First off, Good Luck
Word to the WISE, replacing oxygen sensors on the 2013 - W221 will bring factory showroom performance back to the car you didn't realize was missing and it is quite amazing. However, the upstream sensor on drivers side as shown above cannot be changed easily; the other 3 are not so bad but are achievable with patients and the right tools. You can see the upstream driver side oxygen sensor under the hood very well, you just can't reach it by hand. Its also pointing towards the heat shield above it which means you'll have a hard time getting a socket on it. To do so, you'll need to cut the wire off at top of it even when using an oxygen sensor socket that's fully open down one side. The electrical connector is also between the engine and the firewall just below the heater control valve which means you cannot get your hands on it to unplug it.
To do this job I'd recommend either putting the car in the air and lower the exhaust in which case you would easily be able to change all 4 of them, or you have a kid that can help you because very small hands and a small arm are necessary for the driver side upstream oxygen sensor. I learned a lesson on this 1 hard to reach sensor, the factory obviously put it in a place inaccessible to an adult hand and arm. A kid however can reach it from below if you have one, if not, you may want to consider renting a neighbors kid who wants to learn something about working on cars. Who knows, maybe you'll inspire a future Mercedes technician.
To unplug the upstream driver side sensor, I found a pair of 15 inch vice grips at Harbor Freight. I used these to grab one side of the plug and clamping on it from under the hood from above, while using a very long flathead screw driver to disengage the clip then using a pair of 15 inch long needle nose pliers to unplug the other side (long vice grips would have been a better choice). Would have been better to get two pairs of the long vice grips instead of needle nose pliers, so keep that in mind. Then I almost couldn't plug the new one back in from below due to reach, in which case a small arm and hand will come in handy. You'll need to leave the vice grip clamped on the receiving plug to leverage pushing the sensor plug back into it by hand because you'll be using only fingers. But before plugging it in you'll need to put the new sensor back in the pipe. To do this, I dangled it from above while using fingers from below to slowly screw it in, a kid would be best for screwing it in from below and someone up top the twist the wire as its turning. If I ever do them again myself, the exhaust must come down. If I don't have access to a lift, then I would recruit a kid to help or else take the car to the dealer. I'm convinced the dealer tech lowers the exhaust to do this.
I tried all kind of tools for this job but found or would have found the ones below to help best:
15 inch vice grips - get 2 pair
22 MM stubby open end wrench
22 MM open end crows foot wrench
22 MM oxygen sensor sockets - one should be deep well fully opened down the side for upstream driver side sensor
3/8 Ratchet and a couple size extensions
3/8 Ratchet universal joint
Gorilla tape to hold socket and universal joint to extension
15 inch wire cutters would have been nice to cut the wire at top of sensor before attempting to remove it, so socket slides right on it.
15 inch needle nose pliers
Hammer to tap wrench when trying to loosen old sensors
Very long flathead screwdriver
All 4 of my sensors were fairly easy to loosen, so they were not stuck like many people experience, only they are in very awkward positions to reach. Dropping exhaust would be way easier for changing the oxygen sensors on this car if you can get the car raised high enough but you would need a power or air ratchet to remove hard to reach exhaust bolts.
If you have the money, I'd pay the dealer to do this but first make some unique marks on your 4 sensors so you can check to see if they really changed them all. You'll find them before (upstream) of the CAT and one after (downstream) of the CAT on both sides. As much work as this is, do your self a favor and buy OEM as you'll not want to do it over.