A New Versatile Synthesis of Esters from Grignard Reagents and Chloroformates

Abstract

Cross-coupling reactions of chloroformates with organocopper reagents, derived from Grignard reagents, cuprous bromide and lithium bromide, provide a rapid and straightforward method for the synthesis of esters.

organometallic reagents - cross-coupling - chemoselectivity - esters

References and Notes

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<A NAME="RG34806ST-1B">1b</A> Smith BM. March J. Advanced Organic Chemistry   5th ed.:  J. Wiley and Sons; Chichester: 2001. 

<A NAME="RG34806ST-2">2</A> Babudri F. Fiandanese V. Marchese G. Punzi A. Tetrahedron Lett.  1995,  36:  7305 ; and references therein

<A NAME="RG34806ST-3">3</A> For a general review on the acylation of organometallic reagents, see: Dieter RK. Tetrahedron  1999,  55:  4177 

<A NAME="RG34806ST-4">4</A> Babudri F. Fiandanese V. Marchese G. Punzi A. Tetrahedron  1996,  52:  13513 

<A NAME="RG34806ST-5">5</A> Babudri F. Fiandanese V. Marchese G. Punzi A. Tetrahedron  1999,  55:  2431 

<A NAME="RG34806ST-6">6</A> Babudri F. Fiandanese V. Marchese G. Punzi A. J. Organomet. Chem.  2004,  689:  326 

<A NAME="RG34806ST-7A">7a</A> Werner T. Barrett AGM. J. Org. Chem.  2006,  71:  4302 

<A NAME="RG34806ST-7B">7b</A> Kashima C. Tsuruoka S. Mizuhara S. Tetrahedron  1998,  54:  14679 

<A NAME="RG34806ST-8">8</A> For an analogous reaction to prepare amides by cross-coupling of carbamoyl chloride with cyano-Gilman cuprates, see: Lemoucheux L. Seitz T. Rouden J. Lasne M.-C. Org. Lett.  2004,  6:  3703 

<A NAME="RG34806ST-9A">9a</A> Boudin A. Cerveau G. Chuit C. Corriu RJP. Reye C. Tetrahedron  1989,  45:  171 

<A NAME="RG34806ST-9B">9b</A> Manfred D, Egon U, and Beate J. inventors; East Ger. Patent DD  273249.  ; Chem. Abstr. 1991, 114, 130219

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For scattered examples using others organometallic reagents, see:

<A NAME="RG34806ST-10A">10a</A> Zhang X. Qiu W. Burton DJ. Tetrahedron Lett.  1999,  40:  2681 

<A NAME="RG34806ST-10B">10b</A> Wiedenau P. Blechert S. Synth. Commun.  1997,  27:  2033 

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<A NAME="RG34806ST-11">11</A> α-Diazocarbonyl compounds have been metalated using Grignard reagents and subsequently allowed to react with chloroformates to produce α-diazocarbonyl-β-ketoesters, see: Cuevas-Yanez E. Muchowski JM. Cruz-Almanza R. Tetrahedron Lett.  2004,  45:  2417 

<A NAME="RG34806ST-12">12</A> Maeda H. Takahashi K. Ohmori H. Tetrahedron  1998,  54:  12233 

<A NAME="RG34806ST-13">13</A>

Typical Experimental Procedure
A THF solution (10 mL) of anhyd LiBr (0.665 g, 7.66 mmol) was added at r.t., under nitrogen, to CuBr (0.549 g, 3.83 mmol). A freshly prepared THF solution of 2,6-dimethyl-phenylmagnesium bromide (4.7 mL, 3.83 mmol) and soon afterwards phenyl chloroformate (0.4 mL, 3.19 mmol) in THF (5 mL) were quickly added to the stirred solution of salts. The mixture was stirred at r.t. for 15 h, quenched with sat. aq NH₄Cl and extracted with EtOAc. The organic extracts were dried over Na₂SO₄ and concentrated under vacuum. The residue was purified by column chromatography (silica gel, PE-EtOAc, 9.8:0.2) leading to phenyl 2,6-dimethylbenzoate 4c (0.707 g, 98% yield). The residual solid was crystallized from hexane giving white crystals of 4c, mp 50-51 °C. IR (KBr): ν_max = 1744, 1600, 1587, 1491, 1466, 1261, 1244, 1182, 1105, 1053, 916, 764, 731, 690 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.48-7.41 (m, 2 H), 7.32-7.22 (m, 4 H), 7.10 (d, J = 7.2 Hz, 2 H), 2.48 (s, 6 H). ¹³C NMR (100.6 MHz, CDCl₃): δ = 168.3, 150.6, 135.2, 132.9, 129.8, 129.6, 127.7, 126.1, 121.5, 19.9. MS: m/z (%) = 226 (<1) [M⁺], 133 (100), 105 (27), 77 (13), 65 (6), 51 (5). The side product phenyl 2,6-dimethylphenyl carbonate (<2%) was identified by the comparison with mass spectral data of an authentic sample independently synthesized: MS: m/z (%) = 242 (99) [M⁺], 198 (62), 197 (25), 183 (97), 165 (49), 155 (18), 148 (44), 121 (27), 120 (100), 105 (32), 103 (20), 94 (20), 92 (48), 91 (72), 79 (40), 78 (22), 77 (73), 51 (25).

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At present, the formation of this side product is not yet clear and is subject to further investigations.