The simple answer to this is that I-Pac should allow you to utilize alt+F4, my understanding is that most people don't use ctrl, alt and shift keys as much as possible so that there are no conflicts with the OS but with iPac you can as stated on the website
Shift functions. Holding "Start1" and pressing other buttons sends a
range of codes for MAME functions such as "escape", "Coin 1", "tab",
"enter". This means no extra buttons are needed on the cabinet. In
programmable mode any input can be the shift key and all keys can be
programmed with a shifted code.
What this implies is that you can assign an alternate key function so that you won't get a conflict unless you are holding start1 - this way you could program in that (Start1+"otherkey") = alt+F4 without the problem of conflict.
I really hope this helps - I haven't built one myself but i have been part of building one with my friends and i believe this is how we managed it as we ran into the same issue.
Might take some playing with and depending on the emulator you might be able to change the key config with that. or get some macro software that says when esc is pressed procede with alt-f4