Solvent-Free Synthesis of 2-Pyrones from Alkynes and Carbon Dioxide Catalyzed by Ni(1,5-cyclooctadiene)₂/Trialkylphosphine Catalysts

Abstract

Solvent-free, efficient, and mild 2-pyrone synthesis by the cycloaddition of alkynes with CO₂ has been achieved under compressed CO₂ with a Ni(cod)₂/P(C₄H₉)₃ or Ni(cod)₂/P(C₈H₁₇)₃ catalyst; both high yields (up to 98%) and selectivities (up to 99%) are attained. One attractive aspect of these catalysts is their high efficiency at low CO₂ pressures (4 MPa). The applicability of this reaction to a broad range of alkyne substrates and the ease of handling the phosphine ligands are additional merits of the present new catalytic systems in comparison to the previously reported Ni(cod)₂/P(CH₃)₃ catalyst in supercritical CO₂.

2-pyrone derivatives - alkynes - carbon dioxide - Ni(0) complex - solvent-free

References

1a Inoue Y. Itoh Y. Kazama H. Hashimoto H. Bull. Chem. Soc. Jpn.  1980,  53:  3329 

1b Walther D. Schönberg H. Dinjus E. Sieler J. J. Organomet. Chem.  1987,  334:  377 

1c Tsuda T. Morikawa S. Sumiya R. Saegusa T. J. Org. Chem.  1988,  53:  3140 

1d Louie J. Gibby JE. Farnworth MV. Tekavec TN. J. Am. Chem. Soc.  2002,  124:  15188 

2 For a discussion of the chemistry of 2-pyrone, see: Stauton J. In Comprehensive Organic Chemistry   Vol. 4:  Samnes PG. Pergamon Press; Oxford: 1979.  p.629 

3a Kvita V. Fischer W. Chimia  1992,  46:  457 

3b Kvita V. Fischer W. Chimia  1993,  47:  3 

4 For a synthesized 2-pyrone with anti-HIV activity, see: Vara Prasad JVN. Para KS. Lunney EA. Ortwine DF. Dunbar JB. Ferguson D. Tummino PJ. Hupe D. Tait BD. Domagala JM. Humblet C. Bhat TN. Liu B. Guerin DMA. Baldwin ET. Erickson JW. Sawyer TK. J. Am. Chem. Soc.  1994,  116:  6989 

5 Benign by Design. Alternative Synthetic Design for Pollution Prevention   Vol. 577:  Anastas PT. Farris CA. American Chemical Society; Washington DC: 1994. 

6 Eckert CA. Knutson BL. Debenedetti PG. Nature (London, U.K.)  1996,  383:  313 

7 Chemical Synthesis Using Supercritical Fluids   Jessop PG. Leitner W. Wiley-VCH; Weinheim: 1999. 

8 Reetz MT. Könen W. Strack T. Chimia  1993,  47:  493 

9 It has been suggested that this reaction might occur as a multiphase reaction (i.e. between CO₂ and catalyst both dissolved in liquid 3-hexyne) and not in scCO₂: Dinjus E. COST/Dechema Workshop   Lahnstein Germany: April 1995. 

10 Kreher U. Schebesta S. Walther D. Z. Anorg. Allg. Chem.  1998,  624:  602 

11

Typical procedure for the Ni(0)-catalyzed cycloaddition of alkynes with CO ₂ : All manipulations were carried out under a nitrogen or argon atmosphere. Alkyne 1a (2 mmol), phosphine 3b (0.4 mmol), and o-xylene (40 µL, internal standard for GC analysis) were mixed in a Schlenk tube. Ni(cod)₂ (0.2 mmol) was placed in a stainless steel autoclave containing a magnetic stirring bar, and, to this, was added the above mixture via a dry syringe. CO₂ (ca. 5 MPa) was quickly introduced, and the autoclave was immersed in an oil bath at 120 °C. When the temperature of the reactor reached the desired temperature (typically after about 10 min), more CO₂ was added to achieve the desired pressure of 15 MPa. The time of the second addition of CO₂ was considered to be the start of the reaction. The mixture was allowed to stir for 20 h. Then, the vessel was removed from the oil bath, immersed in an ice bath for ca. 1 h, and allowed to cool to ca. 0 °C. Excess CO₂ was then slowly vented at ca. 0 °C. The remaining organic liquid was diluted with acetone. The GC analysis of the solution indicated the conversion of 1a and the yield of 2a were 100% and 95%, respectively. Acetone was removed by evaporation, and the residue was chromatographed on silica gel (hexanes-EtOAc, 15:1) to give analytically pure 2a in 91% isolated yield. The product was identified by ¹H NMR and GC-MS analyses. The ¹H NMR spectrum was identical to the spectral data reported in ref. 1a.

12

CAUTION: Certain alkynes turn immediately brown when they are mixed with trialkylphosphines and the use of such alkynes does not give desired results. The reason for this is unclear at this time, but we recommend the use of the alkynes that cause no color change.

