Ru-catalysed oxidative cyclisation of 1,5-dienes: an unprecedented role for the co-oxidant

Abstract

The Ru-mediated oxidative cyclisation of 1,5-dienes to furnish 2,5-dihydroxyalkyl-substituted tetrahydrofuran-diols (THF-diols) represents a practical approach for the synthesis of many bioactive natural products. In the current study, we reported profound findings obtained by density functional theory (DFT) simulations, and they were consistent with the experimental conditions. The results set out a catalytic cycle within intermediacy of NaIO₄-complexed Ru(VI) species. Importantly, the co-oxidant played a critical role in the cyclisation step and subsequently the release of THF-diols. Following the formation of Ru(VI) glycolate, cyclisation and THF-diol release proceeded through NaIO₄-coordinated Ru(VI) intermediates, outpacing the Ru(VIII) glycolate or THF-diolate intermediates and subsequently entering “second cycle” type pathways. The results indicated a cycle involving Ru(VIII)/Ru(VI)/Ru(IV)/Ru(VI) rather than Ru(VIII)/Ru(VI)/Ru(VIII)/Ru(VI)/Ru(VIII). Additionally, the existence of an electron-withdrawing group (EWG) on one of the double bonds of 1,5-dienes revealed that the regioselectivity of the Ru-catalysed oxidative cyclisation was predominantly initiated at the electron-rich alkene. Overall, this study offers new insights, which were ignored by earlier experimentalists and theoreticians, into the Ru-catalysed functionalizations of alkenes and 1,5-dienes.

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Introduction

Many bioactive natural products such as polyether ionophore antibiotics and annonaceous acetogenins contain THF-diols.^1,2 An important approach for the synthesis of THF-diols is the oxidative cyclisation of 1,5-dienes using transition-metal–oxo species (MnO₄⁻, OsO₄, and RuO₄). This approach has been shown to give structurally complex products,³ whereby up to four stereogenic centres can be formed with the control of relative stereochemistry in a single reaction.^3–8 The synthesis of cis-THF-diols by the oxidative cyclisation of 1,5-dienes was first reported using potassium permanganate,⁹ which was followed by related stereoselective approaches using osmium and ruthenium.^10,11 The first mechanistic proposal was set out for the permanganate-promoted reaction by Walba et al. and was based on the (2 + 2) suprafacial additions of metal–oxo species across the olefin double bonds. Baldwin proposed an alternative mechanism for Mn oxidative cyclisations based on (3 + 2) cycloadditions,^6c,9a,12,13 which has become a general framework for oxidative cyclisations by Os and Ru–oxo species,^3,10,11 and the Ru-catalysed version is the concern of this paper.¹⁴

Previous studies on the RuO₄ oxidative cyclisation of 1,5-dienes have reported mixtures of cis and trans THF-diol products.^11a However, developments by Stark et al. led to cis-THF diols with high yields and stereoselectivities (Scheme 1).^5b,11b,11d They suggested a mechanism analogous to the one presented by Baldwin.^9a It is basically believed that RuO₄ interacts with a double bond to form Ru(VI) glycolate 3, followed by cyclisation to give THF-diolate Ru(IV) 4 and subsequent hydrolysis to afford cis-THF-diol 2 (Scheme 1).

Scheme 1 Ru-mediated oxidative cyclisation of 1,5-diene 1 to afford cis-THF-diol 2.

Mechanistic computational studies on the oxidative cyclisation of 1,5-dienes by metal–oxo species have been reported, but studies concerning Ru-mediated reactions have not been fully investigated.^13,15 Despite the reliable use of the reaction in the synthetic methods,^11,14 only one step of the catalytic cycle, which is alkene oxidation to yield Ru(VI) dioxoglycolate, has been studied computationally.¹⁶ The mechanism of Ru-catalysed oxidative cyclisation involves several steps. These steps are as follows:

(a) alkene oxidation to generate Ru(VI) glycolate (the first reaction step, FRS);¹⁶

(b) cyclisation to form the Ru(IV) THF-diolate (the second reaction step, SRS);

(c) possible secondary reactions that may occur prior to cyclisation such as reoxidation, complexation with a co-oxidant, and hydration with water;

(d) hydrolysis to release the THF-diol; and

(e) other intermolecular (3 + 2) cycloaddition pathways that propagate the catalytic cycle (Fig. 1).

Fig. 1 Pathways obtained for the Ru-catalysed oxidative cyclisation of 1,5-diene (5) in this study.

In this context, almost no details of the mechanism's steps have appeared in the literature. This lack of mechanistic understanding frequently impedes further improvements in the catalytic studies. Therefore, the present study reports a detailed description of these steps, which were ignored by previous researchers, both experimentalists and theoreticians, using computational investigations. Based on the results, we proposed a catalytic cycle and determined the important role of the co-oxidant in the Ru-catalysed oxidative cyclisation of 1,5-dienes. Subsequently, the regioselectivity of the reaction was evaluated when an EWG was found on one of the double bonds of 1,5-dienes.

Results and discussion

The computational approach to the oxidative cyclisation of 1,5-diene was performed using DFT simulations with the (SMD/THF)-M06/aug-cc-pVDZ/LANL2DZ//M06/cc-pVDZ/LANL2DZ level of theory at 298.15 K.¹⁷ All calculations considered here account for singlet spin multiplicity.¹⁸ The following sections explain the mechanism of Ru-catalysed oxidative cyclisation and the regioselectivity of the reaction.

