Efficient Olefin Isomerization-Ring-Closing Metathesis Reaction in Sterically Hindered Systems: Study on Simultaneous Use of the Grubbs Metathesis and Ruthenium Hydride Isomerization Catalysts

Abstract

Efficient double bond isomerization-ring-closing metathesis reaction is observed when sterically congested 1,9-dienes are treated with Grubbs ruthenium catalysts; simultaneous use of Grubbs catalyst and RuClH(CO)(PPh₃)₃ facilitate isomerization-metathesis reactions.

Key words

annulations - fused-ring systems - metathesis - ruthenium hydrides - tandem reactions

References

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• 1a Grubbs RH. Chang S. Tetrahedron  1998,  54:  4413 
• 1b Fürstner A. Angew. Chem. Int. Ed.  2000,  39:  3013 
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• 17b

  Typical Procedure for S -( tert -Butyl) (2 R* )-2-[(1 R* ,2 R* )-2-Allyl-2-methyl-3-oxocyclopentyl]hex-5-enethioate (15). To a solution of 1-(tert-butylthio)-1-trimethylsilyloxyhexa-1,5-diene (1.551 g, 6 mmol, 1.2 equiv) in CH₂Cl₂ (45 mL), TMSOTf (45 µL, 0.3 mmol, 5 mol%), 2-methylcyclopent-2-en-1-one (0.5 mL, 5 mmol) were consecutively added at
  -78 °C. The mixture was stirred for 3 h and then the reaction was quenched with 2-pyridinemethanol (36 µL, 0.37 mmol, 7.5 mol%). After 15 min, hexane (90 mL) was added, the bright yellow solution was filtered through silica gel (10 g, deactivated with 2% Et₃N in hexane), and the solvent was evaporated to give tert-butyl (2R*)-2-{(1R*)-2-methyl-3-[1,1,1-(trimethylsilyl)oxy]-2-cyclopentenyl}-5-hexene-thioate (silyl enol ether, oil, 1.806 g, 98%). To a solution of Pd₂ (dba)₃ (137 mg, 0.15 mmol, 3 mol%) and dppe (356 mg, 0.92 mmol, 18 mol%) in THF (24 mL), the crude silyl enol ether in THF (12 mL) and allyl methyl carbonate (1.138 g, 9.8 mmol) were added. The mixture was heated under refluxed for 6 h, cooled and the solvent was evaporated. The residue was purified by chromatography on silica gel (3% EtOAc-hexanes) to give 15 (yellow oil, 1.58 g, 68%):
  ¹H NMR (200 MHz): δ = 5.90-5.50 (m, 2 H), 5.10-4.92 (m, 4 H), 2.70-2.25 (m, 4 H), 2.20-1.85 (m, 5 H), 1.80-1.55 (m, 3 H), 1.49 (s, 9 H), 1.01 (s, 3 H). ¹³C NMR (50 MHz):
  δ = 221.9, 202.9, 137.8, 133.8, 118.7, 115.3, 54.0, 52.3, 48.7, 43.1, 39.8, 37.5, 30.8, 29.6, 23.4, 18.7. HRMS: m/z calcd for C₁₉H₃₀O₂S: 322.1967; found: 322.1970.

