Pd-catalyzed enantioselective [4 + 4] dipolar cycloaddition of aliphatic 1,4-dipoles with azadienes to access eight-membered N-heterocycles

Abstract

The construction of eight-membered N-heterocycles with good diastereo- and enantioselective control remains a formidable challenge in asymmetric catalysis. Herein, we report a palladium-catalyzed asymmetric [4 + 4] dipolar cycloaddition of aliphatic 1,4-dipoles with azadienes, furnishing chiral benzofuran- and indene-fused eight-membered N-heterocycles in good yields (up to 86%) and excellent stereoselectivities (up to >20 : 1 dr, 95% ee). This reaction not only represents the first catalytic asymmetric [4 + 4] cyclization of aliphatic 1,4-dipoles but also provides a new and efficient way to construct a variety of novel chiral fused eight-membered N-heterocycles.