Mechanism of Ru-catalysed oxidative cyclisation

The formation of THF-diolate from the oxidative cyclisation of 1,5-diene (5) has been realised through different reaction manifolds considered for SRS after the formation of the Ru(VI) dioxoglycolate intermediate 7 (Fig. 2). Generally, these manifolds either proceed without or with a co-oxidant (NaIO₄).

Fig. 2 Free energy profiles for the oxidative cyclisation of 1,5-diene 5 by RuO₄, showing cyclisation pathways without water (7 → 9) and with water (7_H2O → 9_H2O).

Oxidative cyclisation without a co-oxidant. The simplest pathway to form THF-diolate 9 was estimated without considering a co-oxidant (Fig. 2). Initially, the reaction of RuO₄ with the double bond of 1,5-diene (5) needed a remarkably low barrier of only 3.2 kcal mol⁻¹ through a tetrahedral (3 + 2) cycloaddition TS 6 to give a distorted tetrahedral Ru(VI) ruthenate ester 7 via a highly exergonic step (ΔG_r = −58.2 kcal mol⁻¹).^19,20 Without any additive, this intermediate dynamically cyclised to the square planar Ru(IV) diolate 9 (ΔG_r = −37.8 kcal mol⁻¹) through a tetrahedral (3 + 2) cycloaddition TS 8 with a barrier of 9.4 kcal mol⁻¹.^21–23 Other possible pathways from Ru(VI) 7 are the addition of water (blue pathway, Fig. 2) and NaIO₄ or reoxidation (Fig. 3).

Fig. 3 Free energy profiles for the Ru(VIII) (right) and NaIO₄-complexed Ru(VI) (left) cyclisation pathways.

The addition of a water molecule stabilized Ru(VI) 7 by 5.2 kcal mol⁻¹ to give a distorted square pyramid Ru(VI) glycolate 7_H2O (Fig. 2, blue pathway). However, this raised the barrier of cyclisation to 13.6 kcal mol⁻¹ via a distorted trigonal bipyramidal (3 + 2) cycloaddition TS 8_H2O to form the trigonal bipyramidal Ru(IV) diolate 9_H2O (ΔG_r = −35.2 kcal mol⁻¹). The increased energy barrier can be understood by the effect of the decrease in the electrophilicity of the hydrated Ru(VI) glycolate 7_H2O (see Fig. 4). The LUMO energy of 7_H2O (LUMO = −3.7 eV, E_gap = 3.1 eV) has been calculated to be higher than that of the non-hydrated Ru(VI) 7 (LUMO = −4.2 eV, E_gap = 2.6 eV). The HOMO and LUMO orbitals are shown in Fig. 4.

Fig. 4 Visualization (0.02 isovalue surface) of the HOMO (located on the alkene site) and LUMO (located on the Ru site) orbitals of Ru(VI) 7, 7_H2O, and 7_NaIO4 and Ru(VIII) 7_[ox] glycolates during the oxidative cyclisation of 1,5-diene (5) by RuO₄.

Oxidative cyclisation with a co-oxidant. Now, the addition of NaIO₄ to Ru(VI) 7 forms the NaIO₄-complexed Ru(VI) glycolate 7_NaIO4, which is either cyclised or reoxidized, Ru(VI) → Ru(VIII) (see Fig. 3). The effect of reoxidation Ru(VI) → Ru(VIII) on oxidative cyclisation was considered first through oxo-ligand transfer from NaIO₄ to Ru(VI) dioxoglycolate (right, Fig. 3). The TS of reoxidation was investigated as two elementary steps, which are NaIO₄–Ru(VI) complexation and oxo-transfer dissociation, and in an inner sphere manner.^24,25 The formation of NaIO₄-complexed Ru(VI) 7_NaIO4 was exergonic by 6.3 kcal mol⁻¹ and preceded the dissociation of the I–O bond to release Ru(VIII) trioxoglycolate and NaIO₃ with a high energy barrier of 39.5 kcal mol⁻¹ via TS 10 as an endergonic step (ΔG_r = 16.0 kcal mol⁻¹). Although the barrier of reoxidation is unfavourable, it was found that once 7_[ox] was formed, Ru(VI) THF-diolate 9_[ox] was directly generated through a barrierless and thermodynamic sink step (TS 8_[ox], ΔG^‡ 0.5 and ΔG_r = −64.5 kcal mol⁻¹).

A comparison between Ru(VIII), hydrated Ru(VI), and naked Ru(VI) cyclisation is clearly evident. The Ru(VI) glycolates 7 and 7_H2O have two d electrons, and these can lead to electronic repulsions with the two oxo ligands.²⁶ Consequently, this will decrease the electrophilicity and increase the cyclisation barrier. In contrast, this does not occur in 7_[ox] and thus, a remarkable increase in the electrophilicity (LUMO = −4.6 eV, E_gap = 2.2 eV, Fig. 4) is seen to stimulate barrierless cycloaddition.

