American Chemical Society
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Synthesis of Functionalized 1-Azaspirocyclic Cyclopentanones Using Bronsted Acid or N-Bromosuccinimide Promoted Ring Expansions

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posted on 2004-08-20, 00:00 authored by Gregory R. Dake, Michaël D. B. Fenster, Paul B. Hurley, Brian O. Patrick
Azaspirocyclic ring systems are present in a variety of alkaloids. Functionalized 1-azaspirocyclopentanones (6, 7, 11, 12) can be efficiently constructed through semipinacol ring expansion reactions of 2-(1-hydroxycyclobutyl)-p-toluenesulfonylenamides (4) promoted by either a Bronsted acid ((S)-(+)-10-camphorsulfonic acid or HCl) or N-bromosuccinimide, an electrophilic bromine source. Reactions promoted by N-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, N-bromosuccinimide promoted reactions can produce a complementary stereochemical outcome compared to the reactions using Bronsted acid.