Description
Due to a problem in the Quartus® II software, the Nios® II/e including both classic and Gen2 doesn't boot when the Nios II and boot memory are in different clock domains and the Handshake type is chosen as clock crossing adapter in Qsys interconnect.
Resolution
To work around this problem, put Nios II and boot memory in the same clock domain, use the FIFO adapter instead of the Handshake one, or use Nios II/f instead of Nios II/e.
This problem is scheduled to be fixed in a future release of the Quartus II software.