In a battle of taijutsu..
Tsunade has the raw power to kill practically anyone in one hit. But from what we have seen in the manga and anime. She is on the slow side, and alot of the times, her attacks dont connect. Primary example. VS part 1 base Kabuto, BEFORE the blood spilling, she couldnt even touch the guy. Eventually she was finally able to, but it took her a while. Which was evident because they were both breathing pretty hard at that point. Part 1 base Kabuto with a soldier Pill was giving her problems..
Now imagine her trying to fight someone like Madara, who has far more experience on the battle field in the frontlines, who is much faster than her, and also is a master of the sharingan.
Every punch she throws at him, he can easily predict it. If a sasuke could predict 1tail Naruto's movements (who is faster than tsunade) than Madara can predict her no problemo. She throws a punch, with her speed, Madara would easily see it coming, and counter it, prolly break her arm.