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DOI: 10.1055/s-0031-1289758
Synthesis of Chromanes through RCM–Transfer Hydrogenation
Publication History
Received: 02 March 2012
Received after revision: 23 March 2012
Publication Date:
24 April 2012 (online)
Abstract
A sequential ruthenium-catalyzed ring-closing metathesis–transfer hydrogenation sequence has been established as a synthesis of chromanes starting from 2-(allyloxy)styrenes. The sequence requires only one precatalyst, the first-generation Grubbs catalyst, which is converted into a ruthenium hydride species in situ. Propan-2-ol serves as a chemical trigger for the formation of the ruthenium hydride and as hydrogen source.
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Biographical Sketches
Bernd Schmidt was born in 1967. He studied chemistry at the Technical University (RWTH) Aachen, where he received his diploma degree in 1991 and his Dr. rer nat. degree in 1994 under the supervision of Prof. G. E. Herberich with a thesis in the field of organoboron chemistry. In the same year he moved to the University of Southampton, UK, to join the group of Prof. Philip Kocienski as a postdoc, supported by the Deutsche Forschungsgemeinschaft. In 1996, Bernd Schmidt returned to Germany to start his independent academic career (supported by the Fonds der Chemischen Industrie and the Deutsche Forschungsgemeinschaft) at the Technical University (TU) Dortmund, associated with the group of Prof. P. Eilbracht. He became a lecturer at the TU Dortmund in 2001 and was appointed as professor for organic chemistry at the University of Potsdam in 2006. Since October 2010 he has been serving as vice dean for student and teaching affairs of the faculty of science of the University of Potsdam. His research interests are in the field of synthetic organic chemistry with a focus on transition-metal-catalyzed reactions, the development of new reaction sequences and the application of these methods in the synthesis of interesting natural and non-natural target molecules.
Stefan Krehl was born in Pritzwalk (Germany) in 1983. He studied chemistry at the University of Potsdam, where he finished his studies with a diploma thesis directed to the total synthesis of naturally occurring tubulysins under the guidance of Privatdozent Dr. Michael Sefkow. In 2008 he started experimental work towards his PhD under the guidance of Prof. Bernd Schmidt. To date, he has developed several assisted tandem catalytic sequences, in which a metathesis step and a non-metathesis step are catalysed by just one precatalyst.
Veronica Sotelo-Meza was born in 1987 in Lima, Peru. She received her Bachelor’s degree in Applied Chemistry from Georg August University (Göttingen, Germany) in 2010. She worked as a research assistant in the group of Prof. Schmidt under the supervision of Stefan Krehl at the University of Potsdam (Germany) in 2011. Currently, she is pursuing her M.Sc. degree in Applied Chemistry at the Free University of Berlin (Germany).
The discovery that ruthenium–carbene complexes can also catalyze a number of non-metathesis transformations[1] [2] [3] [4] has initiated the development of novel catalytic reaction sequences,[ 5,6 ] which can be described as assisted tandem catalytic reactions using the taxonomy proposed by Fogg and dos Santos.[ 7 ] Reaction sequences of this type rely on the connection of the catalytic cycle of the olefin metathesis reaction[ 8 ] with a different catalytic cycle by an organometallic transformation of the catalyst in situ.[ 9 ] This is triggered by a change in the reaction conditions or by the addition of suitable reagents, often referred to as ‘chemical triggers’.[ 7 ] These reactions are synthetically advantageous, because a metathesis reaction can be combined with the functionalization of the newly formed carbon–carbon double bond or the allylic position in one reaction vessel, using just one precatalyst and avoiding intermediate workup steps (Scheme [1]).
Along these lines ring-closing metathesis has been combined with ruthenium-catalyzed intramolecular Kharash reactions,[10] [11] Pauson–Khand reactions,[ 12 ] di- and ketohydroxylation,[13] [14] [15] [16] [17] cyclopropanation,[18] [19] or allylic oxidation.[20] [21] The latter sequence highlights an additional benefit of assisted tandem catalytic transformations, because it makes α,β-unsaturated lactones and lactams directly accessible from allyl ethers or amines, respectively, and thereby circumvents the notoriously difficult metathesis reaction of electron-deficient carbon–carbon double bonds. Normally, these require the more active and more expensive Schrock[ 22 ] or second-generation Grubbs catalysts[ 23 ] and rather high dilution.[ 24 ] Apart from the aforementioned RCM–non-metathesis reaction sequences, RCM–hydrogenation,[25] [26] [27] [28] [29] RCM–isomerization,[30] [31] [32] [33] and RCM–dehydrogenation[25] [34] have been described in the literature. The common feature of these transformations is that the second reaction is catalyzed by a ruthenium hydride,[ 2 ] which can result from a reaction of the metathesis catalyst with hydrogen,[35] [36] alcohols,[37] [38] [39] or enol ethers.[40] [41] [42]
Over the past few years, we have been particularly interested in the further development and application of the RCM–isomerization sequence (Scheme [2]).
