< speculation >
Probably because the wing can't really handle that. The 345/346 wing is heavily modified compared to the 332/333/342/343 wing. My guess it requires the outboard engines in place to mitigate wing bending moment. Making it a twin would either require wing reinforcement (the 332/333 wing is already reinforced compared to the 342/343 wing for this exact reason) or moving the engines outboard. Moving the engines outboard would have required pretty much a new wing so that was out.
Furthermore, for the mission (very long haul), it is by no means a given that fuel consumption for a "335/336" would be less than for the 345/346. As I understand it, on long routes the 340 is more efficient than the equivalent 330. This is all before engine maintenance costs of course.
< /speculation >
"There are no stupid questions, but there are a lot of inquisitive idiots." - John Ringo