I run this setup with the left hand buttons for downshifts and the right hand buttons for upshifts. The Di2 shift buttons are tiny so this actually works better than the original setup, where it was very hard to hit the correct button. The new shifters are meant to be better.
I run R785 shifters and XTR Di2 mech. Went with XTR as it has the clutch, couldn’t face bangbangbangbang down every trail. 40t Rotor ring with 11-32 cassette. Never had the chain come off (and that’s with some fairly adventurous off-reading) and the gearing is fine round the Surrey Hills. Did Dirty Reiver on it last year too, no problems. It’s a brilliant setup.
One snag is that with a smaller cassette I needed to file down the mech mount bracket a bit as otherwise the B tension was too strong and the top jockey wheel sat too far from the cassette. It would be fine with an MTB cassette though.
You can’t mix road front mechs and mtb rear mechs though, so if you decide you want a front mech you’ll have to change the rear mech too.