Synthesis of Functionalized 1-Azaspirocyclic Cyclopentanones Using Bronsted Acid or <i>N-</i>Bromosuccinimide Promoted Ring Expansions

Azaspirocyclic ring systems are present in a variety of alkaloids. Functionalized 1-azaspirocyclopentanones (<b>6</b>, <b>7</b>, <b>11</b>, <b>12</b>) can be efficiently constructed through semipinacol ring expansion reactions of 2-(1-hydroxycyclobutyl)-<i>p</i>-toluenesulfonylenamides (<b>4</b>) promoted by either a Bronsted acid ((<i>S</i>)-(+)-10-camphorsulfonic acid or HCl) or <i>N</i>-bromosuccinimide, an electrophilic bromine source. Reactions promoted by <i>N</i>-bromosuccinimide tend to proceed in higher yields (80−95%) and with greater diastereoselectivity (3:1−1:0) compared to those reactions promoted by a Bronsted acid. In addition, <i>N</i>-bromosuccinimide promoted reactions can produce a complementary stereochemical outcome compared to the reactions using Bronsted acid.