Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction
Julian J. Melder, Maxi L. Heldner, Robin Kugler, Levi A. Ziegenhagen, Frank Röminger, Matthias Rudolph, A. Stephen K. Hashmi
Abstract
Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N -aryl-allylamine and homoallylamine derivatives were reacted with sp 3 -hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.