Dalton Transactions
View Article Online View Journal
An international journal of inorganic chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Vidovic, M. Petkovic, F. Duzhin and A. Smarun, Dalton Trans., 2017, DOI: 10.1039/C7DT03041J. Volume 45 Number 1 7 January 2016 Pages 1–398
Dalton Transactions An international journal of inorganic chemistry www.rsc.org/dalton
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the author guidelines.
ISSN 1477-9226
PAPER Joseph T. Hupp, Omar K. Farha et al. Efficient extraction of sulfate from water using a Zr-metal–organic framework
Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the ethical guidelines, outlined in our author and reviewer resource centre, still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
rsc.li/dalton
Please do not adjust margins Dalton Transactions
Page 1 of 8
View Article Online
DOI: 10.1039/C7DT03041J
Dalton Transactions
Alkene-assisted cis-to-trans isomerization of non-conjugated polyunsaturated alkenes Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x www.rsc.org/
A. V. Smarun,a Fedor Duzhin,b M. Petkovićc and D. Vidović*a,d Complex [Cp*Ru(NCMe)3][PF6], 1a, has been identified as a cis-to-trans isomerization catalyst of various non-conjugated cispolyalkenes under exceptional kinetic control as no alkene conjugation was observed. According to the experimental and theoretical data, the cis-trans isomerization occurred via an alkene-assisted mechanism in which one cis-double bond always served as an anchoring site. Using a combination of multinuclear NMR spectroscopic evidence and mathematical methods it was possible to determine the extent of trans isomerization.
Introduction Cis-to-trans (or cis-trans) isomerization of alkenes is one of the most fundamentally important procedures in organic synthesis.1] This is because many preparative methods for the formation of carbon-carbon double bonds such as alkyne hydrogenation (Lindlar catalyst2 ), Wittig substitutions3 and alkene metathesis4 yield predominantly cis- or a mixture of cis/trans-alkenes. Radically,5 thermally6 and photochemically7 induced methods for alkene isomerization exist but, in general, these relatively harsh procedures suffer from double-bond migration and/or cross-coupling. Transition metal-mediated cistrans isomerization could potentially offer milder reaction conditions, better functional group tolerance and product selectivity. Unfortunately, target isomerization is also accompanied by double-bond migration unless the initial substrate’s double bond is movement-restricted by, for example, the presence of neighbouring aryl or tertiary-alkyl groups, or extended conjugated systems.8 In fact, most reports on transition metal-mediated cis-trans isomerization almost always use alkenes that contain movement-restricted double bonds presumably because the use of substrates that contain movement-unrestricted double bonds would lead to the establishment of a thermodynamic equilibrium between different positional isomers.8b,9 Furthermore, alkene metathesis could be used for cis-trans isomerization, but this method is also
affected by double-bond migration that could, to a certain degree, be suppressed for selected substrates by introducing various additives (e.g. benzoquinone).10 Few alkenes that contain movement-unrestricted double bonds (e.g. cis-4-octene and (Z)-5-phenyl-2-penten-1-ol) have been isomerized by a palladium-catalyst.1b However, these transformations are not only intolerant to alcohol and ester groups but also appear to produce positional isomers based on the amounts of unreacted substrates and the product yields. With respect to transition metal mediated isomerization of nonconjugated poly-alkenes, the most common outcome is the formation of conjugated systems or hydrogenation products.11,12 For example, selective Ru-, Pt- and Rh-based complexes were shown to reach up to 95% conversion of movement-unrestricted poly-alkenes into mixtures of conjugated products including signs of partial hydrogenation and polymerization.11 Herein, we report on selective cis-trans isomerization of polyunsaturated alkenes that contain movement-unrestricted double bonds (i.e. skipped polyalkenes) by a readily available Ru-based complex without the formation of any conjugated or hydrogenation side-products. The selectivity is believed to be achieved by an alkene–assisted mechanism,13 which introduces rigidity at the key mechanistic step eliminating the formation of the otherwise thermodynamically more stable conjugated products. Similar examples of olefin assistance giving rise to high regio- and/or stereoselectivity include allylic relay Suzki reactions, oxidative alkynylation of enallenes, isomerisation of N-allyl amides and regioselective 1,4-addition of organoboronic acid to dienones.14
a. Department
of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore. of Physical and Mathematical Sciences, Division of Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 63737 c. Faculty of Physical Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Republic of Serbia. d. Current address: School of Chemistry, Monash University, Melborune, Australia. Email: [email protected] Electronic Supplementary Information (ESI) available: General information concerning mathematical derivation of the formula for the extent of trans isomerization, additional tables, figures, schemes, characterization data and copies of multinuclear NMR spectra of attempted reactions are available. See DOI: 10.1039/x0xx00000x b. School
Results and discussion During our efforts to perform site-specific H/D exchange at the bis-allylic positions of polyunsaturated fatty acids (PUFAs),15 which all contain cis-double bonds, we discovered that a commercially available ruthenium complex, namely
J. Name., 2013, 00, 1-3 | 1
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
ARTICLE
Please do not adjust margins Dalton Transactions
Page 2 of 8 View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
Journal Name
Substrate 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 [a]POLY
E-Lin E-Lnn A-Lnn O-Lnn H-Lnn E-Ara E-DHA A-DHA O-DHA H-DHA E-Lin E-Lin-d4 T-Lnn POLY M-Ole
Catalyst loading, % 1 1 1 1 1 2 3 3 3 3 1 1 3 1[b] 5[c]
Time (h) 72 4 24 24 24 18 18 24 24 8 24 24 18 24 48
and M-Ole substrates do not contain bis-allylic positions. of positional isomers.
% of trans,trans at bis-allylic, a 5 0 1 4 0 25 34 31 31 35 1 2 0 n.a. n.a. [b]With
% of cis,trans at bis-allylic, b 76 79 49 81 78 67 58 47 65 59 54 28 73 n.a. n.a.
respect to the repeating unit.
[c]Reaction
% of trans at mono-allylic, c 43 77 48 83 78 75 73 58 78 79 28 16 73 80
% trans isomerization, t 43 52 32 57 52 63 65 55 66 67 28 16 49 80
37[d]
37[d]
was carried in acetone-d6 and was heated to 60 ˚C.
[d]Formation
[Cp*Ru(NCMe)3][PF6], 1a (Cp* = pentamethylcyclopentadienyl; Table 1), was quite efficient in selective cis-trans isomerization of various polyunsaturated alkenes. It was first realized that addition of ethyl linoleate (E-Lin) into a DCM-d2 solution containing 1% of complex 1a resulted in cis-trans isomerization of the double bonds with no evidence of alkene conjugation (entry 1, Table 1).16 This was quite significant considering that when the same reaction was repeated using either Grotjahn’s i bifunctional Ru-based catalyst, [CpRu( Pr2PIm)(NCMe)]PF6 or i [Cp*Ru( Pr2PIm)(NCMe)x]PF6 (Im = 4-tert-butyl-1methylimidazol-2-yl, x = 1 or 2),17 fast and exclusive formation of conjugated systems was observed.15,18 These results enticed us to investigate other similar polyunsaturated systems such as ethyl α-linolenate (E-Lnn, entry 2), ethyl arachidonate (E-Ara, entry 6) and ethyl docosahexaenoate (E-DHA, entry 7), triglyceride of linolenic acid (T-Lnn, entry 13) and several of their free acid (A-Lnn and A-DHA, entries 3 and 8, respectively), alcohol (O-Lnn and O-DHA entries 4 and 9, respectively) and hydrocarbon (H-Lnn and H-DHA entries 5 and 10, respectively) analogues. In all cases substantial cis-trans isomerization was observed with no indication of alkene conjugation or hydrogenation and, more importantly, the procedure was perfectly tolerant with respect to alcohol, carboxylic acid and
ester functional groups which was not always the case for other catalytic systems.1b 2( 1) + ( 1) + 2 =
(1)
2
The extent of trans isomerization (% of trans bonds, t, Table 1) was determined by the combination of experimental data and mathematical methods. First of all, each of the initially investigated substrates has two mono-allylic and one or more bis-allylic positions (Table 1), and the 1H and 13C NMR spectroscopic signals associated with these positions can be distinguished among various groups of geometric isomers.16 It was then possible to determine several important parameters such as: (i) the percentage of bis-allylic positions in reaction mixture that are surrounded by two trans-double bonds (parameter a), (ii) the percentage of bis-allylic positions in reaction mixture that are surrounded by one trans- and one cisdouble bonds (parameter b) and (iii) the percentage of the mono-allylic positions in reaction mixture that are next to a trans-bond (parameter c). These parameters allowed us to establish a mathematical equation 1 where m = number of
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Table 1. Cis-trans isomerization of non-conjugated polyunsaturated alkenes using complex 1a.
