Stereoselective Mannich reaction catalyzed by tetrahydroindolo[3,2-b]indole under solvent-free conditions

Excellent catalytic stereoselectivity (up to > 99:1) with good yields (up to 88%) for Mannich reaction process under the solvent-free conditions at room temperature has been developed. A series of indole-based organocatalysts (4b,9b-aryl-4b,5,9b,10-tetrahydroindolo[3,2- b ]indole derivatives) ( 2a-2f ) have been designed and synthesized for the three-component direct Mannich reaction of aromatic aldehydes and aromatic amines with ketones. Significantly, the organocatalyst 2a delivered excellent catalytic stereoselectivity (up to >99:1) with good yields (up to 88 %) for above reaction process under the solvent-free conditions at room temperature. X-ray diffraction analysis reveals that organocatalyst 2a is of eight-membered central ring structure with interesting strained quadricyclic ring connectivity. The characteristic rigid V-shape indole ring structure contained in 2a and the formed hydrogen-bonding interaction between 2a and intermediate prefer to the anti-stereoselective product.