Ruthenium-catalyzed formal sp3 C–H activation of allylsilanes/esters with olefins: efficient access to functionalized 1,3-dienes |
| |
Authors: | Dattatraya H Dethe Nagabhushana C Beeralingappa Saikat Das Appasaheb K Nirpal |
| |
Institution: | Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016 India, |
| |
Abstract: | Ru-catalysed oxidative coupling of allylsilanes and allyl esters with activated olefins has been developed via isomerization followed by C(allyl)–H activation providing efficient access to stereodefined 1,3-dienes in excellent yields. Mild reaction conditions, less expensive catalysts, and excellent regio- and diastereoselectivity ensure universality of the reaction. In addition, the unique power of this reaction was illustrated by performing the Diels–Alder reaction, and enantioselective synthesis of highly functionalized cyclohexenone and piperidine and finally synthetic utility was further demonstrated by the efficient synthesis of norpyrenophorin, an antifungal agent.Ru-catalysed oxidative coupling of allylsilanes and allyl esters with activated olefins has been developed via isomerization followed by C(allyl)–H activation providing efficient access to stereodefined 1,3-dienes in excellent yields.1,3-Dienes not only are widespread structural motifs in biologically pertinent molecules but also feature as a foundation for a broad range of chemical transformations.1–14 Indeed, these conjugated dienes serve as substrates in many fundamental synthetic methodologies such as cycloaddition, metathesis, ene reactions, oxidoreduction, or reductive aldolization. It is well-understood that the geometry of olefins often influences the stereochemical outcome and the reactivity of reactions involving 1,3-dienes.15 Hence, a plethora of synthetic methods have been developed for the stereoselective construction of substituted 1,3-dienes.16–24 The past decade has witnessed a huge advancement in the field of metal-catalyzed C–H activation/functionalization.25–27 Although, a significant amount of work in the field of C(alkyl)–H and C(aryl)–H activation has been reported; C(alkenyl)–H activation has not been explored conspicuously, probably due to the complications caused by competitive reactivity of the alkene moiety, which can make chemoselectivity a significant challenge. Over the past few years, several different palladium-based protocols have been developed for C(alkenyl)–H functionalization, but the reactions are generally limited to employing conjugated alkenes, such as styrenes,28–31 acrylates/acrylamides,32–36 enamides,37 and enol esters/ethers.38,39 To date, only a few reports have appeared in the literature for expanding this reactivity towards non-conjugated olefins, which can be exemplified by camphene dimerization,40 and carboxylate-directed C(alkenyl)–H alkenylation of 1,4-cyclohexadienes.41 In 2009, Trost et al. reported a ruthenium-catalyzed stereoselective alkene–alkyne coupling method for the synthesis of 1,3-dienes.42 The same group also reported alkene–alkyne coupling for the stereoselective synthesis of trisubstituted ene carbamates.43 A palladium catalyzed chelation control method for the synthesis of dienes via alkenyl sp2 C–H bond functionalization was described by Loh et al.44 Recently, Engle and coworkers reported an elegant approach for synthesis of highly substituted 1,3-dienes from two different alkenes using an 8-aminoquinoline directed, palladium(ii)-mediated C(alkenyl)–H activation strategy.45 Allyl and vinyl silanes are known as indispensable nucleophiles in synthetic chemistry.46 Alder ene reactions of allyl silanes with alkynes are reported for the synthesis of 1,4-dienes.47 Innumerable methods are known for the preparation of both allyl and vinyl silanes48–52 but limitations are associated with many of the current protocols, which impedes the synthesis of unsaturated organosilanes in an efficient manner. Silicon-functionalized building blocks are used as coupling partners in the Hiyama reaction53 and are easily converted into iodo-functionalized derivatives (precursor for the Suzuki cross-coupling reaction), but there is little attention given for the synthesis of functionalized vinyl silanes. Herein, we report a general approach for the stereoselective synthesis of trisubstituted 1,3-dienes by the Ru-catalyzed C(sp3)–H functionalization reaction of allylsilanes (Scheme 1).Open in a separate windowHighly stereoselective construction of 1,3-dienes.In 1993, Trost and coworkers reported an elegant method for highly chemoselective ruthenium-catalyzed redox isomerization of allyl alcohols without affecting the primary and secondary alcohols and isolated double bonds.54,55 Inspired by the potential of ruthenium for such isomerization of double bonds in allyl alcohols, we sought to identify a ruthenium-based catalytic system that can promote isomerization of olefins