For a number of security related considerations, “ClickOnce” requires that the main entry point assembly (the .exe file) be compiled with the 2.0 version of the .NET Framework. Other assemblies in the application can still be compiled with previous versions of the .NET Framework.

If you need to overcome this restriction (say you want to deploy an existing application for which you do not have the source), you can create a V2.0 .exe that does nothing except launch the exe of the application. However, this will require that your application have a high degree of trust.