This sequence, originally developed by Snapper et al.[ 30 ] and by one of us,[ 31 ] has emerged as a useful method for the synthesis of cyclic enol ethers 3 from allyl ethers 1. It has, for instance, been applied to the synthesis of diarylheptanoid natural products,[43] [44] [45] deoxygenated carbohydrates,[ 46–48 ] C-aryl glycosides,[49] [50] or 2-arylfurans.[ 51 ] Among the protocols developed in our group, the use of sub-stoichiometric amounts of solid sodium hydride, sodium borohydride,[ 31 ] or sodium hydroxide and propan-2-ol as additives[ 32 ] was found to trigger the conversion of the Ru–carbene into a Ru–hydride very efficiently. This enabled the highly regioselective synthesis of numerous five- to eight-membered cyclic enol ethers. In only very few cases the formation of saturated oxacycles 4 as byproducts was observed when sodium hydride and propan-2-ol were used as additives. This side reaction can be attributed to a ruthenium-catalyzed hydrogen transfer from the co-solvent propan-2-ol to the isomerized product 3. In all cases, we found that the double bond migration leading from the initial RCM product 2 to the isomerized product 3 is much faster than the hydrogenation leading to 4. It is in line with this observation, that the formation of saturated products 4 could be suppressed by lowering the reaction temperature.[33] [52] While numerous examples for the ruthenium-catalyzed transfer dehydrogenation of alcohols and transfer hydrogenation of aldehydes and ketones have been reported in the literature,[34] [53] [54] [55] the hydrogenation of carbon–carbon double bonds is less common. In most of these examples, the alkene primarily serves as a hydrogen scavenger to accelerate the ruthenium-catalyzed dehydrogenation of alcohols to aldehydes or ketones.[ 53 ]
We discovered a case of exceptionally strongly preferred transfer hydrogenation of unsaturated oxacycles in the course of a project directed at the synthesis of 4H-chromenes 7 from 2-(allyloxy)styrenes 5, using the RCM–isomerization sequence (Scheme [3]). 4H-Chromenes have previously been synthesized by RCM of enol ethers[56] [57] [58] or by elimination of lactols.[ 59 ] They are interesting natural products themselves,[ 59 ] or synthetic intermediates en route to other target molecules, in particular flavans.[ 58 ] It was expected that the isomerization of the initially formed 2H-chromenes 6 to 4H-chromenes 7 would be thermodynamically less favorable or even impossible, considering that the conjugation of the carbon–carbon double bond with the aromatic system is disrupted in the process. However, we could not find unambiguous experimental evidence in the literature to decide beforehand whether or not the isomerization of 6 to 7 is feasible. For these reasons, precursor 5a was subjected to the conditions of the RCM–isomerization sequence, using sodium hydride as the chemical trigger to induce the in situ conversion into the isomerization catalyst. NMR spectroscopy of the crude reaction mixture revealed, that a significant proportion of the desired 4H-chromene 7a was present, but that several unidentified byproducts were formed that could not be completely removed even after repeated chromatography. A virtually identical outcome was observed for the 8-ethoxy derivative 5c. These results showed that the isomerization of 2H- to 4H-chromenes is, in principle, possible, but that an improvement of the selectivity of the isomerization step was required. We suspected that an overly long reaction time might be the origin of the insufficient selectivity, and we knew from our previous experience that in many cases the isomerization step is significantly accelerated by switching from sodium hydride or sodium borohydride as chemical triggers to sodium hydroxide and propan-2-ol. In light of the rather scarce literature precedence for hydrogen transfer from alcohols to alkenes, we were surprised to find that under these conditions 2-(allyloxy)styrene (5a) did not undergo RCM–isomerization to the 4H-chromene 7a. Instead, only chromane 8a was formed, which could be isolated from the reaction mixture in 66% yield (Scheme [3]).
This interesting and hitherto unprecedented outcome of an attempted RCM–isomerization sequence prompted us to investigate the reaction of other 2-(allyloxy)styrenes under these reaction conditions in more detail. The ring-closing metathesis of various allyl 2-vinylphenyl ethers to chromenes 6 was previously investigated by Grubbs et al.[ 60 ] Apart from the mechanistic relevance, a selective RCM–transfer hydrogenation leading to chromanes might also be synthetically useful, because the chromane skeleton is found in numerous drugs, such as nebivolol, a β-blocker, or the antidiabetic drug englitazone.[ 61 ] In addition, chromanes have been synthesized and tested as plant growth inhibitors[62] [63] or as inhibitors of uncoupling proteins.[ 64 ] The inhibition of uncoupling proteins (UCPs) in tumor cells can increase oxidative stress, and therefore UCP inhibitors are considered as synergistic drugs in chemotherapy, in particular to overcome chemoresistance. Consequently, there has been a continuous interest in the development of methods for the synthesis of chromanes, as exemplified by a recent contribution describing the indium-catalyzed intramolecular arylation of homoallyl ethers.[ 65 ]
a Yield based on aldehyde or ketone 9.
We started with the synthesis of several metathesis precursors 5 [ 60 ] from the commercially available salicylaldehydes or acetophenones 9. Allylation of the phenol was achieved with allyl bromide in the presence of potassium carbonate as a base. The resulting allyl ethers 10 were converted into the required 2-(allyloxy)styrenes 5 by Wittig olefination with methylenetriphenylphosphorane, obtained in situ by deprotonation of methyltriphenylphosphonium bromide with sodium hydride (Table [1]).
Remarkably, this sequence failed completely for the synthesis of a nitro-substituted derivative 5i. However, this problem could be solved by inverting the order of steps. Thus, 9i was first converted into styrene 11i,[ 66 ] which was then O-allylated under standard conditions to give the desired metathesis precursor 5i in more than 70% yield (Scheme [4]).
Another derivative, 1-(allyloxy)-2,4-divinylbenzene (5j), was synthesized from 5d via bromine–lithium exchange, followed by reaction with N,N-dimethylformamide and Wittig olefination of the intermediate aldehyde 5k in 80% overall yield. Remarkably, the allyl ether is not affected by the organolithium reagent required for the halogen–metal exchange, although a less reactive aryl bromide is used (Scheme [5]).
In the next step, metathesis precursors 5b–j were subjected to the conditions established for the conversion of 5a into chromane 8a. With very few exceptions a smooth conversion into the substituted chromanes 8 was observed, which could be isolated in preparatively useful yields. The results are summarized in Table [2]. Remarkably, the 4-methyl-substituted chromanes 8f and 8g were both obtained in good yields under standard conditions (entries 6 and 7). This is noteworthy, because similar substrates with one geminally disubstituted double bond, which are not benzoannulated, were previously found to be inert towards double bond migration and transfer hydrogenation under the conditions of the RCM–isomerization sequence triggered by the additive combination of propan-2-ol and sodium hydroxide.[ 33 ] In these cases, only the products of the ring-closing metathesis reaction were isolated. Considering the good results obtained for 4-methyl-substituted chromanes 8f and 8g, and also those for 6-bromochromane 8d (entry 4), we were surprised to find that 4-methyl-6-bromochromane 8h (entry 8) is not accessible via this sequence. Repeated attempts to convert the appropriate precursor 5h into 8h resulted reproducibly in a complex mixture of unidentified products. The reactions of two further derivatives deserve a special comment. In the case of the nitro-substituted precursor 5i we were particularly interested to see if a subsequent or concurrent reduction of the nitro group occurred under the RCM–transfer hydrogenation conditions. We could indeed isolate a primary amine in a rather low yield of 33%, which, however, was identified as chromene 12 (entry 9). This result suggests that a fast ruthenium-catalyzed reduction of the nitro group occurs, but that the catalytically active species is inhibited by the primary amine accumulating in the reaction mixture, thereby explaining the incomplete conversion and the low yield of 12. This observation also implies that the transfer hydrogenation of the alkene is significantly slower than the reduction of the nitro group. In the case of triene 5j (entry 10) 6-ethylchromane 8j was the sole product. No partially hydrogenated products were observed in the course of the reaction, leading to the assumption that the endocyclic double bond resulting from the RCM step and the vinyl group are concurrently hydrogenated.