Please do not adjust margins Dalton Transactions
Page 3 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
double bonds,16 which can be used to calculate the extent of trans isomerization, t, for poly-alkene systems that contain skipped double bonds. According to the obtained t values (Table 1) three conclusions could be drawn: (i) free acid substrates A-Lnn and A-DHA were isomerized at slower reaction rates than their ester, alcohol or hydrocarbon analogues, (ii) as the number of the double bonds in the investigated substrates increased (going from E-Lin to EDHA) the extent of isomerization also increased (e.g. the t values for E-Lin and E-DHA are 43 and 65%, respectively) and (iii) even after extended periods of time trans isomerization for PUFA-like polyenes (entries 1-12) never reached the thermodynamic value of around 80%.5c,h The slow rate of isomerization for the free acid compounds was attributed to the dissociation ability (0.3 to 1%)19 of these species to form the corresponding carboxylates which would then compete with the alkene fragments for coordination to the ruthenium centre.20 The other two observations were attributed to the nature of the proposed mechanism (see below). As complex 1a does not contain a hydride ligand it was strongly believed that the π-allyl mechanism, also known as the η3-η1-η3 or π-σ-π mechanism, was involved in the observed cis-trans isomerization.21 The most important step in this mechanism appears to be the formation of an η3-allyl intermediate (Scheme 1) from the original coordination complex through oxidative addition of the allylic C-H bond. Apart from progressing further along the overall catalytic cycle (see Scheme 2) the allyl intermediate is also susceptible to reductive elimination and placement of the hydride atom at either end of the allyl ligand. Specifically, if the hydride atom attaches at the right side of the allyl system the original isomer is formed (Scheme 1). However, if the hydride atom attaches at the left end (i.e. 1,3-hydrogen shift) then a positional isomer is produced signifying the double bond movement. Thus, in order for a transition metal-mediated cis-trans isomerization to occur without the formation of positional isomer(s) the metal complex and/or the substrate need to restrict the movement of the hydridic H at the unwanted end of the allyl intermediate. We believe that the nature of investigated polyunsaturated substrates (containing two or more double bonds) allowed these substrates to block the undesirable hydride movement leading only to the formation of the geometric isomers. Scheme 1. A part of the overall allyl mechanism for alkene isomerization.
The proposed mechanism for the current cis-trans isomerization using a simple diene ligand is detailed in Scheme 2. Initially, the diene coordinates, by displacing the acetonitrile ligands, to the Ru centre using both of its double bonds (A). One of these η2-double bonds (in this case the one at the R end) serves as the anchoring site while the other one is isomerized.13
Scheme 2. Proposed mechanism for alkene-assisted cis-trans isomerization.
More specifically, the allylic C-H bond next to the isomerized double bond (at the R’ end) undergoes oxidative addition to ruthenium to form the first η3-allyl intermediate (B, Scheme 2). Next, the η3-allyl intermediate is converted to η1-intermediate C which allows for a rotation around C-C bond, at the site of the original C=C double bond, resulting in intermediate D. Formation of the second η3 -allyl intermediate (E), subsequent reductive elimination and return of the hydride to its original site (F) result in the observed cis-trans isomerization. Further evidence for the proposed mechanism was obtained from the computational studies on the model substrate (x=n=1, R=R'=Me, Table 1), that identified the allyl rotation (ts23, Scheme 3) as the rate determining step with the activation energy of around 30 kcal/mol. The barrier determined at the PCM-B2GP-PLYP/BS2//B3LYP/BS1 level16,22 appears to be overstated in comparison to the experimentally observed reaction rates. It is believed that water molecules do not play a significant role in the overall mechanism as in the case of our H/D experiments15 because the cis-trans reactions have been performed in dried DCM. It is then suspected that (in addition to the level of theory used in this case, which is not highly sophisticated) this disagreement results from neglecting solvent-solute interactions which are likely to affect the barrier height. Explicit solvent molecules were not considered, since they would substantially increase computational cost. Several conclusions could be drawn from a detailed examination of the proposed catalytic cycle and additional experimental observations that followed. The oxidative addition (formation of B or int2) most likely occurs by the H atom abstraction from the mono-allylic site (closer to R’) of the
J. Name., 2013, 00, 1-3 | 3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
Please do not adjust margins Dalton Transactions
Page 4 of 8 View Article Online
DOI: 10.1039/C7DT03041J
Journal Name
Scheme 3. Key intermediates and transition states for alkene-assisted cis-to-trans isomerisation of a cis,cis-diene substrate by [Cp(*)Ru]+ fragments (Cp(*) = Cp or Cp*) obtained at the PCM-B2GP-PLYP/BS2//B3LYP/BS1 level.16,22
diene as it is stereoelectronically more accessible than the H atoms at the bis-allylic site. In fact, according to the theoretical examinations a hydrogen transfer from the bis-allylic position is energetically very unfavourable16 even though more reactive H atoms are found at this site. More evidence for this hypothesis was gathered by using E-Lin enriched with deuterium (E-Lin-d4) at the mono-allylic positions (about 94%)15 resulting in considerable reduction of the isomerization rate (entries 11 and 12, Table 1). The kinetic isotope effect (kH/kD) was estimated to be around 1.7 which is consistent with the fact that this step is not rate limiting (Ea ~ 15 kcal/mol). Also, it is strongly believed that the restricted flexibility of intermediates B and E, due to the presence of the anchoring double bond, must completely prevent positional adjustment of the Ru-bound hydrogen in a way that the reductive elimination could only return the hydride atom at the original site of its abstraction yielding back intermediate A or forming intermediate F, respectively. Indeed, while the activation energy for the hydride going back to its original carbon site was calculated to be around 17 kcal/mol (E F), no low energy transition state could be identified for placing the same hydride at the other end of the allyl intermediate E. Therefore, the presence of the second alkene fragment was responsible for selective activation of allylic C-H bond in a course of oxidative addition as it controlled back
insertion preventing the formation of a conjugated system and/or positional isomer(s). Furthermore, the fact that cis-trans isomerization of these substrates was unable to reach the thermodynamic equilibrium (~ 80% of trans-bonds) could be explained by assuming that only a cis-double bond could serve as an anchoring site. This hypothesis is not only supported by the fact that cis-alkenes form decisively stronger bonding interactions with CpRu-like fragments than the corresponding trans-analogues,23 but also by additional evidence gathered from the examination of experimental data. Since cis-double bonds form strong anchoring interactions with ruthenium centre, isomerization rate of the last remaining cis-double bond in each substrate molecule (i.e. when every other cis-double bond has been isomerized to trans) must be dramatically lower than that of any other cis-double bond in the beginning of isomerization reaction. This would imply that at some point the progress of cis-trans isomerization of these substrates virtually stops and thus the formation of fully trans-products (such as trans,transE-Lin (EE-E-Lin), trans,trans,trans-E-Lnn (EEE-E-Lnn), etc) is prevented. Indeed, close examination of 1H and 13C NMR spectroscopic data16 for isomerization reactions of E-Lin and ELnn by 1a revealed that both of these reactions have reached their equilibrium points without or with nearly no formation of any bis-allylic positions surrounded by two trans-double bonds
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
ARTICLE
Please do not adjust margins Dalton Transactions
Page 5 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
(parameter a, entries 1-5, Table 1). In other words, there were no EE-E-Lin, ZEE-E-Lnn, EEZ-E-Lnn and EEE-E-Lnn geometric isomers formed in a course of these isomerization reactions, respectively. The fact that only two outer cis-double bonds of ELnn underwent cis-trans isomerization while its middle cisdouble bond remained intact strongly suggests that in PUFA-like poly-alkene systems internal cis-double bonds are better anchoring sites than two outer cis-double bonds. Furthermore, absence of fully trans-products such as EE-E-Lin and EEE-E-Lnn from the experimental equilibrium mixtures strongly suggests the inability of trans-double bonds to serve as the anchoring sites for alkene-assisted cis-trans isomerization. If it is, then, assumed that on average one cis-double bond must always serve as the anchoring site while all the other ones are allowed to reach thermodynamic equilibrium t value of 80% trans then the theoretical maximum extent of trans isomerization ( theor ) for E-Lin, E-Lnn/H-Lnn/O-Lnn/T-Lnn, EAra and E-DHA/H-DHA/O-DHA could be calculated using equation 2 yielding 40, 53, 60 and 66% trans, respectively.
