When you are medium, have a reach weapon, and are adjacent to a large creature, are you allowed to make an attack on the parts of the creature that are further away?
Strict RAW would say no:
Reach: You use a reach weapon to strike opponents 10 feet away, but you can't use it against an adjacent foe. (source; emphasis mine)
Since the large creature is adjacent, a reach weapon can't be used against it.