The unusual preference for RCM–transfer hydrogenation over RCM–isomerization in the case of 2-(allyloxy)styrenes 5 can be rationalized by a comparison of the tentative mechanisms (Scheme [6]). After completion of the ring-closing metathesis of 5 to chromene 6 the catalytically active Ru–carbene species A′ reacts to a Ru–hydride B, triggered by the reaction with the co-solvent propan-2-ol and hydroxide. NMR spectroscopic evidence for the formation of a Ru–hydride complex under these conditions has previously been presented by one of us.[ 33 ] The transition-metal–hydride catalyzed double bond isomerization of alkenes proceeds via a hydrometalation–β-hydride elimination mechanism,[ 67 ] which has been shown to operate for Ru–hydrides by Grubbs and McGrath using isotopic labeling experiments.[ 68 ]
a Precursor 5 (0.1 M in toluene), catalyst A (5 mol%), 40 °C; then add i-PrOH (10 vol%), NaOH (s, 0.5 equiv), 110 °C.
b Complex mixture of products.
In the case of 2H-chromenes 6, double bond isomerization to the cyclic enol ethers 7 requires a regioselective insertion of the carbon–carbon double bond into the Ru–hydride, giving the σ-complex C, which will then undergo a β-hydride elimination to π-complex D. Dissociation liberates the isomerized product 7 and regenerates the catalyst B. A factor contributing to the discrimination of the isomerization pathway in this particular case is most likely a lower thermodynamic driving force, because the carbon–carbon double bond will be shifted out of the conjugation with the aromatic system. We assume, however, that an additional factor contributes even stronger to the observed selectivity. Presumably, the regioselectivity of the hydroruthenation of chromenes 6 will be biased by electronic factors, leading to the preferred formation of a σ-η1-benzyl ruthenium intermediate E, which will most likely undergo a haptotropic rearrangement to a π-η3-benzyl ruthenium complex F. The involvement of analogous π-η3-benzyl-rhodium[ 67 ] and -palladium[ 68 ] intermediates has been proposed as an explanation for the very high regioselectivities observed for rhodium-catalyzed hydroboration and palladium-catalyzed hydroamination of styrenes. This proposal is further substantiated by X-ray single crystal structure analysis data[ 68 ] and theoretical considerations.[ 69 ] From intermediate F, the catalytic cycle can continue by addition of propan-2-ol to the ruthenium complex with formation of a Ru–hydride G, which then undergoes reductive elimination of the hydrogenated product 8. From the resulting alkoxide H, the catalytically active Ru–hydride B is regenerated by β-hydride elimination with concomitant formation of acetone. Alternatively, F is protonated by propan-2-ol, which would directly result in the formation of 8 and alkoxide H.
In summary, we describe a highly selective RCM–transfer hydrogenation of 2-(allyloxy)styrenes under conditions that normally induce RCM–isomerization. Through the sequence described herein, a variety of substituted chromanes becomes accessible in a convenient way without using hydrogen gas. Instead, propan-2-ol in the presence of hydroxide serves as a chemical trigger for the in situ formation of the transfer hydrogenation catalyst and as a hydrogen transfer reagent.
All experiments were conducted in dry reaction vessels under an atmosphere of dry N2. Solvents were purified by standard procedures. 1H NMR spectra were obtained at 300 MHz in CDCl3 with TMS (δ = 0.00 ppm) or CHCl3 (δ = 7.26 ppm) as an internal standard. 13C NMR spectra were recorded at 75 MHz in CDCl3 with CDCl3 (δ = 77.0 ppm) as an internal standard. IR spectra were recorded in substance on NaCl or KBr plates. Mass spectra were obtained at 70 eV. First-generation Grubbs catalyst (A)[ 70 ] was purchased and used in all experiments without further purification.
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Attempted Synthesis of 4H-Chromene (7a); Typical Procedure
To a soln of 5a (960 mg, 6.0 mmol) in toluene (20 mL) was added catalyst A (250 mg, 5 mol%). The mixture was stirred at 40 °C for 2 h, and NaH (100 mg of a 60% dispersion in mineral oil, 2.5 mmol) was added. The mixture was then heated to reflux for 6 h, cooled to r.t. and quenched by addition of H2O. The organic layer was separated, the aqueous layer was extracted with MTBE, and the combined organic extracts were dried (MgSO4), filtered, and evaporated. NMR spectroscopy of the crude reaction mixture revealed the presence of 7a along with unidentified byproducts. Selected data for 7a (obtained from the spectrum of the crude mixture):
1H NMR (300 MHz, C6D6): δ = 6.95–6.68 (4 H), 6.29 (d, J = 6.5 Hz, 1 H), 4.56 (dt, J = 6.5, 3.5, 3.5 Hz, 1 H), 3.07 (m, 2 H).
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Attempted Synthesis of 8-Ethoxy-4H-chromene (7c)
Precursor 5c (204 mg, 1.0 mmol) was subjected to conditions analogous to those stated above for the RCM isomerization of 5a. NMR spectroscopy of the crude reaction mixture revealed the presence of 7c, along with several unidentified byproducts. Selected data for 7c (obtained from the spectrum of the crude mixture) follows.
1H NMR (300 MHz, CDCl3): δ = 6.92–6.75 (3 H), 6.74 (d, J = 6.5 Hz, 1 H), 4.93 (dt, J = 6.5, 3.5, 3.5 Hz, 1 H), 4.06 (q, J = 7.0 Hz, 2 H), 3.37 (m, 2 H), 1.45 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 147.6, 147.0, 140.5, 129.8, 122.6, 120.9, 111.1, 100.2, 64.3, 22.9, 14.7.
