Synthesis 2005(20): 3571-3580  
DOI: 10.1055/s-2005-918417
PAPER
© Georg Thieme Verlag Stuttgart · New York

Towards the Rubromycins: An Efficient Synthesis of a Suitable Isocoumarin Precursor, its Lactam Analogue, and Palladium-Catalyzed Couplings

Malte Brasholz*, Xiaosong Luan, Hans-Ulrich Reissig
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de;
Further Information

Publication History

Received 18 May 2005
Publication Date:
12 October 2005 (eFirst)

Abstract

6-Iodoisocoumarin 4 and its aza-analogue, 6-iodo-1-oxo-isoquinoline 29, were efficiently prepared from vanillin in seven and six steps, respectively. Key transformations in their syntheses were achieved by directed ortho-lithiation and variations of Horner-Wadsworth-Emmons reactions. Both 6-iodoisocoumarin 4 and its aza-analogue were designed for insertion into syntheses of rubromycin type target structures via palladium-catalyzed coupling reactions. For the isocoumarin subunit, this plan could be confirmed through Heck, Sonogashira, and Suzuki reactions of our building block with various substrates.

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12

Opianic acid (5) was prepared according to ref. 18c.