Enantioselective Synthesis of Spiro-bis-N-heterocyclic Lactams via Formal (3+2) Cycloaddition of 3-Methylene
Qian Li1, Peng Han1, Tao Wang1
1Henan Key Laboratory of Natural Medicine Innovation and Transformation, State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng, Henan 475004, P. R. China.
Abstract:
A stereoselective formal (3+2) cycloaddition protocol between 3-methylene isoindolinones and C3-substituted 2-indolylmethanols has been developed. The reactions afforded a wide range of chiral spiro-bis-N-heterocyclic lactams bearing nonadjacent stereocenters, including a quaternary carbon spiro chiral center in good yields (up to 98%) and excellent enantio- and diastereoselectivities (up to >99% ee, >20:1 dr) by chiral phosphoric acid organocatalysis (0.5 mol %). Gram-scale reactions and diversified synthetic transformations of the desired spiro-lactams without loss of stereochemical purity further substantiate their potential utility.
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