Synthesis and rearrangement of aminoalkyl lactones to spirocyclic hydroxymethyl lactams

Lithiation of lactones (1) and (2) followed by electrophilic substitution with dibromoalkanes afforded bromoalkyl lactones (3a - 3c) and (4a - 4c). Treatment of 3a, 3b, 4a and 4b with primary amines led to formation of aminoalkyl lactones (5a, 5b, 6a, 6b, and 11), which were rearranged to spirocyclic hydroxyalkyl lactams (7a, 7b, 8a, 8b, and 12). Spirocyclic lactams (7a, 7b, 8a and 8b) were reduced to spirocyclic amines (9a, 9b, 10a and 10b), whereas reduction of lactam (12) gave a separable mixture of amine (13) and tricyclic aminal (15).