If you’re on Windows, and you’re seeing this error saying The connection to Microsoft Exchange is unavailable when you start Outlook with a profile for an Exchange mailbox, you’re not alone. Many Outlook users are reporting it. But the good news is you can fix it easily by yourself.
How do I fix it?
This problem is most probably due to the User Shell Folders registry key. If this registry key doesn’t contain all of the required data, the problem would occur.
So you can fix this error through importing the User Shell Folders registry key from a working Windows User Profile.
See how:
On a working Windows computer, do these:
1) On your computer, press the Windows logo key 
and R at the same time to invoke the Run box.
2) Type regedit and press Enter to open the Registry Editor window:
Click Yes when prompted by the User Account Control.
3) Go to HKEY_CURRENT_USER\Software\Microsoft\Windows\CurrentVersion\Explorer\User Shell Folders.
4) Click User Shell Folders, then File > Export…
5) Select a place to save the export file. Then type a name to it, like export, and click Save.
6) Copy the saved .reg file to the computer showing the error.
On the computer showing the error, do these:
IMPORTANT: Serious problems could happen if your modify the registry incorrectly. So please back up the registry before you modify it.
7) On your keyboard, press the Windows logo key and R at the same time to invoke the Run box.
8) Type regedit and press Enter to open the Services window:
Click Yes when prompted by the User Account Control.
9) Click File > Import…
10) Click the .reg file pasted before, then Open. Or just double-click the .reg file.
11) Close the registry window.
12) Start your Outlook to check to see if it works.
How to back up the registry on your computer:
1) On your computer, press the Windows logo key and R at the same time to invoke the Run box.
2) Type regedit and press Enter to open the Services window:
Click Yes when prompted by the User Account Control.
3) Go to HKEY_CURRENT_USER\Software\Microsoft\Windows\CurrentVersion\Explorer\User Shell Folders.
4) Click User Shell Folders, then File > Export…
5) Select a place to save the export file. Then type a name to it, like export, and click Save.