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RCM–Transfer Hydrogenation; General Procedure
To a soln of the appropriate ether 5 (1.0 mmol) in toluene (10.0 mL) was added catalyst A (41.1 mg, 5 mol%). The mixture was stirred at 40 °C for 2 h, then powdered NaOH (20 mg, 0.5 mmol) and i-PrOH (1.0 mL) were added. This soln was heated to 100 °C for an additional 4.5 h. After cooling to r.t. it was filtered through a short pad of silica. The pad of silica was washed with MTBE (75 mL), and all volatiles were removed in vacuo. The residue was purified by column chromatography (silica gel).
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3,4-Dihydro-2H-chromene (8a)[ 71 ]
Following the general procedure using 5a (160 mg, 1.0 mmol) gave 8a (88 mg, 66%) as a colorless liquid.
IR (neat): 2934 (m), 1866 (w), 1607 (m), 1581 (m), 1488 (s), 1455 (m), 1303 (w), 1266 (m), 1227 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.11–6.99 (2 H), 6.87–6.75 (2 H), 4.18 (t, J = 5.2 Hz, 2 H), 2.78 (t, J = 6.5 Hz, 2 H), 2.00 (tt, J = 6.5, 5.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 154.9, 129.8, 127.2, 122.2, 120.1, 116.7, 66.4, 24.9, 22.4.
MS (EI): m/z (%) = 134 (M+, 78), 133 (80), 313 (100), 118 (32), 105 (25), 91 (38), 78 (30), 77 (38).
HRMS (EI): m/z [M]+ calcd for C9H10O: 134.0732; found: 134.0731.
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8-Methoxy-3,4-dihydro-2H-chromene (8b)[ 72 ]
Following the general procedure using 5b (190 mg, 1.0 mmol) gave 8b (136 mg, 82%) as a colorless liquid.
IR (neat): 2933 (w), 2838 (w), 1583 (m), 1484 (s), 1333 (m), 1259 (s), 1218 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 6.83–6.62 (3 H), 4.27 (t, J = 6.5 Hz, 2 H), 3.86 (s, 3 H), 2.79 (t, J = 6.5 Hz, 2 H), 2.09–1.94 (2 H).
13C NMR (75 MHz, CDCl3) δ = 148.3, 144.2, 122.8, 121.7, 119.5, 108.9, 66.8, 55.7, 24.7, 22.2.
MS (EI): m/z (%) = 164 (M+, 100), 149 (20), 136 (12), 135 (13), 121 (10).
HRMS (EI): m/z [M]+ calcd for C10H12O2: 164.0837; found: 164.0840.
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8-Ethoxy-3,4-dihydro-2H-chromene (8c)
Following the general procedure using 5c (204 mg, 1.0 mmol) gave 8c (176 mg, 98%) as a colorless liquid.
IR (neat): 2975 (w), 2930 (w), 2870 (m), 1582 (m), 1478 (s), 1392 (w), 1333 (m), 1259 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 6.77 (dd, J = 8.0, 7.3 Hz, 1 H), 6.72 (dd, J = 8.0, 1.9 Hz, 1 H), 6.66 (m, 1 H), 4.28 (t, J = 5.2 Hz, 2 H), 4.10 (q, J = 7.0 Hz, 2 H), 2.80 (t, J = 6.5 Hz, 2 H), 2.06–1.97 (2 H), 1.48 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 147.5, 144.4, 122.8, 121.5, 119.3, 110.2, 66.6, 63.9, 24.7, 22.0, 14.7.
MS (EI): m/z (%) = 178 (M+, 100), 150 (75), 122 (66).
HRMS (EI): m/z [M]+ calcd for C11H14O2: 178.0994; found: 178.0988.
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6-Bromo-3,4-dihydro-2H-chromene (8d)
Following the general procedure using 5d (239 mg, 1.0 mmol) gave 8d (137mg, 65%) as a colorless liquid.
IR (neat): 2936 (m), 2872 (m), 1756 (w), 1483 (s), 1261 (m), 1228 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.19–7.11 (2 H), 6.66 (d, J = 9.3 Hz, 1 H), 4.15 (t, J = 5.2 Hz, 2 H), 2.75 (t, J = 6.5 Hz, 2 H), 1.97 (tt, J = 6.5, 5.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 154.1, 132.2, 130.0, 124.3, 118.5, 112.0, 66.4, 24.7, 22.0.
MS (EI): m/z (%) = 214 (M+, 100), 212 (M+, 98), 199 (30), 133 (46), 118 (40), 105 (60), 77 (75), 69 (50).
HRMS (EI): m/z [M]+ calcd for C9H9O[79]Br: 211.9837; found: 211.9846.
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2,3-Dihydro-1H-benzo[f]chromene (8e)[ 73 ]
Following the general procedure using 5e (210 mg, 1.0 mmol) gave 8e (138 mg, 75%) as a colorless solid; mp 35–37 °C.
IR (neat): 3059 (w), 2931 (w), 2871 (w), 1621 (m), 1596 (m), 1514 (m), 1472 (m), 1372 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 7.75 (d, J = 9.1 Hz, 1 H), 7.72 (d, J = 8.7 Hz, 1 H), 7.58 (d, J = 8.9 Hz, 1 H), 7.45 (m, 1 H), 7.30 (m, 1 H), 7.03 (d, J = 8.9 Hz, 1 H), 4.20 (t, J = 5.2 Hz, 2 H), 2.98 (t, J = 6.6 Hz, 2 H), 1.97 (tt, J = 6.5, 5.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 152.5, 133.2, 129.0, 128.3, 127.5, 126.2, 123.1, 121.7, 119.0, 113.8, 66.1, 22.2, 21.2.
MS (EI): m/z (%) = 184 (M+, 100), 128 (55).
HRMS (EI): m/z [M]+ calcd for C13H12O: 184.0888; found: 184.0886.
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4-Methyl-3,4-dihydro-2H-chromene (8f)[ 65 ]
Following the general procedure using 5f (174 mg, 1.0 mmol) gave 8f (92 mg, 62%) as a colorless liquid.
