Isochromanone synthesis amides

While this method was originally reported in 2002, the true applicability in complex target synthesis has been limited by apparent difficulties resulting from cleavage of the amide residue and the lability of the newly generated benzylic alcohol. Therefore, it was anticipated that considerable effort would have to be invested in applying this approach for isochromanone synthesis. 

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

A related synthetic approach to yohimbine synthesis was utilized by Pandey and his coworkers (Scheme 3.91) (141,142). Thus, isochromanone 518 was converted to bromoester 519 which was then condensed with tryptamine to afford tetracyclic amide 520. Alternatively, 520 could be prepared by treatment of 518 with ammonia to provide 521 which was then AT-tryptophylated. Cyclization of 520 under standard conditions provided the dimethoxy-yohimbane derivative 522. 

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