Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 19, 2010
Douglass F. Taber
University of Delaware

Synthesis of Naturally-Occurring Cyclic Ethers: Boivivianin B (Murakami), SC-Δ13-9-IsoF (Taber), Brevisamide (Panek, Lindsley, Ghosh), Gambierol (Mori)

The challenge of controlling the relative and absolute configuration of highly substituted cyclic ether-containing natural products continues to stimulate the development of new synthetic methods. Masahiro Murakami of Kyoto University showed (J. Org. Chem. 2009, 74, 6050. DOI: 10.1021/jo900987w) that Rh-mediated addition of an aryl boronic acid to 1 proceeded with high syn diastereocontrol, to give 3. This set the stage for Au-mediated rearrangement, leading to 4. We found (J. Org. Chem. 2009, 74, 5516. DOI: 10.1021/jo900767x) that asymmetric epoxidation of 5 followed by exposure to AD-mix could be used to prepare each of the four diastereomers of 6. We carried 6 on the isofuran 7, using a stereodivergent strategy that allowed the preparation of each of the 32 enantiomerically-pure diastereomers of the natural product.

Following up on the synthesis of Brevisamide 16 described (Complex Cyclic Ethers: (+)-Conocarpan (Hashimoto), (-)-Brevisamide (Satake/Tachibana), (+)-Bruguierol A (Fañanás/Rodríguez), (-)-Berkelic Acid (Snider), and (-)-Aigialomycin D (Harvey) 2009, November 16) by Kazuo Tachibana of the University of Tokyo, three groups reported alternative total syntheses. James S. Panek of Boston University prepared (Org. Lett. 2009, 11, 4390. DOI: 10.1021/ol901801h) the cyclic ether of 16 by addition of the enantiomerically-pure silane 9 to 8. Craig W. Lindsley of Vanderbilt University used (Org. Lett. 2009, 11, 3950. DOI: 10.1021/ol9015755) SmI2 to effect the cyclization of 11 to 12. Arun K. Ghosh of Purdue University employed (Org. Lett. 2009, 11, 4164. DOI: 10.1021/ol901691d) an enantiomerically-pure Cr catalyst to direct the absolute configuration in the hetero Diels-Alder addition of 14 to 13. Rubottom oxidation of the enol ether so formed led to the α-hydroxy ketone 15.

Yuji Mori of Meijo University described (Org. Lett. 2009, 11, 4382. DOI: 10.1021/ol9017408) the total synthesis of the Gambierdiscus toxicus ladder ether Gambierol (19). A key strategy, used repeatedly through the sequence, was the exo cyclization of an epoxy sulfone, illustrated by the conversion of 17 to 18. The epoxy sulfones were prepared by alkylating the anions derived from preformed epoxy sulfones such as 20.

D. F. Taber, Org. Chem. Highlights 2010, April 19.