Look at the manual of the Focusrite. From what I can see it has multiple analogue outputs, so you should be able to connect both main speakers and subwoofer to the Focusrite. From what I can see the Focusrite has balanced analogue outputs with TRS Plugs. The Yamaha has both Neutrik and TRS inputs, so you should be fine with a TRS to TRS cable to connect Focusrite to Yamaha. This way you can use the high pass filter on the Yamaha to relieve the main speakers from the very lowest frequencies (the sub will deal with those). Set it at something like 40 Hz, or maybe a bit higher.
Consult Focusrite about how to connect the sub to the Focusrite. At the very least this needs a TRS to rca cable.
You may consider a DSpeaker Antimode 8033 room eq unit to equalize the subwoofer and tame room modes. See here: http://www.theabsolutesound.com/articles/dspeaker-anti-mode-8033-dsp-subwoofer-equalizer-tas-204/ I have been very pleased with mine. In your case the stereo model may be convenient because it takes L and R inputs and has mono outputs (ask the DSpeaker importer for which types of cables you need).
If the Focusrite somehow cannot output signals to both the power amp and the sub, you will have to connect at speaker level, using an attenuation cable from the power amp’s outputs to the sub. But it had better be able to handle the Yamaha’s big power.
Since the Focusrite does not have tone controls (unless hidden somewhere) and for as long as you are only using a computer as your source, install the free Equalizer Apo (plus Peace interface) software on your computer. This is an advanced software equalizer that you can use for basic tone control, but also for more detailed parametric equalization. In fact, if you use the REW software and a UMIK-1 calibrated microphone you can do subwoofer equalization with this as well. But REW is hard work. So to keep it simple, use the Antimode for sub eq and the Equalizer Apo (without REW) as basic tone control. Use the high pass filter on the Antimode to relieve the sub from havng to reproduce the very lowest frequencies (say, below 15 Hz). This is a large room for a modest sub, and lowest frequencies are the hardest work (they need much more energy).
Consult Focusrite about how to connect the sub to the Focusrite. At the very least this needs a TRS to rca cable.
You may consider a DSpeaker Antimode 8033 room eq unit to equalize the subwoofer and tame room modes. See here: http://www.theabsolutesound.com/articles/dspeaker-anti-mode-8033-dsp-subwoofer-equalizer-tas-204/ I have been very pleased with mine. In your case the stereo model may be convenient because it takes L and R inputs and has mono outputs (ask the DSpeaker importer for which types of cables you need).
If the Focusrite somehow cannot output signals to both the power amp and the sub, you will have to connect at speaker level, using an attenuation cable from the power amp’s outputs to the sub. But it had better be able to handle the Yamaha’s big power.
Since the Focusrite does not have tone controls (unless hidden somewhere) and for as long as you are only using a computer as your source, install the free Equalizer Apo (plus Peace interface) software on your computer. This is an advanced software equalizer that you can use for basic tone control, but also for more detailed parametric equalization. In fact, if you use the REW software and a UMIK-1 calibrated microphone you can do subwoofer equalization with this as well. But REW is hard work. So to keep it simple, use the Antimode for sub eq and the Equalizer Apo (without REW) as basic tone control. Use the high pass filter on the Antimode to relieve the sub from havng to reproduce the very lowest frequencies (say, below 15 Hz). This is a large room for a modest sub, and lowest frequencies are the hardest work (they need much more energy).