values are in good agreement with the experimental t values of 43, 53 (avg.), 63 and 66 (avg.) %, respectively, for these substrates24 (Table 1). It can also be postulated that as the number of the double bonds in a molecule increases (parameter m in eq 2) theor will approach the thermodynamic value (eq 3). Indeed, using cis-polybutadiene (POLY) it was observed that about 80% of cis-bonds were converted to trans (entry 14, Table 1). This observation not only supported the initial hypothesis but also suggested that doubly skipped cis-alkenes could also be used for this type of cis-trans isomerization.
0.8( 1) ℎ =
ℎ = →∞
→∞
(2)
0.8( 1)
= 0.8 (3)
Further evidence for the necessity of the alkene assistance in the overall mechanism was obtained by investigating the isomerization of methyl oleate (M-Ole) using 1a (entry 15, Table 1). Not only a higher loading of 1a (5%) and harsher reaction conditions (60 °C) were required to observe cis-trans isomerization, but double bond movement (i.e. formation of a mixture of positional isomers) was also evident in the 13C NMR spectrum of the reaction mixture.16 Similarly, addition of complex 1a to trans,trans-isomer of E-Lin (EE-E-Lin) did not induce cis- trans isomerization under standard reaction conditions. However, under harsher reaction conditions, instead of producing a mixture of EZ-E-Lin and ZE-E-Lin isomers, as one would expect if EE-E-Lin was to follow an alkene-assisted mechanism, it resulted in extensive double bond conjugation, which is reminiscent of a "mono-alkene" behavior such as MOle. This finding further supports our hypothesis that transdouble bonds are incapable to serve as the anchoring sites for alkene-assisted cis-trans isomerization. Lastly, we examined the influence of the Cp ring methylation on the observed cis-trans isomerization. Figure 1 shows that methodical decrease in the Cp ring methylation (complexes 1b through 1h) systematically lowered the observed isomerization rates, in general. It is believed that poly-alkene substrates form significantly more stable bis-η2-alkene complexes with less sterically demanding CpRu+ fragment of complex 1h than with Cp*Ru+ fragment of 1a, and hence the rate of isomerization decreases. In other words, as methyl groups are sequentially added to the Cp ring, the strength of Ru-alkene bonding interactions appears to lessen allowing for the increase in the rate of the observed cis-trans isomerization. These Figure 1. The effect of the degree of steric demand around the ruthenium centre on the rate of E-Lnn isomerization by complexes 1 (1% mol) in DCM-d2 at room temperature. The lines serve as a visual tool to observe reaction progress.
Conclusions In summary, we reported on the first transition metal-mediated cis-to-trans isomerization of polyunsaturated alkenes containing movement-unrestricted double bonds. A readily available Ru-based complex was found to efficiently catalyse
J. Name., 2013, 00, 1-3 | 5
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
Please do not adjust margins Dalton Transactions
Page 6 of 8 View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
Journal Name We thank NTU (SUG M4080534) and the Ministry of Education, Science, and Technological Development of the Republic of Serbia within the framework of the project (MP, 172040) for the financial support. Computational analyses were performed on the PARADOX cluster at the Scientific Computing Laboratory of the Institute of Physics Belgrade, supported in part by the Ministry of Education, Science, and Technological Development of the Republic of Serbia under project No. ON171017 (MP).
Notes and references Experimental
1
Materials and methods All experiments were performed under dry nitrogen or argon atmosphere using standard Schlenk and/or drybox techniques. Unless specified otherwise, all commercially available reagents were used as received without further purification. DCM-d2 was degassed by means of saturation with inert gas and was stored over 4 Å molecular sieves. Complexes [Cp*Ru(NCCH3)3][PF6], 1,25 [CpRu(iPr2 PIm) i (NCCH3 )]PF6 and [Cp*Ru( Pr2PIm)(NCCH3 )x]PF6 (Im = 4-tertbutyl-1-methylimidazol-2-yl, x = 1 or 2)17 were prepared according to published preparatory methods. Alcohols O-Lnn and O-DHA and hydrocarbons H-Lnn and H-DHA were synthesized using an adaptation of the method for the synthesis of cis,cis-6,9-octadecadiene.26 Acids A-Lnn and A-DHA were synthesized using an adaptation of the method for the synthesis of linoleic acid.27 NMR spectra were recorded at 25 °C on Brüker Advance 500 (500 MHz listed below for 1 H = 499.9 MHz and 13 C{1 H} = 125.7 MHz). 1H and 13C NMR chemical shifts are reported in parts per million to low field relative to tetramethylsilane and referenced to residual solvent resonances (1 H NMR: 5.32 ppm and 13C NMR: 53.84 ppm for DCM-d2).
2 3 4 5
6 7
8
9 General procedure for isomerization of PUFAs and their respective hydrocarbon analogues. In a typical reaction of isomerization, J Young NMR tube was charged with 25-35 mg of substrate followed by 1.0 mL of DCM1 d2 after which first H NMR spectrum was acquired. Inside a glove box complex 1 was weighed in scintillation vial (1 mol% for E-Lin, E-Lnn, A-Lnn, O-Lnn and H-Lnn, 2 mol% for E-Ara and 3 mol% for E-DHA, A-DHA, O-DHA, H-DHA, T-Lnn). The substrate solution was then transferred into the vial. The mixture then was thoroughly mixed and transferred back into the NMR tube. Reaction progress was monitored by hourly 1 H NMR scans during first several hours followed by daily scans. Cis-trans isomerization of cis-polybutadiene was performed using an adaptation of the method for isomerization of PUFAs.
10
11
12 13 14
Conflicts of interest
15
There are no conflicts to declare.
