Benzyl ethers benzyne

Dibenzopyrrocolines have been prepared by intramolecular addition of benzyne intermediates and by nucleophilic substitutions, as shown in Scheme 6 with the synthesis of ( )-cryptowoline (2) and the related dehydro base 39 by Bennington and Morin (7). ( )-6 -Bromotetrahydroisoquinoline 37, prepared by standard procedures, when heated with copper powder in dimethylformamide afforded dibenzopyrrocoline 38 in low yield, and 39 was formed when 37 was allowed to react with potassium amide in liquid ammonia. Compound 39 was converted to ( )-cryptowoline iodide (2) by hydrogenolysis of O-benzyl ether 39 and quartemization with methyl iodide. 

The benzyne route to dibenzopyrrocoline alkaloids with the 1-benzyltetrahy-droisoquinolines (40) listed in Table II was investigated by Kametani et al. (28), Kessar et al. (29), and Gibson and Ahmed (31). Secondary amines protected as 7-0-benzyl ethers, affording unstable tetrahydro intermediates with benzyl ether functions difficult to deprotect, were less favored than the corresponding N-methyl-substituted analogs, affording the desired quartemary alkaloids directly. 

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