The collective total syntheses of (+/-)-hosieines A-C with a cage-like tetracyclic framework have been realized, which includes the first syntheses of hosieines B-C. The key strategy of the synthesis employs a one-pot domino reaction that involves Cu-catalyzed [3+2] cycloaddition, 1,6-enone formation, and 1,6-aza-Michael addition forming the 5/6/6-aza-tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4-aza-Michael addition reaction to afford the tetracyclic framework.The collective total syntheses of (+/-)-hosieines A-C featuring a cage-like tetracyclic framework have been realized. The key synthetic strategy features a one-pot domino reaction that forms two bonds and three consecutive stereocenters to construct the desired 5/6/6-aza tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4-aza-Michael addition reaction to afford the tetracyclic framework. image