Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium Ion Formation-Fragmentations: Computational Modelling and Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C and Marilzabicycloallene D

DOI: 10.14469/hpc/1116 Metadata

Created: 2016-07-26 16:14

Last modified: 2017-09-13 07:47

Author: Henry Rzepa

Co-author: Andrew White
Co-author: D. Christopher Braddock
Co-author: James Clarke
Co-author: Karl Bonney
Co-author: Muhammad Yaqoob
Co-author: Savade Solanki

The total synthesis of 12-epoxyobtusallene IV, 12-epoxyobtusallene II, obtusallene X, marilzabicycloallene C and marilzabicycloallene D as halogenated C15-acetogenin twelve-membered bicyclic and tricyclic ether bromoallene-containing marine metabolites from Laurencia species are described. Two enantiomerically pure C4-epimeric dioxabicyclo[8.2.1]tridecenes were synthesised by E-selective ring-closing metathesis where their absolute stereochemistry was previously set via catalytic asymmetric homoallylic epoxidation and elaborated via regioselective epoxide-ring opening and diastereoselective bromoetherification. Epimeric face-selective oxidation of their 12,13 olefins followed by bromoallene installation allowed access to the oppositely configured 12,13-epoxides of 12-epoxyobtusallene II & 12-epoxyobtusallene IV. Subsequent exploration of their putative biomimetic oxonium ion formation-fragmentations reactions revealed diastereodivergent pathways giving marilzabicycloallene C and obtusallene X respectively. The original configurations of the substrates evidently control oxonium ion formation and their subsequent preferred mode of fragmentation by nucleophilic attack at C9 or C12. Quantum modelling of this stereoselectivity at the B97X-D/Def2-TZVPPD/SCRF=methanol level revealed that in addition to direction resulting from hydrogen bonding, the dipole moment of the ion-pair transition state is an important factor. Marilzabicycloallene D as a pentahalogenated twelve-membered bicyclic ether bromoallene was synthesised by a face-selective chloronium ion initiated oxonium ion formation-fragmentation process followed by subsequent bromoallene installation.

Members

DOIDescription
10.14469/hpc/1267 NMR data for Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium Ion Formation-Fragmentations: Computational Modelling and Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C and Marilzabicycloallene D
10.14469/hpc/1919 Computational data for Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium Ion Formation-Fragmentations: Computational Modelling and Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C and Marilzabicycloallene D
10.14469/hpc/1248 FAIR Data table. Computed relative reaction free energies (kcal/mol-1) of Obtusallene derived oxonium and chloronium cations
10.14469/hpc/678 12: x-ray conformation methanol TS Def2-TZVPPD BF4 ion pair, top face

Associated DOIs

DOIDescription
10.1021/acs.joc.6b02008 Article corresponding to these data.
10.14469/ch/191973 12R-B calculated NBO analysis. Conformation taken from doi: 10.5517/ccxfjd7. Def2-TZVPPD cation only.
10.14469/ch/191976 oxonium cation 9...Br x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/191978 oxonium cation 6...Br x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/191979 oxonium cation 12...Br x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/191985 9...OMe x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/191986 12...OMe x-ray conformation methanol TS Def2-TZVPPD freq
10.14469/ch/191988 6...OMe x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/191997 12...HOMe x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/192008 9...HOMe alt conformation methanol TS Def2-TZVPPD
10.14469/ch/192018 6...HOMe x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/192018 6...HOMe x-ray conformation methanol TS Def2-TZVPPD
10.14469/ch/192024 9...HOMe X-ray conformation methanol TS Def2-TZVPPD

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