Di2 parts can be connected together in any physical layout you like including using inline junction boxes to connect cables together end-to-end, so no problem coping with unusual frames.
Shimano do make one triple Di2 front mech but it's an MTB one. One odd quirk of the Di2 system is you can't mix road and MTB mechs on the same system, so you'd need to use it with an MTB rear mech.
No such limitation applies to shifters, so you can still use road shifters, or even have multiple sets of shifters of different types (up to 6 IIRC) on the same bike, and you can program what each button does separately.