Attachment of ketide side chains on methyl-1,4-naphthoquinones for biomimetic type angucycline syntheses

The Michael addition of nucleophiles 5-10 derived from beta-ketoesters with the methyl-1,4-naphthoquinones 16 and 20 was systematically investigated in connection with a biomimetic type synthesis of angucyclinone antibiotics. Drawbacks of these reactions were the formation of regioisomers (e.g. 12/13 and 18/19), unwanted cyclizations (14 and 15), and occasional 1,2-addition (23). No side reactions and a good overall yield (80%) in the attachment of a C-3-2-oxoside chain was achieved by Stille reaction of allyl stannane 11 with the bromoquinone 24 followed by cleavage of the double bond to yield ketone 26.