It is noteworthy to mention that reoxidation may be competitive when only alkenes are applied and not 1,5-dienes. However, whether the Ru(VIII) intermediate is viable during the Ru-catalysed dihydroxylation of alkenes is still disputed.²⁷ In this work, DFT simulations showed that reoxidation was excluded due to the high barrier needed. Therefore, there is no possibility of entering a “second cycle” type pathway from the reaction of 7_[ox] with another alkene to obtain the Ru(IV) bisglycolate (see Fig. 1).^{4c,11f,28–30}

Cyclisation through NaIO₄-complexed Ru(VI) glycolate displayed a low barrier of 2.5 kcal mol⁻¹ via distorted trigonal bipyramidal TS 8_NaIO4 and was a favourably exergonic step with ΔG_r = −43.1 kcal mol⁻¹ (Fig. 3, right).³¹ When the NaIO₄-complexed pathway (7_NaIO4 → 8_NaIO4 → 9_NaIO4) and the reoxidation pathway (7_NaIO4 → 7_[ox] → 8_[ox] → 9_[ox]) were compared, the former was exceedingly preferred. Molecular orbital analysis revealed that although the energy gap for 7_NaIO4 was 2.7 eV (Fig. 4), which was slightly lower than that for 7, its TS 8_NaIO4 had a significantly lower barrier. This may be attributed to the favourable interactions between the reacting moieties with less geometrical changes or reorganizations around the Ru centre due to the exchangeable oxo ligands between the I and Ru centres that lead to a more stabilized TS to give Ru(IV) THF-diolate 9_NaIO4. The calculations show that Ru(IV) THF-diolate 9_NaIO4 is simultaneously dissociated to Ru(VI) dioxodiolate 9_[ox] in a favoured step (ΔG_r = −6.6 kcal mol⁻¹) (Fig. 3, right).

In summary, in the presence of NaIO₄, cyclisation through NaIO₄-coordinated Ru(VI) glycolate 7_NaIO4 outpaces cyclisation via hydrated Ru(VI) 7_H2O and reoxidized Ru(VIII) 7_[ox]. In this regard, the simulations showed that reoxidation was energetically unfavourable and thus, the formation of a “second cycle” type pathway product, Ru(VI) bisglycolate, was totally outpaced.

THF-diol release. The calculations reported above support the cyclisation of periodate-complexed Ru(VI) to give an Ru(IV) THF-diolate product. The completion of a catalytic cycle to furnish THF-diol 15 and regenerate a Ru(VIII) species capable of propagating ruthenylation is important. Now, the Ru(VI) dioxodiolate 9_[ox] entails pathways toward either oxidation/hydrolysis or hydrolysis/oxidation while bearing in mind that 9_[ox] can engage in the ruthenylation of another 1,5-diene molecule (Fig. 5).

Fig. 5 Free energy evaluations for divergent reactions of 9_[ox], showing hydrolysis via Ru(VI) or Ru(VIII) or entering a second cycle through another ruthenylation. E-But-2-ene was used as a model for 5 to reduce the computational cost.

First, the oxidation of Ru(IV) THF-dioxodiolate 9_[ox] to Ru(VIII) trioxodiolate 9_[ox][ox] is considered with an overall endergonicity of 13.5 kcal mol⁻¹ (Fig. 5, blue pathway).³² In this regard, Ru(VIII) THF-trioxodiolate 9_[ox][ox] can overcome a barrier of 21.1 kcal mol⁻¹ via TS 12 to break the first O–[Ru] diolate in a modestly exergonic step (ΔG_r = −6.5 kcal mol⁻¹, see 13, Fig. 5), which is followed by the release of THF-diol 15 as an overall exergonic hydrolysis pathway (ΔG_r = −20.9 kcal mol⁻¹). Instead, DFT simulations indicate that Ru(VI) THF-dioxodiolate 9_[ox] coordinates with NaIO₄ and then H₂O to yield 16 via a low endergonic step (ΔG_r = 3.4 kcal mol⁻¹, Fig. 5). Also, 16 needs a comparatively low barrier of 10.7 kcal mol⁻¹ via a TS 17 to give intermediate 18 via an exergonic process (ΔG_r = −3.4 kcal mol⁻¹). In the opposite mode to the hydrolysis of Ru(VIII), the hydrolysis of the second O–[Ru] diolate in intermediate 18 was calculated to be unfavourable when compared to the experimental conditions. The located TS 22, shown in ESI Fig. 4,† requires a high energy barrier of 21.7 kcal mol⁻¹ to transfer the proton from the oxo ligand (HO–[Ru]) to the second O–[Ru] diolate bond although it is an exergonic step (ΔG_r = −7.6 kcal mol⁻¹). Obviously, proton transfers involving electronegative atoms are known to be fast and diffusion controlled and therefore, getting intermediate 19 via a slightly endergonic step (ΔG_r = 6.3 kcal mol⁻¹) is suggested. At this point, hydrolysis through Ru(VI) followed by oxidation to regenerate RuO₄ is more accessible than reoxidation, i.e., Ru(VI) → Ru(VIII) followed by hydrolysis.

Second, it is interesting to note that Ru(VI) dioxodiolate 9_[ox] is a competent ruthenylating agent in the hydrolysis pathway and is capable of reacting with another alkene via a so-called “second cycle” type pathway (Fig. 5, left pathway).³³ The energy barrier of the (3 + 2) cycloaddition of 9_[ox] with E-but-2-ene was found to be 15.4 kcal mol⁻¹ via TS 19 to afford a tetraester 20 via an exergonic reaction (ΔG_r = −50.5 kcal mol⁻¹). This would reveal a barrier difference of 1.3 kcal mol⁻¹ between intermolecular ruthenylation and hydrolysis with the hydrolysis being predominant.

