Synthesis of functionalized 1-azaspirocyclic cyclopentanones using bronsted acid or N-bromosuccinimide promoted ring expansions.
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.
Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z1. gdake@chem.ubc.ca
Gregory R
GR
Dake
Michaël D B
MD
Fenster
Paul B
PB
Hurley
Brian O
BO
Patrick