Question

Is the isomer with the largest dipole moment always the least stable? Why stability of isomer decreases with increasing dipole moment?

Answer 1

I haven't heard of a generalization like this, but it makes sense. The polarization of the electron distribution (which is a dipole moment) weakens bonds by withdrawing e density from bonds of less electronegative atoms.

Answer 2

Yes! its true in the case of resonance structures as well. Lets imagine 2 unlike charges (+ve and -ve) separated at a certain distance. They naturally attract each other. In order to separate them to a greater distance (means greater dipole moment) you may need to spend energy or give in energy (endothermic). Its reverse when you bring it closer (exothermic). Thermodynamically, exothermic state is more stable than endothermic states!