The reduction of substituted spiro-piperidinyl chromanone oximes with DIBAH reagents has been known to afford the corresponding substituted 4,5-dihydro-3H-spiro[1,5]-benzoxazepine-2,4′-piperidine. The position and electronic effects of the substituents on the aryl moiety control the observed rearrangement. Spiro-benzoxazepine analogue 5j represents a key intermediate for the creation of a library of diverse potential bioactive drugs. With three functional groups that could be selectively and orthogonally protected, many different substituents can be introduced. The obtained analogues were assayed as the possible aspartyl protease inhibitors HIV protease (HIV-1), and β-secretase (BACE-1).