One, and a critically massive problem with this concept is who would Isabella marry in lieu of Ferdinand? There are historically strong and compelling reasons as to why they got married. And, the timing is very bad for any plausible alternatives which leads to the implausible such as something as dramatic as one of the principals dying before marriage, or a Castillian change in attitude in regards to France, etc. You would be better off constructing an alternative history where Isabella was born with a Y chromosome and take it from there.
Oh, and in any scenario that has this kind of seismic shift in Western European history - Napoleon, along with a vast multitude of other significant personae over the next 5 hundred years, doesn't exist.