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. 2019 Jul 22;24(14):2654.
doi: 10.3390/molecules24142654.

Synthesis of the Core Framework of the Cornexistins by Intramolecular Nozaki-Hiyama-Kishi Coupling

Anthony Aimon  1 , Louis J Farrugia  1 , J Stephen Clark  2
Affiliations

Synthesis of the Core Framework of the Cornexistins by Intramolecular Nozaki-Hiyama-Kishi Coupling

Anthony Aimon et al. Molecules. .

Abstract

A new and direct approach to the construction of the core framework of the herbicidal natural products cornexistin and hydroxycornexistin has been developed. Formation of the nine-membered carbocycle found in the natural products has been accomplished by an intramolecular Nozaki-Hiyama-Kishi reaction between a vinylic iodide and an aldehyde. Good yields of carbocyclic products were obtained from the reaction, but diastereomeric mixtures of allylic alcohols were produced. The cyclisation reaction was successful irrespective of the relative configuration of the stereogenic centres in the cyclisation precursor.

Keywords: Nozaki-Hiyama-Kishi reaction; cornexistins; cyclisation; herbicide; natural product; nine-membered carbocycle; nonadride.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The cornexistin natural products.
Scheme 1
Scheme 1
Retrosynthetic analysis of hydroxycornexistin.
Scheme 2
Scheme 2
Synthesis of the stannylated crotonolactone 4.
Scheme 3
Scheme 3
Synthesis of the chloromethylfuran 12. Reagents and conditions: a n-PrMgCl, THF, –78 °C→rt, 90%; b MnO2, CH2Cl2, reflux, 90%; c Ph3PCH3Br, NaHMDS, THF, 0 °C, 95%; d (i) 9-BBN, THF, 55 °C, (ii) NaOH aq., EtOH, 0 °C, (iii) 30% H2O2, 50 °C, 89%; e t-BuPh2SiCl, Et3N, DMAP, CH2Cl2, rt, 91%; f PPTS, EtOH, 40 °C, 94%; g MeSO2Cl, Et3N, CH2Cl2, rt, 90%.
Scheme 4
Scheme 4
Assembly of the complete carbon backbone by Stille coupling of the vinylic stannane 4 and the chloride 12.
Scheme 5
Scheme 5
Cyclisation of 15a to give the nine-membered ring by use of a Nozaki-Hiyama-Kishi reaction.
Scheme 6
Scheme 6
Cyclisation of 15a to give the nine-membered ring by use of a Nozaki-Hiyama-Kishi reaction and an attempt to improve the diastereomeric ratio by sequential alcohol oxidation and ketone reduction.
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References

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