I'm looking to hear ideas to separate two similar compounds that differ only with one containing a single Cl and the other a single Br atom. Can they be separated?
Get into the lab, and try some stuff !!! I had to do similar many times when I was working.
Make up standard solutions of each individually, see if you can come up with ways to see a peak in each solution. Then mix portions of those two and see if there's separation.
If you don't get separation in a mix, vary one thing at a time. For example, was easy to program in a lower column temperature, and a higher column temperature, and see if the separation got better, worse, or stayed the same. That's the start of a mini Design of Experiments.
Do similar changing columns, mobile phase, trying a gradient, etc. When I had similar situation, I found that I could achieve separation by adding a few %THF to the mobile phase; another way that worked there was to use what was new then (intrinsically base-deactivated column) which actually reversed the order of elution and made quantitation much easier. Some column suppliers can supply technical help but they'd need to know the molecules, and won't happen fast; but they would love to have you keep buying their column regularly !
If you can, post names/structures of your two molecules.