[Thu. 23 Nov. 2017] Prof. Sung-Gon Kim/Department of Chemistry, Kyonggi University, Suwon, Korea

 “Organocatalytic Cascade Reactions for the Asymmetric Synthesis 

of Fused-ring Compounds”

Fused-ring structural units including chroman, indoline, pyrrolidine and hydroqunoline are widely distributed in nature and many biologically active compounds. Molecules containing these structural units exhibit a broad range of bioactivities such as anticancer, antiviral, antitumar, antimicrobial, sex pheromone, and central nervous system activity. Owing to the importance of these class of compounds, the stereoselective synthesis of fused-ring compounds is a noteworthy synthetic goal. In this presentation, we demonstrate the asymmetric synthesis of hydroquinoline, hydroquinazoline, and indolines via catalytic cascade reaction.

First, A synthetic method for the construction of fully substituted enantioenriched 1,4-dihydroquinolines using an organocatalytic aza-Michael/Michael cascade reaction has been developed (Sheme 1). ¹ The asymmetric reaction of 2-(tosylamino)phenyl α,β-unsaturated ketones with alkynyl aldehydes, promoted by diphenylprolinol O-TMS ether as an organocatalyst, generated chiral 1,4-dihydroquinolines in good to high yields with excellent enantioselectivities (up to  97% ee)

We have also found a concise synthetic route to valuable highly functionalized benzosulfamidate-fused tetrahydroquinazoline (Scheme 2).² The [4+2] cycloaddition of o-N-Cbz-amino-b-nitrostyrene with benzoxathiazine 2,2-dioxide using an imidazole as the catalyst afforded tetrahydroquinazolines with high diastereoselectivities. 

In addition, we have established the synthesis of chiral benzosulfamidate-fused pyrrolidines through an Mannich/aza-Michael cascade reaction of δ-formyl-a,b-unsaturated ketones with cyclic N-sulfimines (Scheme 3).³ This simple domino process afforded diverse highly functionalized pyrrolidines in good yields with high diastero- and enantioselectivities.

 Reference

1. Lee, Y.; Heo, S.; Kim, S.-G. Adv. Synth. Catal. 2015, 357, 1545-1550.

2. Sim, J.-T.; Kim, H. Kim, S.-G. Tetrahedron Lett. 2016, 57, 5907-5910.

3. Kim, H.; Kim, Y.; Kim, S.-G. J. Org. Chem. 2017, 82, 8179-8185.