Asymmetric Organocatalytic Cascade Reaction of Aldehydes with 2-Amino-β-nitrostyrenes: Synthesis of Chiral Tetrahydroquinolines and Dihydroquinolines

Abstract

An organocatalytic enantioselective Michael addition/aza-cyclization cascade reaction of aldehydes with 2-amino-β-nitrostyrenes has been developed for the construction of fully substituted chiral tetrahydroquinolines. The reaction, promoted by diphenylprolinol TMS ether as an organocatalyst, generated the chiral tetrahydroquinolines in good to high yield with excellent diastereo- and enantioselectivities (up to >30:1 dr, >99% ee). The method also provided an alternative access to chiral 1,4-dihydroquinolines, which are difficult to synthesize by other methodologies.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Kim and co‐workers reported the synthesis of substituted dihydro‐ ( 69 and 71 ) or tetrahydroquinoline derivatives ( 65 , 66 , and 68 ) with excellent stereoselectivities using asymmetric domino reactions catalyzed by the chiral secondary amine catalyst ( S )‐ 45 . The reaction of the α,β‐unsaturated substrates 64 with malonates 67 , aldehydes 70 , or alkynyl aldehydes 72 led to the formation of compounds 65 , 68 , and 71 , respectively.…”

Nickel(II)‐Catalyzed Diastereo‐ and Enantioselective Michael/ Hemiacetalization Cascade Reaction of α‐Ketoesters with 2‐(2‐Nitrovinyl)phenols

“…Anhydrous dichloromethane was distilled from calcium hydride, anhydrous isopropanol was distilled from calcium oxide, trimethylamine was dried by potassium hydroxide. Diamine ligands, α‐ketoesters, 2‐(2‐nitro‐vinyl)‐phenols, and N ‐PG‐2‐( E )‐(2‐nitrovinyl)aniline were prepared according to the literature procedure.…”

“…Diamine ligands, [13] α-ketoesters, [3a] 2-(2-nitrovinyl)-phenols, [14] and N- 15] were prepared according to the literature procedure. An array of chiral chromane compounds bearing three continuous stereocenters including one all-substituted carbon stereocenter was generally obtained in excellent stereoselectivities (up to > 20:1 dr, > 99% ee).…”

Organocatalyzed C−N bond‐forming Reactions for the Synthesis of Amines and Amides

“…Based on the proposed mechanism and transition state, the attack of the nucleophile was favored from the si-face of nitroolefin to give TS 3 intermediate, which on further cyclization gives tetrahydroquinolines and dihydroquinolines (Scheme 18). [22] Xiao group in 2010 described chiral bifunctional thiourea derived cinchona catalysts XI for the asymmetric aza-Michael-Michael addition of substituted anilines 85 to nitroolefinenoates 86 for the synthesis of polysubstituted 4-aminobenzopyrans 87 with up to 96 % yield, 99 % enatio-and 95 : 5 % dr. Various substituted anilines and nitroolefinenoates were tolerated well and delivered the desired product in good to excellent yield.…”