IR (neat): 2960 (m), 2873 (w), 1606 (w), 1580 (w), 1488 (s), 1447 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 7.20 (br d, J = 7.6 Hz, 1 H), 7.13 (m, 1 H), 6.91 (ddd, J = 8.7, 7.5, 1.2 Hz, 1 H), 6.85 (dd, J = 8.2, 1.1 Hz, 1 H), 4.25 (ddd, J = 10.9, 4.0, 3.4 Hz, 1 H), 4.20 (ddd, J = 10.9, 3.6, 3.0 Hz, 1 H), 2.99 (m, 1 H), 2.13 (dddd, J = 13.3, 5.8, 4.2, 3.6 Hz, 1 H), 1.76 (dddd, J = 13.1, 7.0, 6.5, 3.6 Hz, 1 H), 1.38 (d, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 154.3, 128.6, 127.6, 127.1, 120.1, 116.7, 63.8, 30.3, 28.5, 22.1.
MS (EI): m/z (%) = 148 (M+, 54), 133 (100), 121 (64), 105 (40), 91 (48), 77 (32), 57 (40), 43 (52).
HRMS (EI): m/z [M]+ calcd for C10H12O: 148.0888; found: 148.0894.
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4,6-Dimethyl-3,4-dihydro-2H-chromene (8g)[ 65 ]
Following the general procedure using 5g (188 mg, 1.0 mmol) gave 8g (136 mg, 83%) as a colorless liquid.
IR (neat): 2960 (m), 2873 (w), 1606 (w), 1580 (w), 1488 (s), 1447 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 6.99 (br s, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 4.25 (ddd, J = 10.9, 4.1, 3.3 Hz, 1 H), 4.18 (ddd, J = 10.9, 3.6, 3.0 Hz, 1 H), 2.96 (m, 1 H), 2.31 (s, 3 H), 2.13 (dddd, J = 13.0, 6.7, 5.9, 3.7 Hz, 1 H), 1.76 (dddd, J = 13.0, 7.2, 6.6, 3.0 Hz, 1 H), 1.37 (d, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 152.1, 129.2, 129.0, 127.8, 127.2, 116.4, 63.8, 30.5, 28.5, 22.2, 20.6.
MS (EI): m/z (%) = 162 (M+, 65), 147 (100), 119 (32), 91 (18).
HRMS (EI): m/z [M]+ calcd for C11H14O: 162.1045; found: 162.1047.
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6-Ethyl-3,4-dihydro-2H-chromene (8j)
Following the general procedure using 5j (186 mg, 1.0 mmol) gave 8j (123 mg, 76%) as a colorless liquid.
IR (neat): 2961 (m), 2865 (m), 1586 (w), 1500 (s), 1304 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 6.95 (dd, J = 8.2, 2.1 Hz, 1 H), 6.89 (br s, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 4.19 (t, J = 5.2 Hz, 2 H), 2.80 (t, J = 6.5 Hz, 2 H), 2.58 (q, J = 7.6 Hz, 2 H), 2.02 (tt, J = 6.5, 5.2 Hz, 2 H), 1.23 (t, J = 7.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 152.9, 135.8, 128.9, 126.6, 121.8, 116.5, 66.3, 28.0, 24.9, 22.5, 15.8.
MS (EI): m/z (%) = 162 (M+, 65), 147 (100), 119 (32), 91 (18).
HRMS (EI): m/z [M]+ calcd for C11H14O: 162.1045; found: 162.1047.
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2H-Chromen-6-amine (12)
Following the general procedure using 5i (205 mg, 1.0 mmol) gave 12 (49 mg, 33%) as a colorless liquid.
IR (neat): 3422 (m), 3550 (m), 3220 (w), 3046 (w), 2960 (w), 2826 (m), 1624 (m), 1491 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 6.62 (d, J = 8.4 Hz, 1 H), 6.46 (dd, J = 8.4, 2.4 Hz, 1 H), 6.40–6.32 (2 H), 5.79 (ddd, J = 9.8, 3.6, 3.6 Hz, 1 H), 4.71 (dd, J = 3.7, 1.9 Hz, 2 H), 3.14 (br s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 146.9, 140.4, 124.7, 123.1, 122.8, 116.1, 115.8, 113.5, 65.3.
MS (EI): m/z (%) = 147 (M+, 100), 146 (80), 118 (32), 117 (16), 91 (12).
HRMS (EI): m/z [M]+ calcd for C9H9NO: 147.0684; found: 147.0685.
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Metathesis Precursors 5; General Procedure
To a soln of the appropriate phenol 9 in acetone (3.0 mL/mmol) were added K2CO3 (2.0 equiv) and allyl bromide (2.0 equiv). The suspension was stirred at 60 °C until the starting material was fully consumed, as indicated by TLC (approx. 3 h). After cooling to r.t., the mixture was filtered through a short pad of Celite, which was subsequently washed with acetone (50 mL). After evaporation of all volatiles in vacuo, the crude aldehyde or ketone 10 was directly used in the next step without further purification.
To a suspension of NaH (60% dispersion in mineral oil, 1.5 equiv) in THF (3.0 mL/mmol) was added [Ph3PCH3]Br (1.25 equiv). The suspension was stirred at 60 °C for 1 h. After cooling to r.t., a soln of the appropriate crude aldehyde or ketone 10 from the previous step in THF (1.0 mL/mmol) was added dropwise. The mixture was stirred until the aldehyde or ketone 10 was fully consumed as indicated by TLC (approx. 3 h). It was filtered through a short pad of Celite, which was washed with MTBE (50 mL). All volatiles were removed in vacuo, the residue was redissolved in a minimum volume of CH2Cl2 and filtered through a silica gel column. After evaporation of the solvent the residue was purified by column chromatography (silica gel).
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1-(Allyloxy)-2-vinylbenzene (5a)[ 60 ]
Following the general procedure using 9a gave 5a (4.32 g, 90%) as a colorless liquid.
IR (neat): 3080 (w), 2922 (w), 1599 (m), 1489 (s), 1452 (s), 1240 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.47 (dd, J = 7.6, 1.5 Hz, 1 H), 7.19 (m, 1 H), 7.10 (dd, J = 17.8, 11.2 Hz, 1 H), 6.91 (dd, J = 7.5, 7.5 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 1 H), 6.05 (ddt, J = 17.2, 10.4, 5.1 Hz, 1 H), 5.74 (dddd, J = 17.8, 1.5, 1.5, 1.5 Hz, 1 H), 5.40 (dddd, J = 17.2, 1.6, 1.5, 1.5 Hz, 1 H), 5.32–5.15 (2 H), 4.53 (ddd, J = 5.1, 1.4, 1.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 155.7, 133.3, 131.6, 128.7, 127.1, 126.5, 120.8, 117.2, 114.3, 112.3, 69.1.