in allylsilanes followed by in situ oxidative coupling with an activated olefin to form substituted 1,3-dienes. We initiated our studies by choosing trimethylallylsilane 1a and acrylate 2a by using a commercially available RuCl2(p-cymene)]2 catalyst in the presence of AgSbF6 as an additive and co-oxidant Cu(OAc)2 in 1,2-DCE at 100 °C. Interestingly, it resulted into direct formation of (2E,4Z)-1,3-diene 3aa as a single isomer in 55% yield. It is likely that this reaction occurs by C(allyl)–H activation of the π-allyl ruthenium complex followed by oxidative coupling with the acrylate and leaving the silyl group intact ( Next, the regioselective C–H insertion of vinyl silanes could be controlled by stabilization of the carbon–metal (C–M) bond in the α-position to silicon. This stability arises due to the overlapping of the filled carbon–metal orbital with the d orbitals on silicon or the antibonding orbitals of the methyl–silicon (Me–Si) bond.57 The stereochemistry of the diene was established by 1D and 2D spectroscopic analysis of the compound 3aa. To quantify the C–H activation mediated coupling efficiency, an extensive optimization study was conducted (allylsilanes followed by in situ oxidative coupling with an activated olefin to form substituted 1,3-dienes). The change of solvents from 1,2-DCE to t-AmOH, DMF, dioxane, THF or MeCN did not give any satisfactory result, rather a very sluggish reaction rate or decomposition of starting materials was observed in each case (entry 2–6).Optimization of reaction conditionsa |
---|
Entry | Additive (20 mol%) | Oxidant (2 equiv.) | Solvent | Yieldb (%) |
---|
1 | AgSbF6 | Cu(OAc)2 | DCE | 55 | 2 | AgSbF6 | Cu(OAc)2 | t-AmOH | 10 | 3 | AgSbF6 | Cu(OAc)2 | DMF | 0 | 4 | AgSbF6 | Cu(OAc)2 | Dioxane | 8 | 5 | AgSbF6 | Cu(OAc)2 | THF | 21 | 6 | AgSbF6 | Cu(OAc)2 | MeCN | 0 | 7c | AgSbF6 | Cu(OAc)2 | DCE | 35 | 8d | AgSbF6 | Cu(OAc)2 | DCE | 82 | 9e | AgSbF6 | Cu(OAc)2 | DCE | 45 | 10d | Ag2CO3 | Cu(OAc)2 | DCE | 0 | 11d | AgOAc | Cu(OAc)2 | DCE | 20 | 12d | AgSbF6 | — | DCE | 0 | Open in a separate windowaReaction conditions: 1a (0.24 mmol), 2a (0.2 mmol), Ru(p-cymene)Cl2]2 (5 mol%), additive (20 mol%) and oxidant (2 equiv.) at 100 °C in a specific solvent (2.0 mL), under argon, for 16 h.bIsolated yields are of product 3aa.cThe reaction was performed at 120 °C.dThe reaction was performed at 80 °C.eThe reaction was performed at 60 °C. t-AmOH – tertiary amyl alcohol, DMF – N,N-dimethylformamide, DCE – 1,2-dichloroethane.The increase of temperature from 100 °C to 120 °C resulted in the formation of diene in lower yield (entry 7). To our delight, it was found that a substantial enhancement in the yield (82%) was observed when the reaction was performed at 80 °C (entry 8). In particular, this was found to be the best reaction condition since further lowering of the temperature led to noteworthy attenuation of the reaction rate and yield (entry 9). Interestingly, the reaction was not efficient, when AgSbF6 was replaced with other additives, such as Ag2CO3 and AgOAc. It was also observed that, co-oxidant Cu(OAc)2 is necessary for the success of this reaction (entry 12).With these optimized conditions in hand, various allyl sources and acrylates have been tested ( | Open in a separate windowaReaction conditions: 1 (0.24 mmol), 2 (0.2 mmol), Ru(p-cymene)Cl2]2 (5 mol%), AgSbF6 (20 mol%) and Cu(OAc)2·H2O (2 equiv.) at 80 °C in 1,2-dichloroethane (2.0 mL), under argon, 16 h.bIsolated yields are of product 3. TMS – trimethylsilyl, TBDMS – tertiarybutyldimethyl silyl.To extend the substrate scope of the reaction, we next examined the scope of allylesters by employing 2a as the coupling partner. First, we carried out the coupling reaction between allyl ester derivative 4a and methyl acrylate 2a under standard conditions. To our delight, a single isomer of acetate substituted (2E,4Z)-1,3-diene 5aa was isolated with a good yield (75%) ( Even for unsubstituted allyl esters very few reports of double bond migrations exist.59–62 It is worth mentioning that unlike the Tsuji–Trost reaction,63–65 the C(allyl)–O bond doesn''t break to form the π-allyl palladium complex as an electrophile, instead it forms a nucleophilic π-allylruthenium complex (umpolung reactivity) keeping the acetate group intact, which further reacts with an electrophile. The stereochemistry of the diene was established by 1D and 2D spectroscopic analysis of the compound 5ga and also by comparison of spectroscopic data with those of an authentic compound.66 Next we turned our attention to expand the scope of the coupling reaction between various acrylates and allyl esters. It was found that a variety of allyl esters bearing alkyl substituents on the carbonyl carbon could provide moderate to good yields of the corresponding stereodefined (2E,4Z)-1,3,4-trisubstituted 1,3-dienes successfully. As can be seen from |