[organic] ACS catalysis: olefin mediated selective ring closing metathesis of macrocyclic molecules

The author of this paper: orgchemist olefin metathesis is the rearrangement of carbon framework between two or three unsaturated carbon bonds catalyzed by metal olefin complex (metal carbene) The 2005 Nobel Prize in chemistry was awarded to Yves Chauvin, a French scientist, Robert H Grubbs, and Richard R Schrock for their outstanding contributions to olefin metathesis The problem of selectivity has always existed in various types of olefin metathesis There are problems of E / Z selectivity and olefin migration in intermolecular olefin metathesis; there are also a series of problems in intramolecular olefin metathesis (i.e ring closing metathesis, RCM), such as low yield and dimerization in ring closing compounds, and E / Z selectivity in ring closing compounds With the development of olefin metathesis, scientists began to study the selectivity problem of multiple olefins in the substrate Figure 1 Olefin metaphysis (source: ACS Catalyst.) Figure 2 Olefin cross metaphysis catalysts (source: ACS Catalyst.) recently, Liu Ruzhang's research group, School of chemistry and chemical engineering, Yangzhou University reported the selective study of cyclo metathesis of three highly active olefins in the substrate (ACS catalyst 2018, 8, 5574-5580）。 When RCM substrates (α, m, ω - three olefins) containing three highly active olefins react, α - olefins may react with ω - olefins to form α, ω - macrocyclic compounds, and α - olefins or ω - olefins may react with M - olefins to form α, M - or m, ω - mesocyclic compounds The biggest difference between the three olefins is that α - olefins and ω - olefins are monosubstituted olefins, while m-olefins are 1,3-disubstituted olefins The reactivity of the two olefins can be distinguished by controlling the reaction conditions When the author tried to synthesize nine membered ring compounds containing nitrogen, he found that under the catalysis of Hg2, a large number of eighteen membered ring compounds (EE as the main isomer) were obtained, but no nine membered ring compounds were obtained The yield of nine membered ring was 32% when G1 catalyst with low activity was used, and 60% when Ti (OiPr) 4 was used as additive When cat-z is used as catalyst, eighteen membered ring compounds (ZZ is the main isomer) can be obtained After the synthesis of two products with EE and ZZ as the main isomer, the author wants to get the product with EZ as the main isomer a Conditions: 1 (0.3–1 mmol), 5 mol % of catalyst, CH 2 Cl 2 (specified concentration), reflux, 18 h B yield of isolated product C determined by HPLC D Ti (o I PR) 4 (30 mol%) was added Table 1 Molecular and numerical selectivity in the RCM reaction of 1a (source: ACS Catalyst.) two substrates were prepared by olefin metathesis, HPLC separation and alkylation Then, when the cross coupling reaction of octadecyclic olefins was catalyzed by G1, Hg2 and cat-z, it was found that E-6 reacted with G1 and Hg2 to obtain the octadecyclic compounds with EE isomer as the main component In the e-rcm reaction of Z-6, a large number of z-alkenes are converted into e-alkenes, so that the proportion of EE and EZ isomers increases greatly The ratio difference (40:51:9 vs 80:18:2) reflects the different life of different catalysts Hg2 with higher activity has longer catalytic life than G1, which leads to more z-olefins to e-olefins and more catalytic cycles Scheme 1.syntheses of RCM predictors E-6 and Z-6, 18 h B yield of isolated product C determined by HPLC Table 2.selectivity in the macrocycle reactions of E-6 and z-6a (source: ACS Catalyst.) then, the author conducted a kinetic study to further understand the transformation of Z-E configuration in this macrocycle RCM reaction The starting rate is an important factor for the success of large ring RCM reaction, which is usually related to the lower substrate concentration (mm) and the higher catalyst dosage (up to 20 mol%) Lower substrate concentration can inhibit the self decomposition, while higher catalyst dosage can provide more active ruthenium to increase the contact opportunity between catalyst and substrate The kinetic experiments of the above substrates were carried out and the evidence of the transformation between ee-3, ez-3 and zz-3 was provided When the temperature is reduced, the secondary decomposition is inhibited, so the kinetic control of the e-rcm reaction of Z-6 is realized The kinetic experiments of cat-z catalyst show that the catalyst has kinetic control properties The results of kinetic experiments show that G1 catalyst needs to inhibit the transformation from Z to e at 0 ℃, so that the original z-olefin is not affected in the RCM reaction Figure 3 Kinetic studies (source: ACS Catalyst.) in the synthesis of eighteen membered ring, the author used the selected conditions to synthesize three isomeric compounds with high purity, and successfully realized the kinetic control In addition to the eighteen membered ring compounds, four different EE, EZ, Ze and ZZ isomers were obtained under the condition of asymmetric two side chains of the double bond Starting from cis and trans disubstituted olefins, the four isomers were synthesized by RCM reaction, and their selectivity was studied In addition, some α, M - or m, ω - mesocyclic compounds were synthesized Scheme 2 Syntheses of RCM precursors (source: ACS Catalyst.) experimental results show that the main RCM reaction of compounds above the seventeen membered ring is α, ω - macrocyclic compounds RCM reaction of compounds below the fifteen membered ring mainly produces middle ring compounds The RCM reactions of fifteen, sixteen and seventeen membered ring compounds have different characteristics With regard to the selectivity of ring size, the e-rcm reaction of e-isomers above the sixteen membered ring preferentially generates macrocycles, and the e-rcm reaction of E-10 or e-9 (sixteen or seventeen membered ring) yields z-olefins In the z-rcm reactions of e-isomers, the RCM reactions of compounds with more than 15 membered rings preferentially form large rings, and all of them have high z-selectivity In the e-rcm reaction of z-isomer, the high reactivity of z-olefin and G1 leads to the RCM reaction of the compounds below the seventeen membered ring to easily get the middle ring compounds Similarly, due to the energy problem, zz-15 is mainly formed in the e-rcm reaction of Z-9 In the z-rcm reaction of Z-isomers, the RCM reaction of compounds with more than 17 membered rings mainly produces macrocyclic products, and has good control ability of Z configuration Figure 4 Ringsize selectivity (source: ACS Catalyst.) conclusion: the author studied the ring size selectivity in E / z-rcm of E and Z isomers, and obtained four slightly different EE -, EZ -, Ze - and ZZ - isomers of macrocyclic diene For compounds with more than 17 rings, four types of reactions can provide good ring size selectivity For ring sizes of compounds below 15, the middle ring is the best product 15、 The RCM reactions of 16 and 17 ring compounds have different characteristics These studies will be of guiding significance for the synthesis of I-type macrocyclic olefins with two high activities.