The peephole optimiser already makes optimisations like that in a couple of places (e.g. set -> frozenset):

>>> def f(x):
...    if x in {1, 2}: pass
...
>>> f.__code__.co_consts
(None, 1, 2, frozenset({1, 2}))

It's name lookup semantics that are the real minefield. It's one of the reasons PyPy's JIT can be so much more effective than a static optimiser - because it's monitoring real execution and inserting the appropriate guards it's not relying on invalid assumptions about name bindings.