Creating U-235 takes a lot of work by almost all chemical/physical methods.

https://www.osti.gov/opennet/manhattan-project-history/Event...

Of course, once you can bootstrap a nuclear reactor, things get a lot easier because now you have Plutonium. Of course, Plutonium is rather toxic and working it metallurgically is problematic.

Edit: Plutonium also seems to require an implosion device. Implosion engineering is quite hard.