Catalytic Asymmetric Synthesis of Axially and Centrally Chiral 1,2-Dihydrobenzofuro[3,2-b]pyridines through a [2+2] Cycloaddition/Retroelectrocyclization/Re-Cycloaddition Cascade

A catalytic asymmetric tandem cyclization of azadienes and ortho-alkynylnaphthols accelerated by the chiral N,N '-dioxide-gadolinium(III) complex is disclosed. This method allows the synthesis of a range of 1,2-dihydrobenzofuro[3,2-b]pyridines containing both axially and centrally chiral elements in high yields and excellent stereoselectivities (up to >99% yield, 91:9 dr, 98% ee). A control experiment revealed that this process proceeded through a multistep [2 + 2] cycloaddition/retroelectrocyclization/tautomerism/1,6-conjugate addition cascade.