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Totally Synthetic by Paul H. Docherty, 25 April 2008

Total Synthesis of Platensimycin


C. H. Kim, K. P. Jang, S. Y. Choi, Y. K. Chung, E. Lee, Angew. Chem. Int. Ed. 2008, 47, 4009-4011.

DOI: 10.1002/anie.200800568

Eun Lee hasn’t bothered with a full total synthesis of the popular target platensimycin, instead satisfying a neat formal synthesis of the right-hand ‘cage’ motif. Key to this was the optimisation of a substrate for a rhodium catalysed carbonyl ylide cycloaddition.

They suggested that a terminal olefin would have the incorrect electronic configuration to lead to the desired product in a [3+2] cycloaddition before attempting the chemistry. However, they did the reaction anyway, and ended out with a astonishing yield of the wrong isomer and only a trace of the desired. With a different HOMO coefficient by using a vinyl halide in place of the terminal olefin, the chemistry proceeded in 83% yield, with only small amounts of the competing products. They then had to remove the extraneous halide using hypophosphite.

All the optimisation of this reaction was performed on racemic material, but their synthesis of enantiopure substrate was quite nice. They took (S)-propylene oxide and opened it with the enolate of isopropyl cyanoacetate. This of course leaves a free hydroxyl anion, which closes onto the isopropyl ester to give the γ-lactone. They then alkylated the intermediate in situ with iodoallyl iodide to give the desired product in pretty decent yield with a d.r. of 5:1. Transformation of this into the key substrate was straight forward.

However, transformation of the cyclisation product into the formal synthesis intermediate was more challenging. An HWE olefination onto the ketone gave an enone in good yield, but reduction of said enone was apparently trying - a hydrosilylation and hydrolysis of the silyl enol ether was required. A few more steps took them to a desired intermediate.