scan large then compress can result in less distortion.
assuming same source.
1. scan at 8 bit per pixel, then copmressed using lossy JPEG at 6 bpp. this is the best result you can get.
2. scan at 5bpp, then compress using lossless TIFF, you can only achieve the 5bpp quality even though TIFF is lossless.
file size of 2 is likely the same if not bigger than the first case.