16 17
Acknowledgements
(a) C. Dugave, L. Demange, Chem. Rev. 2003, 103, 2475. (b) I. S. Kim, G. R. Dong and Y. H. Jung, J. Org. Chem. 2007, 72, 5424. H. Lindlar, Helv. Chim. Acta 1952, 35, 446. G. Wittig, U. Schöllkopf, Chem. Ber. 1954, 87, 1318. R. H. Grubbs, Tetrahedron 2004, 60, 7117. See, for example: (a) R. H. Pallen, C. Sivertz, Can. J. Chem. 1957, 35, 723. (b) C. Walling, W. Helmreich, J. Am. Chem. Soc. 1959, 81, 1144. (c) C. Litchfield, J. E. Lord, A. F. Isbell and R. Reiser, J. Am. Oil Chem. Soc. 1963, 40, 553. (d) D. M. Golden, K. W. Egger and S. W. Benson, J. Am. Chem. Soc. 1964, 86, 5416. (e) A. J. Leusink, H. A. Budding and W. Drenth, J. Organomet. Chem. 1968, 11, 541. (f) D. E. McGreer, B. D. Page and D. P. Kaushal, Can. J. Chem. 1973, 51, 1239. (g) C. Chatgilialoglu, M. Ballestri, C. Ferreri and D. Vecchi, J. Org. Chem. 1995, 60, 3826. (h) C. Ferreri, C. Costantino, L. Perrotta, L. Landi, Q. G. Mulazzani and C. Chatgilialoglu, J. Am. Chem. Soc. 2001, 123, 4459. A. C. Cope, P. T. Moore and W. R. Moore, J. Am. Chem. Soc. 1960, 82, 1744. (a) J. J. Snyder, F. P. Tise, R. D. Davis and P. J. Kropp, J. Org. Chem. 1981, 46, 3609. (b) S. Prashanthi, P. Hemant Kumar, D. Siva, S. Rao Lanke, V. J. Rao, S. Basak and P. R. Bangal, J. Phys. Chem. C. 2011, 115, 20682. See for example: (a) J. Yu, M. J. Gaunt and J. B. Spencer, J. Org. Chem. 2002, 67, 4627. (b) S. Perdriau, M.-C. Chang, E. Otten, H. J. Heeres and J. G. de Vries, Chem. Eur. J. 2014, 20, 15434. A. V. Smarun, S. Wahyu, S. Pramono, S. Y. Koo, L. Y. Tan, R. Ganguly and D. Vidović, J. Organomet. Chem. 2017, 834, 1. (a) J. L. Bilhou, J. M. Basset, R. Mutin and W. F. Graydon, J. Am. Chem. Soc. 1977, 99, 4083. (b) S. H. Hong, D. P. Sanders, C. W. Lee and R. H. Grubbs, J. Am. Chem. Soc. 2005, 127, 17160. (a) P. Pertici, V. Ballantini, S. Catalano, A. Giuntoli, C. Malanga and G. Vitulli J. Mol. Catal. A: Chem. 1999, 144, 7. (b) R. C. Larock, X. Dong, S. Chung, C. K. Reddy and L. E. Ehlers, J. Am. Oil Chem. Soc. 2001, 78, 447. M. A. Grompone, P. Moyna, J. Am. Oil Chem. Soc. 1986, 63, 550. Y.-C. Hong, P. Gandeepan, S. Mannathan, W.-T. Lee and C.H. Cheng, Org. Lett. 2014, 16, 2806. (a) B. M. Trost, J. J. Cregg and N. Quach, J. Am. Chem. Soc. 2017, 139, 5133. (b) B. J. Stokes, A. J. Bischoff and M. S. Sigman, Chem. Sci. 2014, 5, 2336. (c) J. L. Henry, D. Posevins, B. Yang, Y. Qiu and J.-E. Bäckvall, Chem. Eur. J. 2017, 23, 7896. A. V. Smarun, M. Petković, M. S. Shchepinov and D. Vidović, Submitted See the supporting information. (a) G. Erdogan, D. B. Grotjahn, J. Am. Chem. Soc. 2009, 131, 10354. (b) G. Erdogan, D. B. Grotjahn, Top Catal. 2010, 53, 1055. (c) C. R. Larsen, G. Erdogan and D. B. Grotjahn, J. Am. Chem. Soc. 2014, 136, 1226.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
the cis-trans isomerization of poly-alkenes without the formation of positional isomers and/or conjugated systems. The absence of these thermodynamic products was attributed to the existence of an alkene-assisted mechanism in which one of the cis-double bonds served as the anchoring site. Apart from several molecules containing mono-skipped double bonds (i.e. PUFA-like molecules) this isomerization method was also demonstrated using a doubly-skipped system (e.g. cispolybutadiene).
Please do not adjust margins Dalton Transactions
Page 7 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
18 D. B. Grotjahn, US 8501032 B2, 2007 19 K. Quast, Adv. Powder Technol. 2016, 27, 207. 20 H. Werner, T. Braun, T. Daniel, O. Gevert and M. Schulz, J. Organomet. Chem. 1997, 54, 127. 21 E. Larionov, H. Li and C. Mazet, Chem. Commun. 2014, 50, 9816. 22 Computational details are provided in the supporting information: optimization was performed in the gas phase with a basis set BS1=3-21G(Cp/Cp*)-6-31G**(alkene)LANL2DZ(Ru), while single point energy calculations were performed in DCM introduced with the polarizable continuum model PCM, and a basis set BS2=6-311G**(C,H)-LANL2DZ(Ru). Also, intrinsic reaction coordinate calculations were performed for all transition states in order to confirm that they correspond to first order saddle points that connect the species of interest. Note that employment of the B2GP-PLYP functional reversed the order of stability of ts12 and int2. This is due to the fact that the potential energy surface on going from ts12 to int2 is shallow (see Figure S23). 23 K. M. McWilliams, A. Ellern and R. J. Angelici, Organometallics 2007, 26, 1665. 24 Acidic analogues were not averaged due to their slower isomerization rates. 25 A. Mercier, W. C. Yeo, J. Chou, P. D. Chaudhuri, G. Bernardinelli and E. P. Kündig, Chem. Commun. 2009, 5227. 26 Reduction of esters to alcohols: (a) A. E. Épshtein, V. E. Limanov and E. K. Skvortsova, Pharm. Chem. J. 1977, 11, 1238. Synthesis of esters of methanesulfonic acid: (b) M. Jayaraman, S. M. Ansell, B. L. Mui, Y. K. Tam, J. Chen, X. Du, D. Butler, L. Eltepu, S. Matsuda, J. K. Narayanannair, K. G. Rajeev, I. M. Hafez, A. Akinc, M. A. Maier, M. A. Tracy, P. R. Cullis, T. D. Madden, M. Manoharan and M. J. Hope, Angew. Chem. Int. Ed. 2012, 51, 8529. Synthesis of hydrocarbons: (c) W. J. Baumann, L. L. Jones, B. E. Barnum and H. K. Mangold, Chem. Phys. Lipids. 1966, 1, 63. 27 A. Y. Andreyev, H. S. Tsui, G. L. Milne, V. V. Shmanai, A. V. Bekish, M. A. Fomich, M. N. Pham, Y. Nong, A. N. Murphy, C. F. Clarke and M. S. Shchepinov, Free Radic. Biol. Med. 2015, 82, 63.
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
J. Name., 2013, 00, 1-3 | 7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Dalton Transactions View Article Online
Page 8 of 8
DOI: 10.1039/C7DT03041J
View Article Online View Journal
An international journal of inorganic chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Vidovic, M. Petkovic, F. Duzhin and A. Smarun, Dalton Trans., 2017, DOI: 10.1039/C7DT03041J. Volume 45 Number 1 7 January 2016 Pages 1–398
Dalton Transactions An international journal of inorganic chemistry www.rsc.org/dalton
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the author guidelines.
