Enantioselective 1,3-Dipolar Cycloadditions of α-Methylene Lactams to Construct Spirocycles
Yuji Nishiura1, Kevin J Gonzalez1, Alexander Q Cusumano1
1The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Abstract:
Spirocyclic scaffolds are important motifs due to their potential to bestow favorable effects on pharmaceutical compounds. However, there is a need for efficient methods for their enantioselective construction. We report a method for the asymmetric 1,3-dipolar cycloaddition of diazoacetates or nitrile oxides with α-methylene lactams to prepare chiral spirocyclic heterocycles. The methodology is high yielding (up to 91% yield) and enantioselective (up to 89% ee) for a wide range of N-substituents and 6- and 7-membered ring lactam substrates.
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