Nimbostratus
CirrusHave you deployed this using the iApp? Do have the _sys iRule assigned to the virtual server? I just tested my setup and autodiscover worked just fine(setup my account on iOS device using autodiscover) on 12.1 - so I am fairly certain something is amiss in your setup.
NimbostratusI don't think it's the Autodiscover piece that's failing (per say)....I'm having the same issue and have a case open right now.
Full Disclosure: We have a complex setup (APM front end w/o365 STS and Exchange Client Access iApp that forwards traffic (Exchange related) to another LTM with the Exchange Client Access iApp configured), so the problem may be something else - but this rings a bell to me...
It's looking more like after the redirect that happens, O365 is trying to reauthenticate with the STS and either: 1) O365 gets a response it does not like or 2) the APM resets the connection. Were doing packet captures, log traces, etc. to try and narrow it down further...
What we're finding is Autodiscover works fine for internal (on prem) mailboxes. But when O365 comes back to our STS to authenticate for a migrated mailbox (after a 302 redirect which does in fact succeed), the POST from O365 during the Autodiscover process contains authentication headers but the APM is resetting the connection for some reason.