ISSN 1477-9226
PAPER Joseph T. Hupp, Omar K. Farha et al. Efficient extraction of sulfate from water using a Zr-metal–organic framework
Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the ethical guidelines, outlined in our author and reviewer resource centre, still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
rsc.li/dalton
Please do not adjust margins Dalton Transactions
Page 1 of 8
View Article Online
DOI: 10.1039/C7DT03041J
Dalton Transactions
Alkene-assisted cis-to-trans isomerization of non-conjugated polyunsaturated alkenes Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x www.rsc.org/
A. V. Smarun,a Fedor Duzhin,b M. Petkovićc and D. Vidović*a,d Complex [Cp*Ru(NCMe)3][PF6], 1a, has been identified as a cis-to-trans isomerization catalyst of various non-conjugated cispolyalkenes under exceptional kinetic control as no alkene conjugation was observed. According to the experimental and theoretical data, the cis-trans isomerization occurred via an alkene-assisted mechanism in which one cis-double bond always served as an anchoring site. Using a combination of multinuclear NMR spectroscopic evidence and mathematical methods it was possible to determine the extent of trans isomerization.
Introduction Cis-to-trans (or cis-trans) isomerization of alkenes is one of the most fundamentally important procedures in organic synthesis.1] This is because many preparative methods for the formation of carbon-carbon double bonds such as alkyne hydrogenation (Lindlar catalyst2 ), Wittig substitutions3 and alkene metathesis4 yield predominantly cis- or a mixture of cis/trans-alkenes. Radically,5 thermally6 and photochemically7 induced methods for alkene isomerization exist but, in general, these relatively harsh procedures suffer from double-bond migration and/or cross-coupling. Transition metal-mediated cistrans isomerization could potentially offer milder reaction conditions, better functional group tolerance and product selectivity. Unfortunately, target isomerization is also accompanied by double-bond migration unless the initial substrate’s double bond is movement-restricted by, for example, the presence of neighbouring aryl or tertiary-alkyl groups, or extended conjugated systems.8 In fact, most reports on transition metal-mediated cis-trans isomerization almost always use alkenes that contain movement-restricted double bonds presumably because the use of substrates that contain movement-unrestricted double bonds would lead to the establishment of a thermodynamic equilibrium between different positional isomers.8b,9 Furthermore, alkene metathesis could be used for cis-trans isomerization, but this method is also
affected by double-bond migration that could, to a certain degree, be suppressed for selected substrates by introducing various additives (e.g. benzoquinone).10 Few alkenes that contain movement-unrestricted double bonds (e.g. cis-4-octene and (Z)-5-phenyl-2-penten-1-ol) have been isomerized by a palladium-catalyst.1b However, these transformations are not only intolerant to alcohol and ester groups but also appear to produce positional isomers based on the amounts of unreacted substrates and the product yields. With respect to transition metal mediated isomerization of nonconjugated poly-alkenes, the most common outcome is the formation of conjugated systems or hydrogenation products.11,12 For example, selective Ru-, Pt- and Rh-based complexes were shown to reach up to 95% conversion of movement-unrestricted poly-alkenes into mixtures of conjugated products including signs of partial hydrogenation and polymerization.11 Herein, we report on selective cis-trans isomerization of polyunsaturated alkenes that contain movement-unrestricted double bonds (i.e. skipped polyalkenes) by a readily available Ru-based complex without the formation of any conjugated or hydrogenation side-products. The selectivity is believed to be achieved by an alkene–assisted mechanism,13 which introduces rigidity at the key mechanistic step eliminating the formation of the otherwise thermodynamically more stable conjugated products. Similar examples of olefin assistance giving rise to high regio- and/or stereoselectivity include allylic relay Suzki reactions, oxidative alkynylation of enallenes, isomerisation of N-allyl amides and regioselective 1,4-addition of organoboronic acid to dienones.14
a. Department
of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore. of Physical and Mathematical Sciences, Division of Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 63737 c. Faculty of Physical Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Republic of Serbia. d. Current address: School of Chemistry, Monash University, Melborune, Australia. Email: [email protected] Electronic Supplementary Information (ESI) available: General information concerning mathematical derivation of the formula for the extent of trans isomerization, additional tables, figures, schemes, characterization data and copies of multinuclear NMR spectra of attempted reactions are available. See DOI: 10.1039/x0xx00000x b. School
Results and discussion During our efforts to perform site-specific H/D exchange at the bis-allylic positions of polyunsaturated fatty acids (PUFAs),15 which all contain cis-double bonds, we discovered that a commercially available ruthenium complex, namely
J. Name., 2013, 00, 1-3 | 1
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
ARTICLE
Please do not adjust margins Dalton Transactions
Page 2 of 8 View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
Journal Name
Substrate 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 [a]POLY
E-Lin E-Lnn A-Lnn O-Lnn H-Lnn E-Ara E-DHA A-DHA O-DHA H-DHA E-Lin E-Lin-d4 T-Lnn POLY M-Ole
Catalyst loading, % 1 1 1 1 1 2 3 3 3 3 1 1 3 1[b] 5[c]
Time (h) 72 4 24 24 24 18 18 24 24 8 24 24 18 24 48
and M-Ole substrates do not contain bis-allylic positions. of positional isomers.
% of trans,trans at bis-allylic, a 5 0 1 4 0 25 34 31 31 35 1 2 0 n.a. n.a. [b]With
% of cis,trans at bis-allylic, b 76 79 49 81 78 67 58 47 65 59 54 28 73 n.a. n.a.
respect to the repeating unit.
[c]Reaction
% of trans at mono-allylic, c 43 77 48 83 78 75 73 58 78 79 28 16 73 80
% trans isomerization, t 43 52 32 57 52 63 65 55 66 67 28 16 49 80
37[d]
37[d]
was carried in acetone-d6 and was heated to 60 ˚C.
[d]Formation
[Cp*Ru(NCMe)3][PF6], 1a (Cp* = pentamethylcyclopentadienyl; Table 1), was quite efficient in selective cis-trans isomerization of various polyunsaturated alkenes. It was first realized that addition of ethyl linoleate (E-Lin) into a DCM-d2 solution containing 1% of complex 1a resulted in cis-trans isomerization of the double bonds with no evidence of alkene conjugation (entry 1, Table 1).16 This was quite significant considering that when the same reaction was repeated using either Grotjahn’s i bifunctional Ru-based catalyst, [CpRu( Pr2PIm)(NCMe)]PF6 or i [Cp*Ru( Pr2PIm)(NCMe)x]PF6 (Im = 4-tert-butyl-1methylimidazol-2-yl, x = 1 or 2),17 fast and exclusive formation of conjugated systems was observed.15,18 These results enticed us to investigate other similar polyunsaturated systems such as ethyl α-linolenate (E-Lnn, entry 2), ethyl arachidonate (E-Ara, entry 6) and ethyl docosahexaenoate (E-DHA, entry 7), triglyceride of linolenic acid (T-Lnn, entry 13) and several of their free acid (A-Lnn and A-DHA, entries 3 and 8, respectively), alcohol (O-Lnn and O-DHA entries 4 and 9, respectively) and hydrocarbon (H-Lnn and H-DHA entries 5 and 10, respectively) analogues. In all cases substantial cis-trans isomerization was observed with no indication of alkene conjugation or hydrogenation and, more importantly, the procedure was perfectly tolerant with respect to alcohol, carboxylic acid and
ester functional groups which was not always the case for other catalytic systems.1b 2( 1) + ( 1) + 2 =
(1)
2
The extent of trans isomerization (% of trans bonds, t, Table 1) was determined by the combination of experimental data and mathematical methods. First of all, each of the initially investigated substrates has two mono-allylic and one or more bis-allylic positions (Table 1), and the 1H and 13C NMR spectroscopic signals associated with these positions can be distinguished among various groups of geometric isomers.16 It was then possible to determine several important parameters such as: (i) the percentage of bis-allylic positions in reaction mixture that are surrounded by two trans-double bonds (parameter a), (ii) the percentage of bis-allylic positions in reaction mixture that are surrounded by one trans- and one cisdouble bonds (parameter b) and (iii) the percentage of the mono-allylic positions in reaction mixture that are next to a trans-bond (parameter c). These parameters allowed us to establish a mathematical equation 1 where m = number of
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Table 1. Cis-trans isomerization of non-conjugated polyunsaturated alkenes using complex 1a.
