> Is it possible to upgrade a two–data center Cassandra 4 deployment to 
> Cassandra 5.0 without downtime, using a node-by-node rolling upgrade approach?

Yes, this scenario is supported and, if done correctly, should not result in 
any downtime. Just be aware that topology changes are not possible while 
running mixed versions, so you probably want to plan to complete the update 
procedure in a reasonably short amount of time.
>
> Out of curiosity, I tried adding a second data center running Cassandra 5.0 
> to a test cluster based on version 4. When starting the Cassandra 5 nodes, 
> they fail to synchronize their schema versions.

Adding new nodes (both in an existing or a new data center) is a topology 
change, which is not possible with mixed versions. Either upgrade your existing 
DC(s) to C* 5 first and then add the new DC or add the new DC using the version 
of C* 4 that you are also using on the existing nodes.

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