MS (EI): m/z (%) = 160 (M+, 6), 119 (6), 91 (12), 85 (18), 83 (23), 50 (17), 44 (20), 38 (29), 36 (100).
HRMS (EI): m/z [M]+ calcd for C11H12O: 160.0883; found: 160.0873.
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2-(Allyloxy)-1-methoxy-3-vinylbenzene (5b)[ 60 ]
Following the general procedure using 9b gave 5b (3.65 g, 96%) as a colorless liquid.
IR (neat): 3083 (w), 2936 (w), 2836 (w), 1575 (m), 1474 (s), 1439 (m), 1412 (m), 1265 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.40 (d, J = 8.5 Hz, 1 H), 6.99 (dd, J = 17.8, 11.2 Hz, 1 H), 6.48 (dd, J = 8.5, 2.4 Hz, 1 H), 6.42 (d, J = 2.4 Hz, 1 H), 6.06 (ddt, J = 17.3, 10.4, 5.1 Hz, 1 H), 5.63 (dd, J = 17.8, 1.6 Hz, 1 H), 5.42 (dddd, J = 17.3, 1.6, 1.5, 1.5 Hz, 1 H), 5.28 (dddd, J = 10.5, 1.4, 1.4, 1.4 Hz, 1 H), 5.14 (dd, J = 11.2, 1.6 Hz, 1 H), 4.53 (ddd, J = 5.1, 1.5, 1.5 Hz, 2 H), 3.79 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 160.4, 156.8, 133.2, 131.3, 127.2, 120.2, 117.3, 112.1, 105.2, 99.7, 69.2, 55.3.
MS (EI): m/z (%) = 190 (M+, 29), 149 (41), 121 (100), 105 (25), 91 (52), 78 (34).
HRMS (EI): m/z [M]+ calcd for C12H14O2: 190.0988; found: 190.0975.
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2-(Allyloxy)-1-ethoxy-3-vinylbenzene (5c)
Following the general procedure using 9c gave 5c (4.10 g, 80%) as a colorless liquid.
IR (neat): 2979 (w), 1574 (m), 1464 (m), 1265 (s), 1203 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 7.11 (m, 1 H), 7.09 (dd, J = 17.8, 11.0 Hz, 1 H), 6.98 (dd, J = 8.0, 8.0 Hz, 1 H), 6.80 (dd, J = 8.0, 1.4 Hz, 1 H), 6.10 (m, 1 H), 5.73 (dd, J = 17.8, 1.3 Hz, 1 H), 5.35 (dddd, J = 17.2, 1.4, 1.3, 1.3 Hz, 1 H), 5.27 (dd, J = 11.1, 1.3 Hz, 1 H), 5.21 (m, 1 H), 4.52–4.47 (2 H), 4.05 (q, J = 7.0 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 152.3, 145.9, 134.5, 132.1, 131.6, 123.8, 117.8, 117.2, 114.8, 113.0, 74.0, 64.3, 14.9.
MS (EI): m/z (%) = 204 (M+, 21), 135 (50), 107 (57), 105 (22), 83 (44), 36 (100).
HRMS (EI): m/z [M]+ calcd for C13H16O2: 204.1145; found: 204.1158.
Anal. Calcd for C13H16O2 (204.26): C, 76.44; H, 7.90. Found: C, 75.95; H, 8.25.
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1-(Allyloxy)-4-bromo-2-vinylbenzene (5d)[ 60 ]
Following the general procedure using 9d gave 5d (2.56 g, 71%) as a colorless liquid.
IR (neat): 3085 (w), 2922 (w), 1479 (s), 1410 (m), 1240 (s), 1121 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 7.57 (d, J = 2.5 Hz, 1 H), 7.28 (dd, J = 8.8, 2.5 Hz, 1 H), 7.00 (dd, J = 17.7, 11.1 Hz, 1 H), 6.71 (d, J = 8.8 Hz, 1 H), 6.04 (ddt, J = 17.2, 10.4, 5.1 Hz, 1 H), 5.73 (dd, J = 17.9, 0.9 Hz, 1 H), 5.40 (dddd, J = 17.2, 1.6, 1.4, 1.4 Hz, 1 H), 5.29 (dd, J = 11.1, 1.1 Hz, 1 H), 5.29 (dddd, J = 10.6, 1.3, 1.3, 1.3 Hz, 1 H), 4.52 (ddd, J = 5.1, 1.5, 1.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 154.7, 132.8, 131.1, 130.4, 130.4, 129.1, 117.6, 115.6, 114.0, 113.3, 69.3.
MS (EI): m/z (%) = 240 (M+, 14), 238 (M+, 16), 159 (14), 118 (100), 97 (15), 90 (21), 89 (29), 85 (36), 83 (52), 71 (26), 41 (78).
HRMS (EI): m/z [M]+ calcd for C11H11O[79]Br: 237.9988; found: 239.9971.
#
2-(Allyloxy)-1-vinylnaphthalene (5e)[ 60 ]
Following the general procedure using 9e gave 5e (4.40 g, 84%) as a yellow liquid.
IR (neat): 3080 (w), 2864 (w), 1590 (m), 1264 (s), 1243 (s), 1220 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 8.19 (d, J = 8.6 Hz, 1 H), 7.76 (d, J = 8.6 Hz, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.45 (ddd, J = 8.4, 6.8, 1.3 Hz, 1 H), 7.34 (m, 1 H), 7.23 (d, J = 9.0 Hz, 1 H), 7.12 (dd, J = 17.9, 11.7 Hz, 1 H), 6.09 (ddt, J = 17.2, 10.3, 5.1 Hz, 1 H), 5.77 (dd, J = 18.0, 2.2 Hz, 1 H), 5.74 (dd, J = 11.6, 2.2 Hz, 1 H), 5.44 (dddd, J = 17.2, 1.6, 1.6, 1.6 Hz, 1 H), 5.27 (dddd, J = 17.2, 1.4, 1.4, 1.4 Hz, 1 H), 4.68 (ddd, J = 5.1, 1.5, 1.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 153.4, 133.6, 132.4, 130.3, 129.4, 128.7, 128.2, 126.3, 124.3, 123.6, 122.0, 120.6, 117.2, 114.9, 70.1.
