Setting policy is Trump's job. Providing information to the President and then executing policy is Mattis' job. If Mattis can't do his job, then good decision for him to admit it and quit.
I personally suspect that Mattis got used to making decisions and pitched a fit when Trump went a different direction. I think it's past time we got out of Syria and let Russia pick up the ball and run with it for a while. We have friends in the region (Jordan), pseudo "allies" (Turkey) that have been playing us for fools, and we broke Iraq pretty badly so we ought to help them out a bit. But our policy of interfering in Syria to encourage regime change is an Obama/Hillary/Kerry disaster of an idea and it's time to quit that nonsense.