After departure, another pilot advised N8511Z that a cowl door was open. The pilot acknowledged, but continued the flight. During the VFR flight, witnesses heard a loud pop and observed the R22 helicopter break apart in flight. One witness observed a light airplane traveling in the opposite direction at the same time. The tail boom was the first piece of the helicopter found along the 584' long wreckage path. The main rotor separated from its drive shaft and there were multiple strikes to the tail boom. Metallurgical examination of the main rotor head components and examination of the engine revealed no evidence of malfunction or failure that could have contributed to the main rotor blade diverging and striking the tail boom, resulting in the in-flight separation of the tail boom. Examination of the right collective control tube revealed a fatigue fracture in the inboard wall of the tube where it is normally lightly loaded. The evidence did not support a conclusion that this was related to loss of main rotor control.