Is something like this possible?
No. All you can do is detect the mouse going into the iframe, and potentially (though not reliably) when it comes back out (ie. trying to work out the difference between the pointer passing over the ad on its way somewhere else versus lingering on the ad).
I imagine a scenario where there is an invisible div on top of the iframe and the the div will just then pass the click event to the iframe.
Nope, there is no way to fake a click event.
By catching the mousedown you'd prevent the original click from getting to the iframe. If you could determine when the mouse button was about to be pressed you could try to get the invisible div out of the way so that the click would go through... but there is also no event that fires just before a mousedown.
You could try to guess, for example by looking to see if the pointer has come to rest, guessing a click might be about to come. But it's totally unreliable, and if you fail you've just lost yourself a click-through.