Nitrogen atom insertion into indenes to access isoquinolines

Abstract

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The reaction uses a combination of commercially available phenyliodine(iii) diacetate (PIDA) and ammonium carbamate as the nitrogen source to furnish a wide range of isoquinolines. Various substitution patterns and commonly used functional groups are well tolerated. The operational simplicity renders this protocol broadly applicable and has been successfully extended towards the direct interconversion of cyclopentadienes into the corresponding pyridines. Furthermore, this strategy enables the facile synthesis of ¹⁵N labelled isoquinolines, using ¹⁵NH₄Cl as a commercial ¹⁵N source.

Scheme 1. Context of this work.

Scheme 2. Substrate scope. For the scXRD structures, the ellipsoids are shown at 50% probability and hydrogen atoms are omitted for clarity.^{a 1}H-NMR yield of 0.05-mmol scale crude reaction mixture using 1,1,2,2-tetrachloroethane as the internal standard.^b Isolated yield of a 1.00-mmol scale reaction, conditions: indene (1.0 mmol), PIDA (2.5 mmol), ammonium carbamate (4.0 mmol), methanol (0.07 M), 0 °C for 20 min, then rt for 10 min.

Scheme 3. Isotopically labelled structures. ^aIsolated yields.