Unexpected Course of a Mannich Reaction in Alkaloid Synthesis

Unexpected Course of a Mannich Reaction in Alkaloid Synthesis 

In a projected synthesis of the protoberberine alkaloid thalictrifoline 1 the tetrahydroisoquinoline derivative 2 was treated with formaldehyde and acid under a variety of conditions. Unexpectedly, the product was the isoquinobenzoxazepine derivative 3, which was obtained in yields of 70-85% depending on the conditions used. 

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