MS (EI): m/z (%) = 210 (M+, 39), 169 (41), 141 (100), 139 (33), 115 (47), 71 (24), 69 (20), 57 (36), 55 (34), 44 (37), 41 (44), 39 (29).
HRMS (EI): m/z [M]+ calcd for C15H14O: 210.1039; found: 210.1052.
#
1-(Allyloxy)-2-(prop-1-en-2-yl)benzene (5f)[ 74 ]
Following the general procedure using 9f gave 5f (4.00 g, 92%) as a colorless liquid.
IR (neat): 3078 (w), 2918 (w), 1597 (m), 1488 (m), 1445 (m), 1232 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.22–7.15 (2 H), 6.90 (ddd, J = 7.4, 7.4, 1.1 Hz, 1 H), 6.84 (dd, J = 8.7, 0.9 Hz, 1 H), 6.03 (ddt, J = 17.3, 10.4, 5.1 Hz, 1 H), 5.39 (dddd, J = 17.3, 1.7, 1.7, 1.7 Hz, 1 H), 5.24 (dddd, J = 10.6, 1.5, 1.5, 1.5 Hz, 1 H), 5.13 (m, 1 H), 5.07 (m, 1 H), 4.53 (ddd, J = 5.1, 1.6, 1.6 Hz, 2 H), 2.13 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 155.7, 144.2, 133.5, 133.3, 129.5, 128.2, 120.8, 117.0, 115.0, 112.5, 69.2, 23.2.
MS (EI): m/z (%) = 174 (M+, 8), 159 (21), 144 (21), 133 (77), 131 (41), 105 (100), 103 (33), 83 (53), 77 (51), 41 (59), 39 (52).
HRMS (EI): m/z [M]+ calcd for C12H14O: 174.1039; found: 174.1049.
#
1-(Allyloxy)-4-methyl-2-(prop-1-en-2-yl)benzene (5g)[ 74 ]
Following the general procedure using 9g gave 5g (3.32 g, 88%) as a colorless liquid.
IR (neat): 3080 (w), 2919 (w), 1632 (w), 1495 (s), 1232 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.01 (s, 1 H), 7.00 (m, 1 H), 6.76 (d, J = 8.9 Hz, 1 H), 6.04 (ddt, J = 17.2, 10.4, 5.1 Hz, 1 H), 5.38 (dddd, J = 17.3, 1.6, 1.6, 1.6 Hz, 1 H), 5.24 (m, 1 H), 5.12 (m, 1 H), 5.06 (m, 1 H), 4.52 (ddd, J = 5.1, 1.5, 1.5 Hz, 2 H), 2.28 (s, 3 H), 2.13 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 153.6, 144.3, 133.7, 133.1, 130.2, 130.0, 128.4, 116.9, 114.8, 112.8, 69.4, 23.2, 20.4.
MS (EI): m/z (%) = 188 (M+, 12), 173 (11), 147 (28), 145 (16), 119 (48), 85 (66), 83 (100).
HRMS (EI): m/z [M]+ calcd for C13H16O: 188.1196; found: 188.1199.
Anal. Calcd for C13H16O (188.27): C, 82.94; H, 8.57. Found: C, 83.00; H, 8.74.
#
1-(Allyloxy)-4-bromo-2-(prop-1-en-2-yl)benzene (5h)
Following the general procedure using 9h gave 5h (5.60 g, 89%) as a colorless liquid.
IR (neat): 3081 (w), 2919 (w), 1633 (w), 1483 (s), 1424 (m), 1233 (s), 1098 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 7.30 (s, 1 H), 7.28 (m, 1 H), 6.71 (m, 1 H), 6.02 (ddt, J = 17.2, 10.4, 5.1 Hz, 1 H), 5.38 (dddd, J = 17.3, 1.6, 1.6, 1.6 Hz, 1 H), 5.26 (dddd, J = 10.6, 1.4, 1.4, 1.4 Hz, 1 H), 5.15 (m, 1 H), 5.07 (m, 1 H), 4.52 (ddd, J = 5.1, 1.6, 1.6 Hz, 2 H), 2.10 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 154.8, 142.9, 135.3, 133.0, 132.1, 130.7, 117.4, 116.0, 114.2, 113.0, 69.4, 22.9.
MS (EI): m/z (%) = 188 254 (M+, 9), 252 (M+, 10), 213 (17), 211 (24), 158 (23), 132 (100), 131 (68), 104 (14), 103 (17).
HRMS (EI): m/z [M]+ calcd for C12H13O[79]Br: 252.0144; found: 252.0162.
Anal. Calcd for C12H13OBr (253.14): C, 56.94; H, 5.18. Found: C, 56.94; H, 5.25.
#
4-Nitro-2-vinylphenol (11i)[ 75 ]
To a suspension of NaH (60% dispersion in mineral oil, 420 mg, 10.5 mmol) in THF (9.0 mL) was added [Ph3PCH3]Br (4.18 g, 11.7 mmol). The suspension was stirred at 60 °C for 1 h. After cooling to r.t., a soln of aldehyde 9i (501 mg, 3.0 mmol) in THF (1.0 mL) was added dropwise. The mixture was stirred until the starting material was fully consumed as indicated by TLC (approx. 3 h). It was filtered through a short pad of Celite, which was washed with MTBE (50 mL). All volatiles were removed in vacuo, the residue was redissolved in a minimum volume of CH2Cl2 and filtered through a silica gel column. After evaporation of the solvent the residue was purified via column chromatography to give styrene 11i (400 mg, 81%) as a yellow solid; mp 80–81 °C.
IR (neat): 3372 (m), 1584 (m), 1517 (m), 1329 (s), 1277 (s), 1220 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 8.31 (d, J = 2.7 Hz, 1 H), 8.04 (dd, J = 9.0, 2.7 Hz, 1 H), 6.93 (d, J = 8.9 Hz, 1 H), 6.94 (dd, J = 17.7, 11.2 Hz, 1 H), 6.74 (br s), 5.88 (d, J = 17.7 Hz, 1 H), 5.50 (d, J = 11.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 158.7, 141.4, 129.6, 125.7, 124.6, 123.2, 118.3, 116.1.
