Total Synthesis of Jiadifenolide

Total Synthesis of Jiadifenolide

Ian Paterson,* Mengyang Xuan, and Stephen M. Dalby*

DOI: http://dx.doi.org/10.1002/anie.201404224

As promised months ago here is the write-up of the second Jiadifenolide synthesis published this year. The main features of this synthesis from the Paterson group consist of a boron-aldol reaction and a neat SmI2 mediated radical cyclization. Though a racemic synthesis (like in the good old days) this route provides an efficient and highly selective access to Jiadifenolide.

The synthesis started with Luche reduction of cyclopentenone 1 which in turn was treated with mCPBA followed by TBS protection to give oxirane 2. In the presence of BF3 the epoxide rearranged to the corresponding ketone with excellent diastereocontrol. HWE reaction, LiAlH4 reduction and acylation then delivered allyl acetate 5. Silylketene acetal formation and subsequent heating in benzene resulted in Ireland-Claisen rearrangement to yield after another LiAlH4 reduction alcohol 6 in moderate yield. Hydrolysis of the TBS ether and global Swern oxidation finally furnished 7.

Scheme 1

 scheme_1_17102014

The remaining carbon skeleton was attached utilizing the boron enolate of lactone 8 followed by TES protection. Upon treatment with samarium diiodide the last quaternary center was formed giving tricycle 10 in good yield. A possible transition state is depicted below. Deprotection and PCC oxidation then delivered ketone 11. The hydroxyl group at the ring junction was then introduced by a Rubottom oxidation, the ketone subsequently reduced and protected. All that remained was dihydroxylation of the double bond, oxidation to the pyruvate and deprotection of the TES group to complete the synthesis.

 

Scheme 2

 scheme_2_17102014

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