13

The product yield was determined by GC analysis on the basis of the alkyne 1 employed. Thus, the yield (%) of 2-pyrone 2 = 100 × [(mmol of alkyne component in 2) / (mmol of 1)] = 100 × [(2 × mmol of 2) / (mmol of 1)]; and the yield (%) of alkyne trimer 4 or 5 = 100 × [(mmol of alkyne component in 4 or 5) / (mmol of 1)] = 100 × [(3 × mmol of 4 or 5) / (mmol of 1)].

The selectivity for 2 is defined as the mol% of 2 in all of the reaction products and is calculated from the yields of 2, 4, and 5 by using the above equations. Thus, the selectivity (%) for 2 = 100 × [(mmol of 2) / (mmol of 2 + mmol of 4 + mmol of 5)] = 100 × [(% yield of 2) / 2] / {[(% yield of 2) / 2] + [(% yield of 4) / 3] + [(% yield of 5) / 3]}.

For safety data for P(CH₃)₃, see:

14a Sigma-Aldrich Library of Chemical Safety Data   Vol. 2:  Lenga RE. Sigma-Aldrich Corp.; Milwaukee: 1995.  p.3435C 

14b Sigma-Aldrich Library of Regulatory & Safety Data   Vol. 1:  Lenga RE. Votoupal KL. Sigma-Aldrich Corp.; Milwaukee: 1993.  p.1087E 

15 For safety data for P(C₂H₅)₃, see: Sigma-Aldrich Library of Regulatory & Safety Data   Vol. 1:  Lenga RE. Votoupal KL. Sigma-Aldrich Corp.; Milwaukee: 1993.  p.1087C 

16

Selected data for compound 2c: ¹H NMR (CDCl₃, 270 MHz): δ = 2.36-2.49 (m, 6 H, CH₂), 2.24-2.29 (t, J = 7.3 Hz, 2 H, CH₂), 1.59-1.70 (m, 2 H, CH₂), 1.30-1.45 (m, 14 H, CH₂), 0.91-1.00 (m, 12 H, CH₃). ¹³C NMR (CDCl₃, 67.5 MHz): δ = 163.7 (C=O), 158.1 (C_vinyl), 154.5 (C_vinyl), 123.2 (C_vinyl), 115.4 (C_vinyl), 33.4 (CH₂), 32.1 (CH₂), 31.2 (CH₂), 30.7 (CH₂), 30.1 (CH₂), 29.3 (CH₂), 27.1 (CH₂), 26.6 (CH₂), 23.3 (CH₂), 23.1 (CH₂), 23.0 (CH₂), 22.6 (CH₂), 14.1 (CH₃), 13.93 (CH₃), 13.90 (CH₃), 13.8 (CH₃). HRMS (EI): m/z calcd for C₂₁H₃₆O₂: 320.2715. Found: 320.2729.

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Through careful column chromatography on silica gel (hexanes-EtOAc, 30:1), analytically pure 2d′ could be isolated from the reaction mixture as a colorless oil (15 mg, 8%). ¹H NMR (CDCl₃, 270 MHz): δ = 2.54 (t, J = 7.6 Hz, 2 H, CH₂), 2.53 (t, J = 7.6 Hz, 2 H, CH₂), 2.09 (s, 3 H, CH₃), 1.94 (s, 3 H, CH₃), 1.19 (t, J = 7.6 Hz, 3 H, CH₃), 1.07 (t, J = 7.6 Hz, 3 H, CH₃). ¹³C NMR (CDCl₃, 67.5 MHz): δ = 163.4 (C=O), 157.9 (C_vinyl), 150.8 (C_vinyl), 124.4 (C_vinyl), 110.8 (C_vinyl), 24.6 (CH₂), 20.5 (CH₂), 16.3 (CH₃), 13.0 (CH₃), 12.8 (CH₃), 12.1 (CH₃). ¹H NMR: NOE enhancement (2.8%) between the methyl protons at 1.94 ppm and the methyl protons at 2.09 ppm was observed. HRMS (EI): m/z calcd for C₁₁H₁₆O₂: 180.1146. Found: 180.1144.

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Selected data for compound 2e: ¹H NMR (CDCl₃, 270 MHz): δ = 4.47 (s, 2 H, CH₂O), 4.45 (s, 2 H, CH₂O), 4.37 (s, 2 H, CH₂O), 4.33 (s, 2 H, CH₂O), 3.42 (s, 3 H, CH₃O), 3.41 (s, 3 H, CH₃O), 3.40 (s, 3 H, CH₃O), 3.37 (s, 3 H, CH₃O). ¹³C NMR (CDCl₃, 67.5 MHz): δ = 162.1 (C=O), 158.6 (C_vinyl), 152.1 (C_vinyl), 123.7 (C_vinyl), 115.4 (C_vinyl), 68.6 (CH₂O), 67.0 (CH₂O), 65.6 (CH₂O), 65.1 (CH₂O). HRMS (EI): m/z calcd for C₁₃H₂₀O₆: 272.1260. Found: 272.1257.

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Selected data for compound 5e: ¹H NMR (CDCl₃, 270 MHz): δ = 4.60 (s, 12 H, CH₂O), 3.41 (s, 18 H, CH₃O). MS (EI): m/z (%) = 310 (38) [M⁺ - 32], 295 (100), 265 (42), 233 (30), 203 (23).

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