Please do not adjust margins Dalton Transactions
Page 3 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
double bonds,16 which can be used to calculate the extent of trans isomerization, t, for poly-alkene systems that contain skipped double bonds. According to the obtained t values (Table 1) three conclusions could be drawn: (i) free acid substrates A-Lnn and A-DHA were isomerized at slower reaction rates than their ester, alcohol or hydrocarbon analogues, (ii) as the number of the double bonds in the investigated substrates increased (going from E-Lin to EDHA) the extent of isomerization also increased (e.g. the t values for E-Lin and E-DHA are 43 and 65%, respectively) and (iii) even after extended periods of time trans isomerization for PUFA-like polyenes (entries 1-12) never reached the thermodynamic value of around 80%.5c,h The slow rate of isomerization for the free acid compounds was attributed to the dissociation ability (0.3 to 1%)19 of these species to form the corresponding carboxylates which would then compete with the alkene fragments for coordination to the ruthenium centre.20 The other two observations were attributed to the nature of the proposed mechanism (see below). As complex 1a does not contain a hydride ligand it was strongly believed that the π-allyl mechanism, also known as the η3-η1-η3 or π-σ-π mechanism, was involved in the observed cis-trans isomerization.21 The most important step in this mechanism appears to be the formation of an η3-allyl intermediate (Scheme 1) from the original coordination complex through oxidative addition of the allylic C-H bond. Apart from progressing further along the overall catalytic cycle (see Scheme 2) the allyl intermediate is also susceptible to reductive elimination and placement of the hydride atom at either end of the allyl ligand. Specifically, if the hydride atom attaches at the right side of the allyl system the original isomer is formed (Scheme 1). However, if the hydride atom attaches at the left end (i.e. 1,3-hydrogen shift) then a positional isomer is produced signifying the double bond movement. Thus, in order for a transition metal-mediated cis-trans isomerization to occur without the formation of positional isomer(s) the metal complex and/or the substrate need to restrict the movement of the hydridic H at the unwanted end of the allyl intermediate. We believe that the nature of investigated polyunsaturated substrates (containing two or more double bonds) allowed these substrates to block the undesirable hydride movement leading only to the formation of the geometric isomers. Scheme 1. A part of the overall allyl mechanism for alkene isomerization.
The proposed mechanism for the current cis-trans isomerization using a simple diene ligand is detailed in Scheme 2. Initially, the diene coordinates, by displacing the acetonitrile ligands, to the Ru centre using both of its double bonds (A). One of these η2-double bonds (in this case the one at the R end) serves as the anchoring site while the other one is isomerized.13
Scheme 2. Proposed mechanism for alkene-assisted cis-trans isomerization.
More specifically, the allylic C-H bond next to the isomerized double bond (at the R’ end) undergoes oxidative addition to ruthenium to form the first η3-allyl intermediate (B, Scheme 2). Next, the η3-allyl intermediate is converted to η1-intermediate C which allows for a rotation around C-C bond, at the site of the original C=C double bond, resulting in intermediate D. Formation of the second η3 -allyl intermediate (E), subsequent reductive elimination and return of the hydride to its original site (F) result in the observed cis-trans isomerization. Further evidence for the proposed mechanism was obtained from the computational studies on the model substrate (x=n=1, R=R'=Me, Table 1), that identified the allyl rotation (ts23, Scheme 3) as the rate determining step with the activation energy of around 30 kcal/mol. The barrier determined at the PCM-B2GP-PLYP/BS2//B3LYP/BS1 level16,22 appears to be overstated in comparison to the experimentally observed reaction rates. It is believed that water molecules do not play a significant role in the overall mechanism as in the case of our H/D experiments15 because the cis-trans reactions have been performed in dried DCM. It is then suspected that (in addition to the level of theory used in this case, which is not highly sophisticated) this disagreement results from neglecting solvent-solute interactions which are likely to affect the barrier height. Explicit solvent molecules were not considered, since they would substantially increase computational cost. Several conclusions could be drawn from a detailed examination of the proposed catalytic cycle and additional experimental observations that followed. The oxidative addition (formation of B or int2) most likely occurs by the H atom abstraction from the mono-allylic site (closer to R’) of the
J. Name., 2013, 00, 1-3 | 3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
Please do not adjust margins Dalton Transactions
Page 4 of 8 View Article Online
DOI: 10.1039/C7DT03041J
Journal Name
Scheme 3. Key intermediates and transition states for alkene-assisted cis-to-trans isomerisation of a cis,cis-diene substrate by [Cp(*)Ru]+ fragments (Cp(*) = Cp or Cp*) obtained at the PCM-B2GP-PLYP/BS2//B3LYP/BS1 level.16,22
diene as it is stereoelectronically more accessible than the H atoms at the bis-allylic site. In fact, according to the theoretical examinations a hydrogen transfer from the bis-allylic position is energetically very unfavourable16 even though more reactive H atoms are found at this site. More evidence for this hypothesis was gathered by using E-Lin enriched with deuterium (E-Lin-d4) at the mono-allylic positions (about 94%)15 resulting in considerable reduction of the isomerization rate (entries 11 and 12, Table 1). The kinetic isotope effect (kH/kD) was estimated to be around 1.7 which is consistent with the fact that this step is not rate limiting (Ea ~ 15 kcal/mol). Also, it is strongly believed that the restricted flexibility of intermediates B and E, due to the presence of the anchoring double bond, must completely prevent positional adjustment of the Ru-bound hydrogen in a way that the reductive elimination could only return the hydride atom at the original site of its abstraction yielding back intermediate A or forming intermediate F, respectively. Indeed, while the activation energy for the hydride going back to its original carbon site was calculated to be around 17 kcal/mol (E F), no low energy transition state could be identified for placing the same hydride at the other end of the allyl intermediate E. Therefore, the presence of the second alkene fragment was responsible for selective activation of allylic C-H bond in a course of oxidative addition as it controlled back
insertion preventing the formation of a conjugated system and/or positional isomer(s). Furthermore, the fact that cis-trans isomerization of these substrates was unable to reach the thermodynamic equilibrium (~ 80% of trans-bonds) could be explained by assuming that only a cis-double bond could serve as an anchoring site. This hypothesis is not only supported by the fact that cis-alkenes form decisively stronger bonding interactions with CpRu-like fragments than the corresponding trans-analogues,23 but also by additional evidence gathered from the examination of experimental data. Since cis-double bonds form strong anchoring interactions with ruthenium centre, isomerization rate of the last remaining cis-double bond in each substrate molecule (i.e. when every other cis-double bond has been isomerized to trans) must be dramatically lower than that of any other cis-double bond in the beginning of isomerization reaction. This would imply that at some point the progress of cis-trans isomerization of these substrates virtually stops and thus the formation of fully trans-products (such as trans,transE-Lin (EE-E-Lin), trans,trans,trans-E-Lnn (EEE-E-Lnn), etc) is prevented. Indeed, close examination of 1H and 13C NMR spectroscopic data16 for isomerization reactions of E-Lin and ELnn by 1a revealed that both of these reactions have reached their equilibrium points without or with nearly no formation of any bis-allylic positions surrounded by two trans-double bonds
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
ARTICLE
Please do not adjust margins Dalton Transactions
Page 5 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
(parameter a, entries 1-5, Table 1). In other words, there were no EE-E-Lin, ZEE-E-Lnn, EEZ-E-Lnn and EEE-E-Lnn geometric isomers formed in a course of these isomerization reactions, respectively. The fact that only two outer cis-double bonds of ELnn underwent cis-trans isomerization while its middle cisdouble bond remained intact strongly suggests that in PUFA-like poly-alkene systems internal cis-double bonds are better anchoring sites than two outer cis-double bonds. Furthermore, absence of fully trans-products such as EE-E-Lin and EEE-E-Lnn from the experimental equilibrium mixtures strongly suggests the inability of trans-double bonds to serve as the anchoring sites for alkene-assisted cis-trans isomerization. If it is, then, assumed that on average one cis-double bond must always serve as the anchoring site while all the other ones are allowed to reach thermodynamic equilibrium t value of 80% trans then the theoretical maximum extent of trans isomerization ( theor ) for E-Lin, E-Lnn/H-Lnn/O-Lnn/T-Lnn, EAra and E-DHA/H-DHA/O-DHA could be calculated using equation 2 yielding 40, 53, 60 and 66% trans, respectively.
