.