I've seen many variations of this issue and it always boils down to security. On the latest builds, any flavor of 2.1.42, I find that I have to log on as administrator, install as administrator, run as administrator and even then, I hope for the best.
Often several uninstall-reinstall cycles before we can sync properly. Often times, I move forward to the latest build from the support site, then roll back to the latest release from the portal for the client web and then find all is well.
The last puzzle piece remaining for me as of today is that we often see the automatic sync fail. When I click the Sync button, the sync happens, the tables.xml file is updated properly, the checksums are updated etc. When I leave it to do so on its own, it will not sync.
Is there a registry key or folder or file that needs to have the security set to allow the software access? Either by Trusted Installer or some other manner? Administrator just doesn't seem to be enough in very secure environments