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Synlett 2007(6): 0974-0976  
DOI: 10.1055/s-2007-973861
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Versatile Synthesis of Esters from Grignard Reagents and Chloroformates

Daniela Bottalico, Vito Fiandanese, Giuseppe Marchese, Angela Punzi*
Dipartimento di Chimica, Università di Bari, Via Orabona 4, 70126 Bari, Italy
Fax: +39(080)5442075; e-Mail: punzi@chimica.uniba.it;
Further Information

Publication History

Received 11 December 2006
Publication Date:
26 March 2007 (online)

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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.

Key words

organometallic reagents - cross-coupling - chemoselectivity - esters

    References and Notes

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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): νmax = 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.