Oxidative cyclisation of 1,5-dienes by matel oxo agents: synthetic and computational investigations

Abstract

2,5-dihydroxyalkyl substituted tetrahydrofurans (THF-diols) are present in many natural and synthetic products. An efficient approach to THF-diols involves oxidative cyclisation of 1,5-dienes mediated by permanganate ion. The permanganate-promoted oxidative cyclisation of 2-methylenehex-5-enoic acid bearing different aromatic esters was investigated with chiral phase transfer catalyst (CPTC), realising excellent ee’s and yields for the first time as a direct approach. No asymmetric induction was obstained in the absence of aromatic ester group in substrates. Two functional groups, α-naphthyl and 2,3-dichlorophenyl, displayed ee’s in the range of 90%-97%, indicating that the high ee’s can be achieved through a combination of steric and electronic effects where the optimised aryl ester group may achieve a π-stacking interaction with the CPTC. Moderate ee’s were achieved for the majority of aromatic ester substitutions with electron-withdrawing or electron-donating groups, with the exception of the 2,3-dichlorophenyl ester. Enantioinduction was decreased when the electron-rich alkene was substituted with a trans-phenyl group. The CPTC oxidative cyclisation of a 1,5,9-trienoate containing the α-naphthyl group showed a moderate ee and yield.

The reaction mechanism of THF-diol formation from permanganate-mediated and osmium-promoted oxidative cyclisation of 1,5-dienes was studied using high-level DFT simulations ((SMD)-M062X/aug-cc-pVDZ/ECP), showing good agreement with experimental observations, and led to an understanding the key role of acid in promoting the cyclisation step. Ligand exchange with sigma donors such as water and NMO was shown for the FRS intermediate Os(VI) and Mn(V) glycolates. Cyclisation of the protonated Os(VI) dioxoglycolate and Mn(V) glycolate was found to be kinetically and thermodynamically favoured in comparison to other pathways such as reoxidation (Os(VI)Os(VIII) or Mn(V)→Mn(VI)). Although reoxidation of Mn(V)→Mn(VI) was calculated to be disfavoured, decomposition to carbonyl compounds and Mn(IV) was found to be the favoured pathway rather than cyclisation if reoxidation takes place. However, in the absence of acid,
reoxidation of Os(VI)→Os(VIII) was found to be favoured and stimulated a second cycle pathway over cyclisation, as observed experimentally.

Additional insight into the contributory factors was provided by FMO and distortion/interaction energy analysis, in which increasing electrophilicity of the protonated intermediates Os(VI) and Mn(V) glycolates leads to favorable TS interaction energy and attenuated distortion of the tetrahedral Os(VI) and Mn(V) glycolates to deliver the favoured TS’s. An asynchronous (3+2) addition of the O—M—O species, M = Os or Mn, across the alkene double bond with faster development of the C—O[M] bonds compared to C—O[THF] bonds, was obtained by molecular dynamics simulations performed on the SRS. Releasing THF-diol from Mn(III) THF-diolate was found to accessed via acidic disproportionation, whereas for the Os-catalysed reaction, reoxidation of Os(IV) THF-diolate was required to release THF-diol and an Os(VIII) species to complete the catalytic cycle.

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Identifiers

ORCID for Richard C.D. Brown: orcid.org/0000-0003-0156-7087

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