values are in good agreement with the experimental t values of 43, 53 (avg.), 63 and 66 (avg.) %, respectively, for these substrates24 (Table 1). It can also be postulated that as the number of the double bonds in a molecule increases (parameter m in eq 2) theor will approach the thermodynamic value (eq 3). Indeed, using cis-polybutadiene (POLY) it was observed that about 80% of cis-bonds were converted to trans (entry 14, Table 1). This observation not only supported the initial hypothesis but also suggested that doubly skipped cis-alkenes could also be used for this type of cis-trans isomerization.
0.8( 1) ℎ =
ℎ = →∞
→∞
(2)
0.8( 1)
= 0.8 (3)
Further evidence for the necessity of the alkene assistance in the overall mechanism was obtained by investigating the isomerization of methyl oleate (M-Ole) using 1a (entry 15, Table 1). Not only a higher loading of 1a (5%) and harsher reaction conditions (60 °C) were required to observe cis-trans isomerization, but double bond movement (i.e. formation of a mixture of positional isomers) was also evident in the 13C NMR spectrum of the reaction mixture.16 Similarly, addition of complex 1a to trans,trans-isomer of E-Lin (EE-E-Lin) did not induce cis- trans isomerization under standard reaction conditions. However, under harsher reaction conditions, instead of producing a mixture of EZ-E-Lin and ZE-E-Lin isomers, as one would expect if EE-E-Lin was to follow an alkene-assisted mechanism, it resulted in extensive double bond conjugation, which is reminiscent of a "mono-alkene" behavior such as MOle. This finding further supports our hypothesis that transdouble bonds are incapable to serve as the anchoring sites for alkene-assisted cis-trans isomerization. Lastly, we examined the influence of the Cp ring methylation on the observed cis-trans isomerization. Figure 1 shows that methodical decrease in the Cp ring methylation (complexes 1b through 1h) systematically lowered the observed isomerization rates, in general. It is believed that poly-alkene substrates form significantly more stable bis-η2-alkene complexes with less sterically demanding CpRu+ fragment of complex 1h than with Cp*Ru+ fragment of 1a, and hence the rate of isomerization decreases. In other words, as methyl groups are sequentially added to the Cp ring, the strength of Ru-alkene bonding interactions appears to lessen allowing for the increase in the rate of the observed cis-trans isomerization. These Figure 1. The effect of the degree of steric demand around the ruthenium centre on the rate of E-Lnn isomerization by complexes 1 (1% mol) in DCM-d2 at room temperature. The lines serve as a visual tool to observe reaction progress.
Conclusions In summary, we reported on the first transition metal-mediated cis-to-trans isomerization of polyunsaturated alkenes containing movement-unrestricted double bonds. A readily available Ru-based complex was found to efficiently catalyse
J. Name., 2013, 00, 1-3 | 5
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
Please do not adjust margins Dalton Transactions
Page 6 of 8 View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
Journal Name We thank NTU (SUG M4080534) and the Ministry of Education, Science, and Technological Development of the Republic of Serbia within the framework of the project (MP, 172040) for the financial support. Computational analyses were performed on the PARADOX cluster at the Scientific Computing Laboratory of the Institute of Physics Belgrade, supported in part by the Ministry of Education, Science, and Technological Development of the Republic of Serbia under project No. ON171017 (MP).
Notes and references Experimental
1
Materials and methods All experiments were performed under dry nitrogen or argon atmosphere using standard Schlenk and/or drybox techniques. Unless specified otherwise, all commercially available reagents were used as received without further purification. DCM-d2 was degassed by means of saturation with inert gas and was stored over 4 Å molecular sieves. Complexes [Cp*Ru(NCCH3)3][PF6], 1,25 [CpRu(iPr2 PIm) i (NCCH3 )]PF6 and [Cp*Ru( Pr2PIm)(NCCH3 )x]PF6 (Im = 4-tertbutyl-1-methylimidazol-2-yl, x = 1 or 2)17 were prepared according to published preparatory methods. Alcohols O-Lnn and O-DHA and hydrocarbons H-Lnn and H-DHA were synthesized using an adaptation of the method for the synthesis of cis,cis-6,9-octadecadiene.26 Acids A-Lnn and A-DHA were synthesized using an adaptation of the method for the synthesis of linoleic acid.27 NMR spectra were recorded at 25 °C on Brüker Advance 500 (500 MHz listed below for 1 H = 499.9 MHz and 13 C{1 H} = 125.7 MHz). 1H and 13C NMR chemical shifts are reported in parts per million to low field relative to tetramethylsilane and referenced to residual solvent resonances (1 H NMR: 5.32 ppm and 13C NMR: 53.84 ppm for DCM-d2).
2 3 4 5
6 7
8
9 General procedure for isomerization of PUFAs and their respective hydrocarbon analogues. In a typical reaction of isomerization, J Young NMR tube was charged with 25-35 mg of substrate followed by 1.0 mL of DCM1 d2 after which first H NMR spectrum was acquired. Inside a glove box complex 1 was weighed in scintillation vial (1 mol% for E-Lin, E-Lnn, A-Lnn, O-Lnn and H-Lnn, 2 mol% for E-Ara and 3 mol% for E-DHA, A-DHA, O-DHA, H-DHA, T-Lnn). The substrate solution was then transferred into the vial. The mixture then was thoroughly mixed and transferred back into the NMR tube. Reaction progress was monitored by hourly 1 H NMR scans during first several hours followed by daily scans. Cis-trans isomerization of cis-polybutadiene was performed using an adaptation of the method for isomerization of PUFAs.
10
11
12 13 14
Conflicts of interest
15
There are no conflicts to declare.