Finally, based on the above-mentioned results, a catalytic cycle for the Ru-catalysed oxidative cyclisation of 1,5-diene 5 was proposed (Fig. 6). The complexation of Ru(VI) glycolate 7 with a co-oxidant (NaIO₄) is an essential feature found for SRS. The reoxidation of NaIO₄-coordinated Ru(IV) THF-diolate 9_NaIO4 to Ru(VI) THF-dioxodiolate 9_[ox] followed by another coordination with both water and NaIO₄ gives 17, releasing its THF-diol 15 and regenerating RuO₄ to continue the iterative cycle.

Fig. 6 Proposed catalytic cycle for Ru-catalysed oxidative cyclisation of 1,5-diene 5.

Regioselectivity of the Ru-catalysed oxidative cyclisation

The regioselectivity of RuO₄ is considered when an EWG such as a methyl ester group is found on one of the double bonds of 1,5-diene, as indicated in methyl dienoate 5a shown in Fig. 7.^11b Based on the aforementioned findings, DFT calculations have been performed for FRS and SRS (Fig. 7). For FRS, the favourability of RuO₄ to initiate the electron-rich alkene (ERA) pathway over the electron-deficient alkene (EDA) pathway is highly evident. For instance, the ERA Ru(VI) glycolate 7a (ΔG_r = −62.4 kcal mol⁻¹) is formed via a barrierless (3 + 2) cycloaddition TS 6a of ΔG^‡ = 1.7 kcal mol⁻¹ (Fig. 7, right), whereas the formation of the EDA Ru(VI) glycolate d-7a requires a higher barrier of 4.9 kcal mol⁻¹ via TS d-6a via a slightly less exergonic step (ΔG_r = −55.1 kcal mol⁻¹ (Fig. 7, left).³⁴ Thus, the ERA product is kinetically (ΔΔG^‡ = −3.2 kcal mol⁻¹) and thermodynamically (ΔΔG_r = −7.3 kcal mol⁻¹) favoured with a greater development of the C–O bond formation for ERA TS 6a over EDA TS d-6a.

Fig. 7 Free energy bifurcation for the regioselectivity of the Ru-catalyzed oxidative cyclisation of methyl 1,5-dienoate (5a) initiated at the electron-rich and electron-deficient alkenes.

On the cyclisation step, the ERA Ru(VI) glycolate 7a_NaIO4 cyclises, via TS 8a_NaIO4 with a barrier of ΔG^‡ = 8.6 kcal mol⁻¹, and this is slower than cyclisation through EDA Ru(VI) glycolate pathway (TS d-8a_NaIO4, ΔG^‡ = 1.5 kcal mol⁻¹). A reasonable explanation for this is that the oxo ligands in d-7a_NaIO4 are more electrophilic than those in 7a_NaIO4 mainly due to the electron-withdrawing nature of the carbonyl group with a possible minor contribution from complexation with NaIO₄. This would lead to a lower barrier for cyclisation because it has lower LUMO energy on the Ru site and higher HOMO energy on the alkene site. However, in the ERA Ru(VI) glycolate 7a_NaIO4, cyclisation occurs from the highly electron-deficient alkene site to the slightly electron-deficient Ru site, subsequently ensuring that the cyclisation has a higher barrier. In comparison with the symmetric 1,5-diene (5), the cyclisation via the ERA NaIO₄-complexed Ru(VI) glycolate requires a three-fold higher energy barrier than the cyclisation with the symmetric 1,5-diene (5). Overall, the existence of an EWG on one of the alkenes in the 1,5-diene structure results in the Ru-catalysed oxidative cyclisation being predominantly initiated at the electron-rich alkene.

Conclusions

The first detailed mechanistic study on the Ru-catalysed oxidative cyclisation of 1,5-dienes has been performed with the (SMD/THF)-M06/aug-cc-pVDZ/LANL2DZ//M06/cc-pVDZ/LANL2DZ level of theory. The DFT simulations are in excellent agreement with the experimental conditions and consequently, complications accompanied throughout the Ru-catalysed oxidative cyclisation of 1,5-dienes are resolved.

The results set out the catalytic cycle for THF-diol formation through the intermediacy of Ru(VI) with RuO₄ as the active catalytic species. Importantly, the co-oxidant NaIO₄ has been evidently shown to play a critical role in the cyclisation and hydrolysis steps through complexation with Ru rather than reoxidation to a higher oxidation state. Following the initially formed Ru(VI) dioxoglycolate, the cyclisation overcomes a favourable NaIO₄-coordinated TS to give the THF-diolate ring, excluding the cyclisation or entering the second cycle through the intermediacy of Ru(VIII) trioxoglycolate 7_[ox]. Thereafter, the dissociation of the NaIO₄-coordinated Ru(IV) THF-diolate 9_NaIO4 to Ru(VI) THF-dioxodiolate 9_[ox] was calculated to undergo hydrolytic release to give THF-diol 15 and RuO₄ to continue the iterative cycle. The release of THF-diol 15 from Ru(VI) THF-dioxodiolate 9_[ox] was found to be favourable over reoxidation to Ru(VIII) THF-trioxodiolate 9_[ox][ox] or entering the so-called “second cycle” type pathway. This protocol has evidently conducted a cycle of Ru(VIII)/Ru(VI)/Ru(IV)/Ru(VI) rather than Ru(VIII)/Ru(VI)/Ru(VIII)/Ru(VI)/Ru(VIII).

