Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds

摘要

In the latest contribution to the “Springer Theses” series, which celebrate outstanding graduate research from the physical sciences, Shinsuke Inuki provides a detailed account of his PhD research, entitled “Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds”. Inuki carried out this work in the laboratory of Professor Hiroaki Ohno (Kyoto University, Japan), whose young research group has established a reputation in the field of late transition metal-catalysed ‘cascade’ organic reactions (also known as ‘domino’ reactions) involving alkynes and allenes. The target audience for the book includes practicing organic chemists with interests in synthesis, and those with specific interests in palladium-catalysed organic reactions, and as such is suited to graduate level and above.As the title suggests, the book delves extensively into mechanistic aspects of palladium-catalysed allene chemistry, with a focus on two reaction types: intramolecular reactions of allenylpalladium(II) complexes with pendant nucleophiles, and intramolecular reactions of allenes activated by pendant palladium(II) species (Scheme I). The key feature of these processes is the ability of the palladium(II) catalyst to enhance the electrophilicity of the allene through coordination to the metal atom in its +2 oxidation state, thus triggering nucleophilic attack. Having established an understanding of each metal-catalysed bicyclisation, Inuki goes on to apply this chemistry to the synthesis of a number of bioactive alkaloid natural products. The overall aims of the work are firstly to extend the state of the art in palladium-activated allene chemistry through a detailed investigation of the influence of substrate stereochemistry on the selectivity and outcome of these reactions, and secondly to demonstrate the utility of this chemistry in the efficient assembly of bioactive natural products. In both respects, the author has certainly succeeded, and delivers an entertaining and informative account of his graduate research.