Why is difficulty measured in a hash’s leading zeroes? I understand how generating a SHA-256 hash containing any specified sequence requires lots of guessing and checking. The longer the specified sequence, the more rarely that it will appear.

And I understand how inserting random nonces into a block until its hash happens to begin with a certain number of 0s is a computationally expensive and ultimately random process, which demonstrates proof of work.

What I’m wondering is: why zeroes, and why leading?

Could mining work just as feasibly if the challenge were to produce a hash with, say, ends in a certain number of Fs, or has the digits 314159265358979... starting at index 32?

Or is there a technical reason why miners’ goal is to produce a hash which begins with 0s, and not any other character at any other location in the hash?
The "leading zeros" are a simplification. The difficulty is encoded as a target which is essentially a 256 bit number. Since block hashes are produced by SHA-256, they're also a string of 256 bits. If a block candidate's hash interpreted as a number is numerically smaller than the target, the block candidate is a valid block.