Furthermore, DFT simulations on asymmetric 1,5-dienes, such as methyl 1,5-dienoate (5a), have provided further mechanistic descriptions when an electron-withdrawing group is attached to one of the alkenes. The calculations revealed that the Ru-catalysed oxidative cyclisation is predominantly initiated at the electron-rich alkene. The cyclisation from the ERA NaIO₄-complexed Ru(VI) glycolate was shown to be slower than the cyclisation from an electron-deficient Ru(VI) intermediate. In comparison with symmetric 1,5-diene (5), the barrier for cyclisation from an asymmetric 1,5-diene was calculated to be more than three times higher than the barrier for symmetric cyclisation.

Overall, this computational study gives significantly important insights into this key synthetic method, which may offer a viable pathway towards advancing an efficient protocol for alkene oxidation.

Computational details

All calculations were performed using Gaussian 09 (ref. 35) with the global hybrid functional approximations M06 (ref. 36) used with the augmented correlation-consistent polarized valence double-ζ (DZ) basis set (cc-pVDZ and aug-cc-pVDZ)³⁷ for C, H, O, Si, and Na, whereas an effective core potential basis step LANL2DZ³⁸ was used for Ru and I. All geometry optimisations, even for triplet and quintet spin multiplicities, shown in the ESI,† were performed with the basis set cc-pVDZ/LANL2DZ, in which all minima intermediates were verified by the absence of negative eigenvalues in the vibrational frequency analysis. Restricted spin Hartree–Fock calculations were used for singlet spin multiplicity, whereas unrestricted spin calculations were used for triplet and quintet spin multiplicity. All of the transition state structures were found using the Berny algorithm,³⁹ verified by vibrational analysis, and visualised by animating the negative eigenvector coordinate. In order to account for the effect of the solvent, single-point energies of the optimised geometries were evaluated with the M06/aug-cc-pVDZ/LANL2DZ level of theory in tetrahydrofuran (THF) as a representative solvent medium via the solvation model based on density (IEFPCM-SMD).⁴⁰ To obtain the free energies at 298.15 K and 1 atm, the thermal corrections were evaluated from the unscaled vibrational frequencies at the M06/cc-pVDZ/LANL2DZ level of theory and were then added to the electronic energies calculated from the M06/aug-cc-pVDZ/LANL2DZ level of theory. Intrinsic reaction coordinate (IRC) calculations were performed for the identified transition states to confirm the reaction path proceeding in both directions (reactant and product), in which the Hessian was recomputed every 3 predictor steps with a step size along the reaction path of 0.05 Bohr.⁴¹ All activation free energies are quoted relative to infinitely separated reagents and the optimised structures were illustrated using CYLview.⁴²

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

I acknowledge the computational resources from the iridis4 supercomputer supported by the University of Southampton. I highly acknowledge the University of Southampton/School of Chemistry for providing the visitor-status research position (2717441/EB00-VISIT). Many thanks to Prof. Richard C. D. Brown for his valuable proofreading and his precious support.

