Experimental and Theoretical Observations on the Intramolecular Nucleophilic Addition of α-Amino Carbanions to Arynes: Synthesis of 1-Aryl-1,2,3,4-tetrahydroisoquinolines

1-Aryl-1,2,3,4-tetrahydroisoquinolines (THIQ) are key intermediates and products in the pharmaceutical industry. A new method involving intramolecular nucleophilic addition of α-amino carbanions to in-situ-generated arynes in N-Boc-protected (Boc = tert-butoxycarbonyl) amine substrates is presented for the synthesis of these compounds. Surprisingly, a similar reaction in Lewis-acid-complexed tertiary amines failed. These results have been analysed using quantum chemical calculations on the intermediates involved in the reactions.

A transition-metal-free and oxidant-free strategy is described for the synthesis of NH and N-Me C-1-arylated 1,2,3,4-tetrahydroisoquinolines.

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