Synlett 2018; 29(06): 785-792
DOI: 10.1055/s-0036-1591528
letter
© Georg Thieme Verlag Stuttgart · New York

An Atom-Economic and Stereospecific Access to Trisubstituted Olefins through Enyne Cross Metathesis Followed by 1,4-Hydrogenation

Friederike Ratsch
University of Cologne, Department of Chemistry, Greinstraße 4, 50939 Köln, Germany   Email: schmalz@uni-koeln.de
,
University of Cologne, Department of Chemistry, Greinstraße 4, 50939 Köln, Germany   Email: schmalz@uni-koeln.de
› Author Affiliations
Further Information

Publication History

Received: 24 October 2017

Accepted after revision: 10 December 2017

Publication Date:
15 January 2018 (online)

Abstract

The combination of intermolecular enyne cross metathesis and subsequent 1,4-hydrogenation opens a stereocontrolled and atom-economic access to trisubstituted olefins. By investigating different combinations of functionalized alkyne and alkene substrates, we found that the outcome (yield, E/Z ratio) of the Grubbs II-catalyzed enyne cross-metathesis step depends on the substrate’s structure, the amount of the alkene (used in excess), and the (optional) presence of ethylene. In any case, the 1,4-hydrogenation, catalyzed by 1,2-di­methoxybenzene-Cr(CO)3, proceeds stereospecifically to yield exclusively the E-products from both the E- and Z-1,3-diene intermediates obtained by metathesis. A rather broad scope and functional group compatibility of the method is demonstrated by means of 15 examples.

