Towards a general diastereoselective route to oxabicyclo[3.2.1]octanes via a gold-catalysed cascade reaction.

Fu, Junkai; Gu, Yueqing; Yuan, Hao; Luo, Tuoping; Liu, Song; Lan, Yu; Gong, Jianxian; Yang, Zhen · Nat Commun · 2015

basic_science · Level V

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Abstract

The development of an efficient diastereoselective synthesis of the oxabicyclo[3.2.1]octane ring system bearing two oxygenated quaternary chiral centres represents a significant challenge. This motif can be found in a wide range of natural products with significant biological activities. Here we report the synthesis of such kind of scaffold using a cyclohexane-trans-1,4-diol with an alkyne side chain in the presence of Au(I) catalyst. This is a domino process in which two C-H, two C-O and one C-C bond is assembled through a sequence of cyclization/semi-pinacol rearrangements. This strategy has been successfully applied to the asymmetric formal total synthesis of (+)-cortistatins.