Notes and references

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5. For other oxidative cyclisations of 1,4-dienes, 1,6-dienes and 1,7-dienes see: (a) V. Piccialli, N. Borbone and G. Oliviero, Ruthenium-catalysed oxidative cyclisation of 1,7-dienes. A novel diastereoselective synthesis of 2,7-disubstituted trans-oxepane diols, Tetrahedron Lett., 2007, 48, 5131–5135; (b) S. Roth and C. B. W. Stark, Efficient oxidative cyclisation of 1,6-dienes: a highly diastereoselective entry to substituted tetrahydropyrans, Angew. Chem., Int. Ed., 2006, 45, 6218–6221; (c) A. R. L. Cecil and R. C. D. Brown, Stereoselective synthesis of cis-2,6-bis-hydroxyalkyl-tetrahydropyrans by the permanganate promoted oxidative cyclisation of 1,6-dienes, Tetrahedron Lett., 2004, 45, 7269–7271; (d) B. Travis and B. Borhan, Oxidative cyclisation of 1,4-dienes to yield 2,3,5-trisubstituted tetrahydrofuran-diols, Tetrahedron Lett., 2001, 42, 7741–7745; (e) V. Piccialli, RuO₄-catalysed oxidative cyclisation of 1,6-dienes to trans-2,6-bis(hydroxymethyl)tetrahydropyranyldiols. A novel stereoselective process, Tetrahedron Lett., 2000, 41, 3731–3733.
6. (a) A. M. Al Hazmi, N. S. Sheikh, C. J. R. Bataille, A. A. M. Al-Hadedi, S. V. Watkin, T. J. Luker, N. P. Camp and R. C. D. Brown, trans-2-Tritylcyclohexanol as a chiral auxiliary in permanganate-mediated oxidative cyclisation of 2-methylenehept-5-enoates: application to the synthesis of trans-(+)-linalool oxide, Org. Lett., 2014, 16, 5104–5107; (b) R. C. D. Brown and P. J. Kocienski, A synthesis of salinomycin 1. Synthesis of key fragments, Synlett, 1994, 415–417; (c) D. M. Walba, M. D. Wand and M. C. Wilkes, Stereochemistry of the permanganate oxidation of 1,5-dienes, J. Am. Chem. Soc., 1979, 101, 4396–4397.
7. R. C. D. Brown and J. F. Keily, Asymmetric permanganate-promoted oxidative cyclisation of 1,5-dienes by using chiral phase-transfer catalysis, Angew. Chem., Int. Ed., 2001, 40, 4496–4498.
8. For cis-selective THF-diol formation from oxidative cyclisation of dihydroxyalkenes using metal oxo agents (Ru, Os, and Cr). For Ru oxo-species: (a) H. Cheng and C. B. W. Stark, A double donor-activated ruthenium(VII) catalyst: synthesis of enantiomerically pure THF-diols, Angew. Chem., Int. Ed., 2010, 49, 1587–1590; (b) S. Gohler and C. B. W. Stark, Catalytic diastereo- and position selective oxidative mono-cyclisation of 1,5,9-trienes and polyenes, Org. Biomol. Chem., 2007, 5, 1605–1614Os oxo-species: (c) T. J. Donohoe, K. M. P. Wheelhouse, P. J. Lindsay-Scott, P. A. Glossop, I. A. Nash and J. S. Parker, Pyridine-N-oxide as a mild reoxidant which transforms osmium-catalysed oxidative cyclisation, Angew. Chem., Int. Ed., 2008, 47, 2872–2875; (d) T. J. Donohoe and S. Butterworth, Oxidative cyclisation of diols derived from 1,5-dienes: formation of enantiopure cis-tetrahydrofurans by using catalytic osmium tetroxide; Formal synthesis of (+)-cis-solamin, Angew. Chem., Int. Ed., 2005, 44, 4766–4768Cr oxo-species: (e) E. J. Corey and D. C. Ha, Total synthesis of venustatriol, Tetrahedron Lett., 1988, 29, 3171–3174; (f) D. M. Walba and G. S. Stoudt, Oxidative cyclisation of 5,6-dihydroxyalkenes promoted by Cr(VI) oxo species: A novel cis-2,5-disubstituted tetrahydrofuran synthesis, Tetrahedron Lett., 1982, 23, 727–730; (g) B. D. Hammock, S. S. Gill and J. E. Casida, Synthesis and morphogenetic activity of derivatives and analogs of aryl geranyl ether juvenoids, J. Agric. Food Chem., 1974, 22, 379–385.
9. (a) J. E. Baldwin, M. J. Crossley and E.-M. M. Lehtonen, Stereospecificity of oxidative cycloaddition reactions of 1,5-dienes, J. Chem. Soc., Chem. Commun., 1979, 918–920; (b) E. Klein and W. Rojahn, Permanganate oxidation of 1,5-diene compounds, Tetrahedron, 1965, 21, 2353–2358; (c) A. Kötz and T. Steche, About the gradual oxidation of citronellol and geraniol, J. Prakt. Chem., 1924, 107, 193–210.
10. (a) T. J. Donohoe and S. Butterworth, A general oxidative cyclisation of 1,5-dienes using catalytic osmium tetroxide, Angew. Chem., Int. Ed., 2003, 42, 948–951; (b) T. J. Donohoe, J. J. G. Winter, M. Helliwell and G. Stemp, Hydrogen bonding control in the oxidative cyclisation of 1,5-dienes, Tetrahedron Lett., 2001, 42, 971–974; (c) M. de Champdore, M. Lasalvia and V. Piccialli, OsO₄-Catalysed oxidative cyclisation of geranyl and neryl acetate to cis-2,5-bis(hydroxymethyl)tetrahydrofurans, Tetrahedron Lett., 1998, 39, 9781–9784.
