When the whole ligand is selected as the alchemical region, the work values are too high (in fact, always significantly unfavorable, here), resulting in every move getting rejected. This is probably because the whole binding pocket undergoes changes when the ligand alchemically disappears (or appears) resulting in high work values. When we designate only the moving part of the ligand as the alchemical region, the work distribution gets shifted to lower values which results in reasonable move acceptance rates.