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Smoke detectors are required in the return side by the IMC 606.2.1. I'm not sure, but I think NFPA 90 has some requirements for detectors as well.

I wouldn't worry about the negative pressure too much (it's a good thing in a bathroom). Most bathroom doors utilize a closer, and the resistance from the closer should provide enough force to counter act the pressure. The easiest way to overcome this would be to swing the door out if possible.

Just finished a project like this. We had to cool a restroom area in a large unconditioned warehouse. We went with something similar to your second option above. We used a mini-split to condition the space. We put the bathroom exhaust on a delayed timer to allow the fan to run after the bathroom...

It may be a flexible connection (DS045 in section 4.5 of SMACNA CAD standard)