Supporting Information

 
  • References and Notes

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  • 25 Detailed experimental procedures and characterization data are given in the Supporting Information. General Procedure for Enyne Metathesis A Schlenk flask was filled under argon with 0.1 equiv of catalyst 6, cooled to 0 °C and flushed with ethylene. Then, dry CH2Cl2 (2.0 ml/mmol alkyne), 1.0 equiv of the alkyne (1) and 10 equiv of the alkene 2 were added, and the reaction mixture was stirred at r.t. for 24–72 h. The catalyst was removed by stirring the reaction mixture with active charcoal. The suspension was then filtered over silica, and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on SiO2/AgNO3 (cHex/EtOAc) to afford the diene 3 as colorless oil. Analytical Data of Selected Dienes Compound 3a: 1H NMR (500 MHz, CDCl3): δ = 7.38–7.30 (m, 5 H,), 6.04 (d, 3 J H,H = 15.8 Hz, 1 H), 5.72 (dt, 3 J H,H = 15.8 Hz, 6.9 Hz, 1 H), 5.12 (s, 2 H), 4.90 (s, 1 H), 4.84 (s, 1 H), 2.56 (m, 4 H), 2.11–2.06 (m, 2 H), 1.41–1.35 (m, 2 H), 1.32–1.25 (m, 6 H), 0.88 (t, 3 J H,H = 6.9 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 173.2, 144.6, 136.1, 131.5), 130.9, 128.7, 128.3, 113.6, 66.4, 33.3, 33.0, 31.8, 29.4, 29.0, 27.4, 22.7, 14.2 ppm. HRMS (ESI): m/z calcd [M+H]+ for C20H28O2: 301.21621; found: 301.21666. Compound 3d: 1H NMR (500 MHz, CDCl3): δ = 8.08–8.06, 7.58–7.54 (m, 1 H), 7.46–7.43 (m, 2 H), 6.12 (d, 3 J H,H = 16.0 Hz, 1 H), 5.81 (dt, 3 J H,H = 16.0 Hz, 6.9 Hz, 1 H), 5.22 (s, 1 H), 5.14 (s, 1 H), 4.99 (s, 2 H), 2.14–2.10 (m, 2 H), 1.42–1.36 (m, 2 H), 1.35–1.30 (m, 2 H), 0.89 (t, 3 J H,H = 7.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.4, 140.7, 133.1, 132.1, 130.3, 129.8, 129.3, 128.5, 115.4, 64.8, 32.8, 31.5, 22.3, 14.0 ppm. HRMS (ESI): m/z calcd [M + H]+ for C16H20O2: 245.15361; found: 245.15396. Compound 3i: 1H NMR (500 MHz, CDCl3): δ = 7.26–7.24 (m, 2 H), 6.88–6.85 (m, 2 H), 6.28 (d, 3 J H,H = 15.6 Hz, 1 H), 5.67 (dt, 3 J H,H = 15.6 Hz, 7.0 Hz, 1 H), 5.11 (d, 4JH,H = 1,4 Hz, 1 H), 5.01 (d, 3 J H,H = 1.8 Hz, 1 H), 3.81 (s, 3 H), 2.14–2.10 (m, 2 H), 1.40–1.28 (m, 4 H), 0.89 (t,3 J H,H = 7.2 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 159.1, 147.7, 134.5, 133.3, 131.6, 129.4, 113.7, 113.6, 55.4, 32.7, 31.6, 22.4, 14.1 ppm. General Procedure for 1,4-Hydrogenation Under argon atmosphere, 1.00 equiv of the diene were dissolved in dry THF (4.0 ml/mmol diene) in a glass reaction vial. Then 0.05 equiv of the (arene)Cr(CO)3 catalyst were added, and the vial was placed in a Parr autoclave. After sealing the autoclave and purging it three times with hydrogen (30 bar), the hydrogen pressure was set to 41–59 bar, and the temperature raised to 120 °C for 15–20 h (overnight). After cooling to r.t., the solvent was evaporated under reduced pressure, and the crude product was dissolved in EtOH (4.0 ml/mmol diene). To oxidize the remaining catalyst, 1.0 equiv of anhydrous FeCl3 were added, and nitrogen was bubbled through the mixture for 30 min. Then, water was added, and the mixture was extracted 3 times with petrol ether or cyclohexane. The combined organic layers were dried over Na2SO4 under reduced pressure, and the crude product was purified by column chromatography on silica (cHex/EtOAc). Analytical Data of Selected Trisubstituted Olefins Compound 4a: 1H NMR (300 MHz, CDCl3): δ = 7.37–7.30 (m, 5 H), 5.16–5.13 (m, 1 H), 5.10 (s, 2 H), 2.48–2.45 (m, 2 H), 2.33–2.31 (m, 2 H), 1.96–1.93 (m, 2 H), 1.59 (s, 3 H), 1.32–1.23 (m, 10 H), 0.88 (t, 3 J H,H = 7.0 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 173.4, 136.2, 133.1, 128.7, 128.3, 128.3, 125.9, 66.2, 34.8, 33.4, 32.0, 29.9, 29.4, 29.4, 28.0, 22.8, 16.0, 14.3 ppm. HRMS (EI): m/z calcd [M]+ for C20H30O2: 302.2245; found: 302.232. Compound 4d: 1H NMR (500 MHz, CDCl3): δ = 8.07–8.05 (m, 2 H), 7.57–7.53 (m, 1 H), 7.45–7.42 (m, 2 H), 5.58–5.55 (m, 1 H), 4.71 (s, 2 H), 2.09–2.04 (m, 2 H), 1.74 (s, 3 H), 1.41–1.35 (m, 2 H), 1.34–1.27 (m, 4 H), 0.89 (t, 3 J H,H = 7.0 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.6, 133.0, 130.6, 130.3, 130.0, 129.7, 128.5, 70.9, 31.7, 29.1, 27.9, 22.7, 14.2, 14.2 ppm. HRMS (ESI): m/z calcd [M + Na]+ for C16H22O2: 269.15120; found: 269.15154. Compound 4i: 1H NMR (500 MHz, CDCl3): δ = 7.33–7.30 (m, 2 H), 6.86–6.83 (m, 2 H), 5.72–5.69 (m, 1 H), 3.80 (s, 3 H), 2.17 (q, 3 J H,H = 7.3 Hz, 2 H), 2.00 (s, 3 H), 1.47–1.41 (m, 2 H), 1.34–1.31 (m, 4 H), 0.90 (t, 3 J H,H = 6.9 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.5, 136.8, 133.9, 127.4, 126.7, 113.6, 55.4, 31.8, 29.6, 28.9, 22.8, 15.9, 14.3 ppm. Compound 4k: 1H NMR (300 MHz, CDCl3): δ = 8.06–8.05 (m, 2 H), 7.57–7.54 (m, 1 H), 7.46–7.43 (m, 2 H), 5.54–5.51 (m, 1 H), 4.71 (s, 2 H), 2.44 (t, 3 J H,H = 7.4 Hz, 2 H), 2.14 (s, 3 H), 2.09 (‘q’, 3 J H,H = 7.6 Hz, 2 H), 1.73 (s, 3 H), 1.68 (‘p’, 3JH,H = 7.4 Hz) ppm. 13C NMR (75 MHz, CDCl3): δ = 208.9, 166.5, 133.0, 131.2, 130.5, 129.7, 128.7, 128.5, 70.5, 43.1, 30.1, 27.1, 23.4, 14.2 ppm. Compound 4n: 1H NMR (300 MHz, CDCl3): δ = 8.07–8.04 (m, 2 H), 7.59–7.54 (m, 1 H), 7.47–7.42 (m, 2 H), 5.53 (t, 3 J H,H = 7.2 Hz, 1 H), 4.71 (s, 2 H), 2.35 (t, 3 J H,H = 6.9 Hz, 2 H), 2.13 (‘q’, 3JH,H = 7.2 Hz, 2 H), 1.74 (s, 3 H), 1.71–1.64 (m, 2 H), 1.61–1.51 (m, 2 H) ppm.13C NMR (75 MHz, CDCl3): δ = 166.5, 133.1, 131.3, 130.5, 129.7, 128.5, 128.3, 119.8, 70.5, 28.4, 27.0, 25.1, 17.2, 14.2 ppm. HRMS (EI): m/z calcd [M]+ for C16H19NO2: 257.1416; found: 257.143.