11. For cis and trans THF-diol mixture products from Ru-catalysed oxidative cyclisations of 1,5-dienes see: (a) V. Piccialli, T. Caserta, L. Caruso, L. Gomez-Paloma and G. Bifulco, RuO₄-mediated oxidative polycyclisation of linear polyenes, a new approach to the synthesis of the bis-THF diol core of antitumour cis-cis adjacent bis-THF annonaceous acetogenins, Tetrahedron, 2006, 62, 10989–11007; (b) S. Roth, S. Göhler, H. Cheng and C. B. W. Stark, A highly efficient procedure for ruthenium tetroxide catalysed oxidative cyclisations of 1,5-dienes, Eur. J. Org. Chem., 2005, 4109–4118; (c) S. Roth, S. Göhler, H. Cheng and C. B. W. Stark, A Highly Efficient Procedure for Ruthenium Tetroxide Catalysed Oxidative Cyclisations of 1,5-Dienes, Eur. J. Org. Chem., 2005, 4109–4118; (d) V. Piccialli and T. Caserta, Perruthenate ion. Another metal oxo species able to promote the oxidative cyclisation of 1,5-dienes to 2,5-disubstituted cis-tetrahydrofurans, Tetrahedron Lett., 2004, 45, 303–308; (e) V. Piccialli and N. Cavallo, Improved RuO₄-catalysed oxidative cyclisation of geraniol-type 1,5-dienes to cis-2,5-bis(hydroxymethyl)tetrahydrofuranyldiols, Tetrahedron Lett., 2001, 42, 4695–4699; (f) L. Albarella, D. Musumeci and D. Sica, Reactions of 1,5-dienes with ruthenium tetraoxide: stereoselective synthesis of tetrahydrofurandiols, Eur. J. Org. Chem., 2001, 997–1003; (g) P. H. J. Carlsen, T. Katsuki, V. S. Martin and K. B. Sharpless, A greatly improved procedure for ruthenium tetraoxide catalysed oxidations of organic compounds, J. Org. Chem., 1981, 46, 3936–3938.
12. Significantly, it was proposed that Mn(VI) or Mn(V) glycolate intermediate, and based on DFT calculations shown in ref. 13, enforces the 2,5-cis-relationship across the incipient THF ring during cyclisation step as indicated in Baldwin's proposed mechanism for the oxidative cyclisation of 1,5-dienes.
13. A. Poethig and T. Strassner, The mechanism of the permanganate-promoted oxidative cyclisation of 1,5-dienes - A DFT study, Collect. Czech. Chem. Commun., 2007, 72, 715–727.
14. For RuO₄ catalysed oxidative polycyclisation of isoprenoid polyenes for the synthesis of adjacently linked poly-THF rings see: (a) G. Bifulco, T. Caserta, L. Gomez-Paloma and V. Piccialli, RuO₄-promoted syn-oxidative polycyclisation of isoprenoid polyenes: a new stereoselective cascade process, Tetrahedron Lett., 2002, 43, 9265–9269; (b) G. Bifulco, T. Caserta, L. Gomez-Paloma and V. Piccialli, Corrigendum to “RuO₄-promoted syn-oxidative polycyclisation of isoprenoid polyenes: a new stereoselective cascade process”, Tetrahedron Lett., 2002, 43, 9265–9269 (Tetrahedron Lett., 2003, 44, 3429); (c) G. Bifulco, T. Caserta, L. Gomez-Paloma and V. Piccialli, RuO₄-promoted oxidative polycyclisation of isoprenoid polyenes. A further insight into the stereochemistry of the process, Tetrahedron Lett., 2003, 44, 5499–5503; (d) T. Caserta, V. Piccialli, L. Gomez-Paloma and G. Bifulco, RuO₄-catalysed oxidative polycyclisation of squalene. Determination of the configuration of the penta-tetrahydrofuranyl diol product, Tetrahedron, 2005, 61, 927–939; (e) V. Piccialli, N. Borbone and G. Oliviero, RuO₄-catalysed oxidative polycyclisation of the Cs-symmetric isoprenoid polyene digeranyl. An unexpected stereochemical outcome, Tetrahedron, 2008, 64, 11185–11192.
15. (a) A. A. Hussein, M. J. S. Phipps, C.-K. Skylaris and R. C. D. Brown, Mechanism of Os-Catalysed Oxidative Cyclisation of 1,5-Dienes, J. Org. Chem., 2019, 84, 15173–15183; (b) A. Poethig and T. Strassner, Stereoselective OsO₄-catalysed oxidative cyclisation of 1,5-dienes, J. Org. Chem., 2010, 75, 1967–1973; (c) P. J. di Dio, S. Zahn, C. B. W. Stark and B. Kirchner, Understanding Selectivities in Ligand-free Oxidative Cyclisations of 1,5-and 1,6-Dienes with RuO₄ from Density Functional Theory, Z. Naturforsch., B: J. Chem. Sci., 2010, 65, 367–375.
16. (a) J. Frunzke, C. Loschen and G. Frenking, Why Are Olefins Oxidized by RuO₄ under Cleavage of the Carbon-Carbon Bond whereas Oxidation by OsO₄ Yields cis-Diols?, J. Am. Chem. Soc., 2004, 126, 3642–3652; (b) T. Strassner and M. Drees, Rutheniumtetraoxide oxidation of alkenes - a density functional theory study, J. Mol. Struct.: THEOCHEM, 2004, 671, 197–204; (c) P. O. Norrby, H. C. Kolb and K. B. Sharpless, Calculations on the reaction of ruthenium tetroxide with olefins using density functional theory (DFT). Implications for the possibility of intermediates in osmium-catalysed asymmetric dihydroxylation, Organometallics, 1994, 13, 344–347.
17. For suitability of the DFT function M06 with Ru-containing system see: (a) S. Chen, Y. Zheng, T. Cui, E. Meggers and K. N. Houk, Arylketone π-Conjugation Controls Enantioselectivity in Asymmetric Alkynylations Catalysed by Centrochiral Ruthenium Complexes, J. Am. Chem. Soc., 2018, 140, 5146–5152; (b) J. S. Cannon, L. Zou, P. Liu, Y. Lan, D. J. O'Leary, K. N. Houk and R. H. Grubbs, Carboxylate-Assisted C(sp³)-H Activation in Olefin Metathesis-Relevant Ruthenium Complexes, J. Am. Chem. Soc., 2014, 136, 6733–6743; (c) Y.-F. Yang, L. W. Chung, X. Zhang, K. N. Houk and Y.-D. Wu, Ligand-Controlled Reactivity, Selectivity, and Mechanism of Cationic Ruthenium-Catalysed Hydrosilylations of Alkynes, Ketones, and Nitriles: A Theoretical Study, J. Org. Chem., 2014, 79, 8856–8864; (d) H. Miyazaki, M. B. Herbert, P. Liu, X. Dong, X. Xu, B. K. Keitz, T. Ung, G. Mkrtumyan, K. N. Houk and R. H. Grubbs, Z-Selective Ethenolysis with a Ruthenium Metathesis Catalyst: Experiment and Theory, J. Am. Chem. Soc., 2013, 135, 5848–5858.
18. Calculations on high spin multiplicity triplet and quintet were considered and shown in ESI.†.
19. (a) The ruthenate ester Ru(VI) was not isolated yet and there is no clear evidence of its formation although Sica and et al. had proposed the existence of Ru(VI) bisglycolate due to reoxidation Ru(VI) → Ru(VIII) glycolate after formation of Ru(VI) glycolate (see ref. 20); (b) Like osmylation reaction that gives osmate(VI) ester, the reaction of RuO₄ with double bond is called ruthenylation because it gives ruthenate(VI) ester.
