Highly Efficient Synthesis of Spiro[1-azabicyclo[3.2.0]heptane] Frameworks via [3+2]-Cycloaddition
Yulia A. Pronina, Alexander S. Filatov, Stanislav V. Shmakov, Stanislav I. Selivanov, Mariya A. Kryukova, Dar’ya V. Spiridonova, Alexander I. Ponyaev, Alexander V. Stepakov, Vitali M. Boitsov
Abstract
An efficient one-pot three-component [3 + 2]-cycloaddition reaction of azomethine ylides, generated in situ from isatins and azetidine-2-carboxylic acid, with different maleimides and itaconimides has been investigated. These reactions afford the corresponding spiro and dispiro[1-azabicyclo[3.2.0]heptanes] in moderate to high yields (up to 93%) with moderate to excellent diastereoselectivities and excellent regioselectivities under mild conditions. The method provides a simple route to the stereoselective synthesis of new polyheterocyclic systems such as 3-spiro[1-azabicyclo[3.2.0]heptane]oxindoles spiro-conjugated or fused to a succinimide moiety. The observed diastereo- and regioselectivity of cycloaddition reactions is reasoned by DFT studies. The antiproliferative effect of the synthesized compounds against cancer cell lines was assessed.