Stereoselective Synthesis of Hexahydroimidazo[1,2-a]quinolines via S_N2-Type Ring-Opening Hydroarylation–Hydroamination Cascade Cyclization of Activated Aziridines with N-Propargylanilines

Abstract

A novel synthetic approach for the construction of 1,2,3,3a,4,5-hexahydroimidazo­[1,2-a]­quinolines in good yields (up to 75%) with excellent stereoselectivity (dr up to 94:6, ee up to >99%) under one-pot domino ring-opening cyclization (DROC) conditions has been developed. The DROC protocol proceeds through a Lewis acid catalyzed SN2-type ring-opening of activated aziridines with N-propargylanilines followed by intramolecular cyclization comprising concomitant hydroarylation and hydroamination steps in a domino fashion.

Iodine-based reagents in photoredox-organocatalysis

“…70 The functionalization of C(sp 3 )-H bonds of azirine molecules 71 are challenging due to high ring strain and facile ring-opening reactions. 72 Majee and coworkers developed a method for acyloxylation of 2H-azirine molecules using PhI(OAc)2 or PIDA as acyl source under visible light irradiation using organo-photocatalyst (Figure 10). 73 In this study, they concluded that 2 mol % of Rose Bengal (RB) as photocatalyst was good enough for the C(sp 3 )-H acyloxylation of 3-aryl-2H-azirines 26 using 2 equiv of PIDA under blue LED irradiation.…”

Synthesis of Imidazo[2,3‐a]isoquinoline and Imidazo[3,2‐a]quinoline Derivatives with Ynones, Isoquinolines and Quinolines

“…There are only two reported strategies for the general synthesis of imidazoquinolines [10–11] . Ghorai and co‐workers have accomplished a Lewis acid‐catalyzed ring‐expansion with activated aziridines and N ‐propargylaniline for the assembly of imidazoquinoline derivatives [10] . Kutateladze et al have developed a series of straightforward photoassisted reaction systems allowing access to polyheterocyclic molecular architectures [11] .…”

“…However, the synthesis of imidazoquinolines is a much less explored research field. There are only two reported strategies for the general synthesis of imidazoquinolines [10–11] . Ghorai and co‐workers have accomplished a Lewis acid‐catalyzed ring‐expansion with activated aziridines and N ‐propargylaniline for the assembly of imidazoquinoline derivatives [10] .…”

“…[10][11] Ghorai and co-workers have accomplished a Lewis acid-catalyzed ringexpansion with activated aziridines and N-propargylaniline for the assembly of imidazoquinoline derivatives. [10] Kutateladze et al have developed a series of straightforward photoassisted reaction systems allowing access to polyheterocyclic molecular architectures. [11] To the best of our knowledge, there is no report on the synthesis of imidazoquinolines via direct modification of quinolines.…”

“…Beside of extensive study by Cronin and co-workers on the construction of dihydro-imidazo-phenathridiniums, imidazophenathridiniums and related molecules by multistep synthesis, [2] a range of elegant methods have been developed for the synthesis of imidazo[2,3-a]isoquinoline and imidazo[3,2a]quinoline derivatives in the past two decades (Scheme 1). [3][4][5][6][7][8][9][10][11][12] As an intramolecular case, Punniyamurthy et al have developed a simple method for the preparation of tetrahydroimidazo[2,3a]isoquinolines through on water C(sp 3 )-H functionalization/ CÀ O/CÀ N bond formation employing TBAI as a catalyst (eq 1). [3] Intermolecular reactions for the preparation of imidazo[2,3a]isoquinolines always rely on direct modification of isoquinolines and their derivatives.…”