20. (a) L. Albarella, F. Giordano, M. Lasalvia, V. Piccialli and D. Sica, Evidence for the existence of a cyclic ruthenium (VI) diester as an intermediate in the oxidative scission of (−)-α-pinene with RuO₄, Tetrahedron Lett., 1995, 36, 5267–5270; (b) V. Piccialli, D. Sica and D. Smaldone, Reaction of 7-dehydrocholesteryl acetate with RuO₄. First isolation of a cyclic ruthenium (VI) diester, Tetrahedron Lett., 1994, 35, 7093–7096.
21. (a) The low barrier and high exergonicity of reaction reflect the experimental reaction rate aspects which is comparingly more reactive than the other metal–oxo reagents MnO₄⁻ and OsO₄ (see ref. 13 and 15a, b), where the typical reaction time for Ru-catalysed oxidative cyclisation is 5–15 mins; (b) The barriers calculated for FRS and SRS by Dio et al., using a model of two alkenes rather than 1,5-diene, were high to be compared to the reaction time in addition to the fact their study were in accord with the general mechanistic proposal for the oxidative cyclisation of 1,5-dienes by RuO₄ (see ref. 15c).
22. It is very desirable to mention that Ru(VI) complex ([(Me₃tacn)-(CF₃CO₂)RuO₂]ClO₄) was isolated by Che et al. and used in cis-dihydroxylation of alkenes in which they also isolated the (3 + 2) cycloadduct intermediate Ru(IV) glycolate. (See ref. 23).
23. W.-P. Yip, W.-Y. Yu, N. Zhu and C.-M. Che, Alkene cis-Dihydroxylation by [(Me₃tacn)(CF₃CO₂)RuVIO₂]ClO₄ (Me₃tacn = 1,4,7-Trimethyl-1,4,7-triazacyclononane): Structural Characterization of (3 + 2) Cycloadducts and Kinetic Studies, J. Am. Chem. Soc., 2005, 127, 14239–14249.
24. The energy barrier for the inner sphere oxidation of R(VIII) glycolate 7_[ox] formation from 7_NaIO4 via TS 10 is 39.5 kcal mol⁻¹. If it is considered as an outer sphere pathway the barrier will be 33.2 kcal mol⁻¹. From both manners, formation of Ru(VIII) glycolate is disfavoured.
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26. (a) T. Ishizuka, H. Kotani and T. Kojima, Characteristics and reactivity of ruthenium-oxo complexes, Dalton Trans., 2016, 45, 16727–16750; (b) W. H. Leung and C. M. Che, High-valent ruthenium(IV) and -(VI) oxo complexes of octaethylporphyrin. Synthesis, spectroscopy, and reactivities, J. Am. Chem. Soc., 1989, 111, 8812–8818.
27. (a) B. Plietker, M. Niggemann and A. Pollrich, The acid accelerated ruthenium-catalysed dihydroxylation. Scope and limitations, Org. Biomol. Chem., 2004, 2, 1116–1124; (b) B. Plietker and M. Niggemann, The RuO₄-catalysed dihydroxylation, ketohydroxylation and mono oxidation-novel oxidation reactions for the synthesis of diols and [small alpha]-hydroxy ketones, Org. Biomol. Chem., 2004, 2, 2403–2407; (c) B. Plietker and M. Niggemann, An Improved Protocol for the RuO₄-Catalysed Dihydroxylation of Olefins, Org. Lett., 2003, 5, 3353–3356.
28. Any intermolecular (3 + 2) cycloaddition between Ru(VIII) 7_[ox] and another alkene (E-but-2-ene was used as a model to reduce the computational cost) to get Ru(VI) bisglycolate as called “second cycle” type was not found. However, in the Os-catalysed dihydroxylation of alkenes or oxidative cyclisation of 1,5-dienes, the second cycle pathways were noticed (see ref. 15a and 29).
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30. The Ru(VI) or Ru(VIII) glycolate have yet to be characterized or detected by any means due to the high instability. However, there is a week evidence on the existence of Ru(VI) bisglycolate. Sica et al. suggested the existence of Ru(VI) bisglycolate as an intermediate in the oxidative scission of (−)-α-pinene with RuO₄ performed in acetone–water (2 : 1) which gives α-ketol as the sole oxidation product (see ref. 20). Also, they proposed the same intermediate for reaction of 7-dehydrocholesteryl acetate with RuO₄ to give consequently 1,2-diol and α-ketol as final oxidation products. Their evidence was based on fast experiments monitored by NMR in which they compared their ¹H-NMR peaks with isolated Os(VI) bisglycolate.
31. For geometry of Ru(VI) complexes see: W. P. Griffith, The Chemistry of Ruthenium Oxidation Complexes, in Ruthenium Oxidation Complexes. Catalysis by Metal Complexes, Springer Netherlands, Dordrecht, 2011, vol. 34, pp. 1–134.
32. It was not possible to locate a TS for an intermolecular ruthenylation between 9_[ox][ox], like 7_[ox] glycolate, with E-but-2-ene whereas this is unlike to Os-catalysed oxidative cyclisation of 1,5-dienes.
33. In comparison to Ru(VI) glycolate 7, the Ru(VI) glycolate 7 did not undergo intermolecular ruthenylation and this is believed due to the geometrical difference, especially angle in O=Ru=O, between 7 and 9_[ox]. The angle of O=Ru=O in Ru(VI) diolate 9_[ox] is 119.4° and Ru(VI) glycolate 7 is 125.7°.
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Footnote

† Electronic supplementary information (ESI) available: Additional calculated reaction pathways, cartesian coordinates, absolute energies for reported structures. See DOI: 10.1039/d0ra02303e

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