Concise Synthesis of Multisubstituted Isoquinolines from Pyridines by Regioselective Diels-Alder Reactions of 2-Silyl-3,4-pyridynes

A four‐step regioselective synthesis of multisubstituted isoquinoline derivatives from 3‐bromopyridines was developed by the Diels–Alder (DA) reactions of 2‐silyl‐3,4‐pyridynes with furans, followed by functional‐group transformations. In particular, the silyl group at the C2‐position of the 3,4‐pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1‐position of the isoquinolines by electrophilic ipso‐substitution. A regioselective synthesis of multisubstituted isoquinoline derivatives from 3‐bromopyridines was achieved in four steps, which involved the regioselective Diels–Alder reactions of 3,4‐pyridynes with furans followed by functional group transformations. The regioselectivity of the cycloaddition reaction was attributed to the inductively electron‐donating Si atom at the C2‐position of the 3,4‐pyridyne (see scheme).