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Synlett 2011(19): 2867-2871  
DOI: 10.1055/s-0031-1289855
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile Synthetic Route for the Preparation of 4-Substituted 6-Methyl-2-pyrone Derivatives via Organozinc Reagents

Reuben D. Riekea, Seung-Hoi Kim*b
a Rieke Metals, Inc., 1001 Kingbird Rd., Lincoln NE 68521, USA
b Department of Chemistry, Dankook University, 29 Anseo, Cheonan 330-714, Korea
Fax: +82(41)5597860; e-Mail: kimsemail@dankook.ac.kr;
Further Information

Publication History

Received 30 August 2011
Publication Date:
09 November 2011 (online)

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Abstract

A novel synthetic pathway for the preparation of 4-substituted 2-pyrone derivatives has been developed. It consists of two different methods; the first represents the Negishi coupling reaction utilizing easily accessible organozinc reagents. More significantly, the other is a new method utilizing a new organozinc reagent, 4-pyronylzinc bromide, which is easily prepared by highly active zinc under mild conditions.

Key words

organozinc - cross-coupling reaction - 4-substituted ­pyrone

    References and Notes

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6

Preparation of 6-Methyl-4-pyronylzinc Bromide (I): Into an oven-dried 25-mL round-bottomed flask equipped with a stir bar was added active zinc (Zn*, 1.25 g, 19 mmol). 4-Bromo-6-methyl-2-pyrone (2.40g, 12.7 mmol) dissolved in THF (5.0 mL) was then cannulated neat into the flask at r.t. The resulting mixture was stirred at r.t. for 30 min. The whole mixture was allowed to settle down and then the supernatant was used for the subsequent coupling reactions.

7

A Representative Procedure of Pd-Catalyzed Coupling Reaction: Into a 25-mL round-bottomed flask was added Pd(PPh3)4 (0.06g, 1 mol%) under an argon atmosphere. Next, I (0.5 M in THF, 10 mL, 5.0 mmol) was added via a syringe, and then benzoyl chloride (0.56 g, 4.0 mmol) was added slowly into the flask at r.t. The resulting mixture was stirred at r.t. for 30 min. The reaction was quenched with sat. NH4Cl solution and the mixture was then extracted with Et2O (3 × 10 mL). It was washed with sat. NaHCO3, Na2S2O3 solution and brine, then dried over anhyd MgSO4. Purification by column chromatography on silica gel (20% EtOAc-80% heptane) afforded 2a (0.80 g) as a yellow solid in 94% isolated yield. GC-MS (EI): m/z (%) = 214 (50) [M+], 186 (62), 105 (100), 77 (99), 43 (75).

8

A Representative Procedure for Cu-Catalyzed Coupling Reaction: Into a 25-mL round-bottomed flask were added CuI (0.09 g, 10 mol%) and LiCl (0.04 g, 20 mol%) under an argon atmosphere. Next, I (0.5 M in THF, 10 mL, 5.0 mmol) was added via a syringe, and then cyclopropanecarbonyl chloride (0.41 g, 4.0 mmol) was added slowly into the flask at r.t. The resulting mixture was stirred at 0 ˚C for 60 min. The reaction was quenched with sat. NH4Cl solution and the mixture was then extracted with Et2O (3 × 10 mL) and washed with sat. NaHCO3, 7% NH4OH, sat. Na2S2O3 solution and brine, and then dried over anhyd MgSO4. Purification by column chromatography on silica gel (20% EtOAc-80% heptane) afforded 3a (0.65 g) as a yellow solid in 91% isolated yield. GC-MS (EI): m/z (%) = 178 (25) [M+], 150 (50), 109 (82), 69 (75), 43 (100).

9

pK a values; range between 15-20 for phenols, 20-30 for anilines, source from http://www.chem.wisc.edu/areas/reich/pkatable/index.htm.