I understand the point about cumulative losses in the turbine/ compressor etc. It is true though that a super charger ahs a 0% effecient turbine in that it doesn't have one. And yeah I agree there's no point to series turbocharging unless you're shooting for 45-60psi boost. I still think it would be a cool project if anyone was brave enough to try it. 60psi boost would make one mean machine! Be verging on a turbo compound engine like was used in aviation and locamotion before gas turbines were enabled through better materials.
By breaking blocks do you mean the bore, block its self shearing it in torsion or something else? I'm interested to know more about the mechanical limits. I would think that lowering compression ratio would lower the peak pressure in the cylinder but this equally increases exhaust temperature so perhaps the exhaust valve will melt unless there's water injection (shown to reduce peak and exhaust temperatures).
The thing that gives me an idea it might work in a 4cyl is that the crank and everything else has to be strong enough for peak pressure and peak inertial forces (I think the inertial forces are generally larger once the revs get up) and that the power strokes don't really overlap. Maybe this is a project that needs to be done to find out?
I'd gladly donate some time and labour to it. Or maybe I'm crazy, fun thinking about it in any case.