Here's a minimal compilable sketch that successfully compiles for the QT Py RP2040 with the Adafruit_Si5351 on Wire1 on my setup. I fixed a trivial incompatibility the library had with the rp2040 core but it was nothing that would hold you up for more than a minute or two so I look forward to seeing what you've uncovered.
arduino-cli compile -b rp2040:rp2040:adafruit_qtpy --warnings all --output-dir /home/me/tmp --no-color (in directory: /home/me/Documents/sketchbook/RP2040_Zero/test)
Sketch uses 62048 bytes (0%) of program storage space. Maximum is 8384512 bytes.
Global variables use 10044 bytes (3%) of dynamic memory, leaving 252100 bytes for local variables. Maximum is 262144 bytes.
Compilation finished successfully.
I'm afraid I have no idea what "EatherKit si5351 example" is, nor the inclination to go looking for it. If you want free help, then don't put up obstacles.
You didn't provide that information until 14 posts into the thread. As mentioned, you're asking for free help. So do you understand how making it difficult for people to help you will discourage them from doing so?
If you look in the file "si5351.cpp", you'll see that the library is hard coded to use only the wire object. You'll need to modify the library to use it. Or, use a different one.
Both si5351.cpp and si5351.h need to be modified. Perhaps if you post your attempts, someone would help you.
If it were my project, I'd modify the init() function of accept a Reference to a TwoWire object as an optional third parameter. Then change all hard coded uses of the Wire object to use the supplied reference instead.