MS (EI): m/z (%) = 165 (M+, 61), 135 (37), 91 (73), 89 (29), 85 (26), 83 (28), 77 (25), 65 (50), 57 (33), 55 (24), 43 (41), 40 (100), 39 (30).
HRMS (EI): m/z [M]+ calcd for C8H7O3N: 165.0426; found: 165.0410.
Anal. Calcd for C8H7O3N (165.15): C, 58.18; H, 4.27; N, 8.48. Found: C, 57.71; H, 4.26; N, 8.48.
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1-(Allyloxy)-4-nitro-2-vinylbenzene (5i)[ 60 ]
Following the general procedure for the O-allylation of phenols 9 using styrene 11i (645 mg, 3.9 mmol) gave 5i (704 mg, 88%) as a yellow liquid.
IR (neat): 3088 w), 2930 (w), 1582 (m), 1512 (s), 1339 (s), 1270 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 8.35 (d, J = 2.8 Hz, 1 H), 8.11 (dd, J = 9.1, 2.8 Hz, 1 H), 7.03 (dd, J = 17.7, 11.2 Hz, 1 H), 6.91 (d, J = 9.1 Hz, 1 H), 6.07 (ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.88 (dd, J = 17.7, 0.9 Hz, 1 H), 5.44 (dddd, J = 17.3, 1.6, 1.5, 1.5 Hz, 1 H), 5.43 (dd, J = 11.1, 0.8 Hz, 1 H), 5.36 (dddd, J = 10.5, 1.3, 1.3, 1.3 Hz, 1 H), 4.68 (ddd, J = 5.1, 1.4, 1.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 160.2, 141.5, 131.9, 129.8, 127.7, 124.5, 122.1, 118.5, 117.2, 111.5, 69.6.
MS (EI): m/z (%) = 205 (M+, 9), 177 (8); 164 (20), 118 (36), 89 (23), 63 (15), 41 (100).
HRMS (EI): m/z [M]+ calcd for C11H11NO3: 205.0733; found: 205.0749.
Anal. Calcd for C11H11NO3 (205.21): C, 64.38; H, 5.40; N, 6.83. Found: C, 64.10; H, 5.30; N, 7.55.
#
4-(Allyloxy)-3-vinylbenzaldehyde (5k)
Diene 5d (2.39 g, 10.0 mmol) was dissolved in THF (100 mL) and cooled to –90 °C. At this temperature 1.6 M n-BuLi in hexane (4.64 mL, 11.6 mmol) was added via syringe pump over a period of 1.5 h. After complete addition of n-BuLi, the soln was stirred for an additional 30 min at this temperature. Then DMF (10 mL, 144 mmol) was added over a period of 20 min, the soln was allowed to warm to r.t., and stirring was continued for 12 h. Sat. NH4Cl soln (40 mL) and MTBE (130 mL) were added, the organic layer was separated and washed with half-sat. soln NH4Cl (3 × 30 mL). The organic layer was dried (MgSO4), filtered, and all volatiles were removed in vacuo. The residue was purified by column chromatography to give aldehyde 5k (1.49 g, 79%) as a colorless liquid.
IR (neat): 3087 (w), 3024 (w), 2821 (w), 2729 (w), 1686 (s), 1625 (m), 1593 (s), 1490 (m), 1251 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 9.89 (s, 1 H), 8.00 (m, 1 H), 7.74 (ddd, J = 8.6, 1.8, 1.8 Hz, 1 H), 7.06 (dd, J = 17.7, 11.2 Hz, 1 H), 6.95 (d, J = 8.5 Hz, 1 H), 6.06 (m, 1 H), 5.85 (d, J = 17.7 Hz, 1 H), 5.43 (m, 1 H), 5.37 (m, 1 H), 5.33 (m, 1 H), 4.64 (br d, J = 5.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 190.8, 160.4, 132.3, 131.1, 130.5, 129.8, 128.1, 127.7, 118.0, 116.1, 111.9, 69.2.
MS (EI): m/z (%) = 188 (M+, 64), 187 (14), 173 (15), 160 (28), 159 (55), 158 (30), 147 (54), 145 (22), 141 (19), 131 (17), 119 (29), 91 (100), 89 (17), 65 (23), 41 (60).
HRMS (EI): m/z [M]+ calcd for C12H12O2: 188.0832; found: 188.0831.
Anal. Calcd for C12H12O2 (188.22): C, 76.57; H, 6.43. Found: C, 76.27; H, 6.48.
#
1-(Allyloxy)-2,4-divinylbenzene (5j)
Following the general procedure for the Wittig olefination of aldehydes or ketones 10 using 5k (564 mg, 3.0 mmol) gave 5j (5.58 g, >98%) as a colorless liquid.
IR (neat): 3085 (m), 3020 (m), 2923 (m), 2854 (m), 1628 (m), 1600 (m), 1491 (s), 1422 (m), 1246 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.52 (m, 1 H), 7.25 (dd, J = 8.5, 1.9 Hz, 1 H), 7.07 (dd, J = 17.7, 11.1 Hz, 1 H), 6.78 (d, J = 8.5 Hz, 1 H), 6.65 (dd, J = 17.6, 10.9 Hz, 1 H), 6.04 (m, 1 H), 5.77 (m, 1 H), 5.63 (m, 1 H), 5.40 (m, 1 H), 5.31–5.20 (2 H), 5.14 (m, 1 H), 4.54 (ddd, J = 5.1, 1.6, 1.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 155.6, 136.3, 133.3, 131.6, 130.6, 127.1, 126.6, 124.5, 117.3, 114.6, 112.4, 111.9, 69.3.
MS (EI): m/z (%) = 186 (M+, 38), 145 (19), 117 (73), 116 (19), 115 (79), 91 (29), 85 (67), 83 (100), 47 (42), 41 (30), 39 (35).
HRMS (EI): m/z [M]+ calcd for C3H14O: 186.1039; found: 186.1030.
Anal. Calcd for C13H14O (186.25): C, 83.83; H, 7.58. Found: C, 83.79; H, 7.80.
#
#
Acknowledgment
Generous financial support of this work by the Deutsche Forschungsgemeinschaft (DFG-grant Schm 1095/6) is gratefully acknowledged.
Supporting Information
- for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.
- Supporting Information
-
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