16 17
Acknowledgements
(a) C. Dugave, L. Demange, Chem. Rev. 2003, 103, 2475. (b) I. S. Kim, G. R. Dong and Y. H. Jung, J. Org. Chem. 2007, 72, 5424. H. Lindlar, Helv. Chim. Acta 1952, 35, 446. G. Wittig, U. Schöllkopf, Chem. Ber. 1954, 87, 1318. R. H. Grubbs, Tetrahedron 2004, 60, 7117. See, for example: (a) R. H. Pallen, C. Sivertz, Can. J. Chem. 1957, 35, 723. (b) C. Walling, W. Helmreich, J. Am. Chem. Soc. 1959, 81, 1144. (c) C. Litchfield, J. E. Lord, A. F. Isbell and R. Reiser, J. Am. Oil Chem. Soc. 1963, 40, 553. (d) D. M. Golden, K. W. Egger and S. W. Benson, J. Am. Chem. Soc. 1964, 86, 5416. (e) A. J. Leusink, H. A. Budding and W. Drenth, J. Organomet. Chem. 1968, 11, 541. (f) D. E. McGreer, B. D. Page and D. P. Kaushal, Can. J. Chem. 1973, 51, 1239. (g) C. Chatgilialoglu, M. Ballestri, C. Ferreri and D. Vecchi, J. Org. Chem. 1995, 60, 3826. (h) C. Ferreri, C. Costantino, L. Perrotta, L. Landi, Q. G. Mulazzani and C. Chatgilialoglu, J. Am. Chem. Soc. 2001, 123, 4459. A. C. Cope, P. T. Moore and W. R. Moore, J. Am. Chem. Soc. 1960, 82, 1744. (a) J. J. Snyder, F. P. Tise, R. D. Davis and P. J. Kropp, J. Org. Chem. 1981, 46, 3609. (b) S. Prashanthi, P. Hemant Kumar, D. Siva, S. Rao Lanke, V. J. Rao, S. Basak and P. R. Bangal, J. Phys. Chem. C. 2011, 115, 20682. See for example: (a) J. Yu, M. J. Gaunt and J. B. Spencer, J. Org. Chem. 2002, 67, 4627. (b) S. Perdriau, M.-C. Chang, E. Otten, H. J. Heeres and J. G. de Vries, Chem. Eur. J. 2014, 20, 15434. A. V. Smarun, S. Wahyu, S. Pramono, S. Y. Koo, L. Y. Tan, R. Ganguly and D. Vidović, J. Organomet. Chem. 2017, 834, 1. (a) J. L. Bilhou, J. M. Basset, R. Mutin and W. F. Graydon, J. Am. Chem. Soc. 1977, 99, 4083. (b) S. H. Hong, D. P. Sanders, C. W. Lee and R. H. Grubbs, J. Am. Chem. Soc. 2005, 127, 17160. (a) P. Pertici, V. Ballantini, S. Catalano, A. Giuntoli, C. Malanga and G. Vitulli J. Mol. Catal. A: Chem. 1999, 144, 7. (b) R. C. Larock, X. Dong, S. Chung, C. K. Reddy and L. E. Ehlers, J. Am. Oil Chem. Soc. 2001, 78, 447. M. A. Grompone, P. Moyna, J. Am. Oil Chem. Soc. 1986, 63, 550. Y.-C. Hong, P. Gandeepan, S. Mannathan, W.-T. Lee and C.H. Cheng, Org. Lett. 2014, 16, 2806. (a) B. M. Trost, J. J. Cregg and N. Quach, J. Am. Chem. Soc. 2017, 139, 5133. (b) B. J. Stokes, A. J. Bischoff and M. S. Sigman, Chem. Sci. 2014, 5, 2336. (c) J. L. Henry, D. Posevins, B. Yang, Y. Qiu and J.-E. Bäckvall, Chem. Eur. J. 2017, 23, 7896. A. V. Smarun, M. Petković, M. S. Shchepinov and D. Vidović, Submitted See the supporting information. (a) G. Erdogan, D. B. Grotjahn, J. Am. Chem. Soc. 2009, 131, 10354. (b) G. Erdogan, D. B. Grotjahn, Top Catal. 2010, 53, 1055. (c) C. R. Larsen, G. Erdogan and D. B. Grotjahn, J. Am. Chem. Soc. 2014, 136, 1226.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
the cis-trans isomerization of poly-alkenes without the formation of positional isomers and/or conjugated systems. The absence of these thermodynamic products was attributed to the existence of an alkene-assisted mechanism in which one of the cis-double bonds served as the anchoring site. Apart from several molecules containing mono-skipped double bonds (i.e. PUFA-like molecules) this isomerization method was also demonstrated using a doubly-skipped system (e.g. cispolybutadiene).
Please do not adjust margins Dalton Transactions
Page 7 of 8
View Article Online
DOI: 10.1039/C7DT03041J
ARTICLE
18 D. B. Grotjahn, US 8501032 B2, 2007 19 K. Quast, Adv. Powder Technol. 2016, 27, 207. 20 H. Werner, T. Braun, T. Daniel, O. Gevert and M. Schulz, J. Organomet. Chem. 1997, 54, 127. 21 E. Larionov, H. Li and C. Mazet, Chem. Commun. 2014, 50, 9816. 22 Computational details are provided in the supporting information: optimization was performed in the gas phase with a basis set BS1=3-21G(Cp/Cp*)-6-31G**(alkene)LANL2DZ(Ru), while single point energy calculations were performed in DCM introduced with the polarizable continuum model PCM, and a basis set BS2=6-311G**(C,H)-LANL2DZ(Ru). Also, intrinsic reaction coordinate calculations were performed for all transition states in order to confirm that they correspond to first order saddle points that connect the species of interest. Note that employment of the B2GP-PLYP functional reversed the order of stability of ts12 and int2. This is due to the fact that the potential energy surface on going from ts12 to int2 is shallow (see Figure S23). 23 K. M. McWilliams, A. Ellern and R. J. Angelici, Organometallics 2007, 26, 1665. 24 Acidic analogues were not averaged due to their slower isomerization rates. 25 A. Mercier, W. C. Yeo, J. Chou, P. D. Chaudhuri, G. Bernardinelli and E. P. Kündig, Chem. Commun. 2009, 5227. 26 Reduction of esters to alcohols: (a) A. E. Épshtein, V. E. Limanov and E. K. Skvortsova, Pharm. Chem. J. 1977, 11, 1238. Synthesis of esters of methanesulfonic acid: (b) M. Jayaraman, S. M. Ansell, B. L. Mui, Y. K. Tam, J. Chen, X. Du, D. Butler, L. Eltepu, S. Matsuda, J. K. Narayanannair, K. G. Rajeev, I. M. Hafez, A. Akinc, M. A. Maier, M. A. Tracy, P. R. Cullis, T. D. Madden, M. Manoharan and M. J. Hope, Angew. Chem. Int. Ed. 2012, 51, 8529. Synthesis of hydrocarbons: (c) W. J. Baumann, L. L. Jones, B. E. Barnum and H. K. Mangold, Chem. Phys. Lipids. 1966, 1, 63. 27 A. Y. Andreyev, H. S. Tsui, G. L. Milne, V. V. Shmanai, A. V. Bekish, M. A. Fomich, M. N. Pham, Y. Nong, A. N. Murphy, C. F. Clarke and M. S. Shchepinov, Free Radic. Biol. Med. 2015, 82, 63.
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Journal Name
J. Name., 2013, 00, 1-3 | 7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Dalton Transactions Accepted Manuscript
Published on 03 October 2017. Downloaded by University of Newcastle on 06/10/2017 19:01:42.
Dalton Transactions View Article Online
Page 8 of 8
DOI: 10.1039/C7DT03041J