13

Typical Procedures.
Methyl (3a R* ,4 R* ,8a R* )-8a-Methyl-1-oxo-1,2,3,3a,4,5,8,8a-octahydroazulene-4-carboxylate (10)
To a solution of 6 (3.9 mg, 0.0048 mmol, 3% mol) in benzene (10 mL), diene 8 (42 mg, 0.159 mmol) in benzene (10 mL) was added and the mixture was heated under reflux for 72 h. Then solvent was evaporated, and the residue was purified by chromatography on silica gel (5% EtOAc-hexanes) to give 10 (oil, 20 mg, 56%): HPLC. t _R = 6.42 min, 94% purity (RI detector, MeOH-H₂O = 6:4). ¹H NMR (500 MHz): δ = 6.08-5.97 (m, 1 H), 5.82-5.71 (m, 1 H), 3.67 (s, 3 H), 2.90-2.84 (m, 1 H), 2.72-2.63 (m, 1 H), 2.50-2.33 (m, 3 H), 2.25-2.06 (m, 3 H), 2.04-1.97 (m, 1 H), 1.96-1.87 (m, 1 H), 0.76 (s, 3 H). ¹³C NMR (50 MHz): δ = 221.0, 174.2, 131.5, 127.7, 53.5, 51.5, 49.4, 42.9, 35.5, 35.2, 30.4, 24.2, 14.9. HRMS: m/z calcd for C₁₃H₁₈O₃: 222.1256; found: 222.1262.
S -( tert -Butyl) (3a R* ,4 R* ,8a R* )-7,8a-Dimethyl-1-oxo-1,2,3,3a,4,5,8,8a-octahydroazulene-4-carbothioate (16).
A flame-dried flask equipped with a condenser was charged with 5 (8.8 mg, 0.010 mmol, 5 mol%), 7 (9.9 mg, 0.010 mmol, 5 mol%) and benzene (10 mL). The mixture was briefly stirred to dissolve the catalysts and then ester 12 (69.9 mg, 0.208 mmol) in benzene (10 mL) was added. The solution was heated under reflux for 6 h. The solvent was evaporated and the residue was purified by chromatography on silica gel (5% EtOAc-hexanes) to give 16 (61.1 mg, 100%). ¹H NMR (200 MHz): δ = 5.69 (br t, J = 6.0 Hz, 1 H), 2.95-2.85 (m, 1 H), 2.65-1.90 (m, 9 H), 1.78 (s, 3 H), 1.44 (s, 9 H), 0.86 (s, 3 H). ¹³C NMR (50 MHz): δ = 222.8, 201.5, 136.9, 123.4, 53.2, 52.8, 49.0, 48.0, 40.2, 35.4, 30.0, 29.7, 27.4, 24.0, 15.7. HRMS: m/z calcd for C₁₇H₂₆O₂S: 294.1654; found: 294.1651.

15

The respective β,γ-unsaturated thioester was isolated in ca. 5% yield.
Typical Procedure for S -( tert -Butyl) (2 R* )-2-[(1 R* ,2 R* )-2-Methyl-2-(2-methylprop-2-enyl)-3-oxocyclo-pentyl]hex-4-enethioate (20).
To a solution of 7 (5.1 mg, 0.054 mmol, 1% mol) in benzene (4 mL), 12 (180.6 mg, 0.54 mmol) in benzene (4 mL) was added and the mixture was heated under reflux for 10 min (GC analysis indicated consumption of the substrate). The solvent was evaporated and the residue was purified by chromatography on silica gel (5% EtOAc-hexanes) to give 20 (157.1 mg, 87%). R _f = 0.64 (10% EtOAc-hexanes). GC: 15.5 and 15.9 (E:Z = 2.6:1, 150-250 °C, 150 °C, 1 min, 10 °C/min). ¹H NMR (200 MHz): δ = 5.64-5.26 (m, 2 H), 4.85 (br s, 1 H), 4.68 (br s, 1 H), 2.76-1.96 (m, 10 H), 1.63 (d, J = 5.2 Hz, 3 H), 1.58 (s, 3 H), 1.45 (s, 9 H), 1.03, 1.02 (s, 3 H). ¹³C NMR (50 MHz): δ = 222.6, 202.4, 141.5, 127.8, 126.9, 126.2, 126.0, 115.2, 55.1, 54.7, 51.6, 48.5, 43.7, 42.5, 37.5, 34.8, 29.7, 28.9, 24.6, 23.4, 23.3, 20.2, 17.8. HRMS: m/z calcd for C₃₂H₄₈O₆Na: 336.2123; found: 336.2126.