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Synlett 2010(17): 2625-2627  
DOI: 10.1055/s-0030-1258581
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Convenient Procedure for the Indium-Mediated Hydroxymethylation of Active Bromo Compounds: Transformation of Ketones into α-Hydroxymethyl Nitroalkanes

Raquel G. Soengas*a, Amalia M. Estévezb
a Departmento de Química Fundamental, Universidad de A Coruña, Campus de A Zapateira, s/n, 15071, A Coruña, Spain
b Departmento de Química Orgánica, Universidad de Santiago de Compostela, Avda. da Ciencias, s/n, 15782, Santiago de Compostela, Spain
Fax: +34(981)167065; e-Mail: rsoengas@udc.es;
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Publication History

Received 6 July 2010
Publication Date:
23 September 2010 (online)

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Abstract

A very simple, safe and powerful method for the hydroxymethylation of 2-bromoesters and lactones under anhydrous conditions that avoids the use of gaseous formaldehyde is described. Moreover, under these conditions, bromonitroalkanes were converted into the corresponding α-monohydroxymethylated nitroalkanes, which are precursors of the corresponding α-amino acids. Considering the easy transformation of ketones into bromonitroalkanes, this represents a method for the formal synthesis of α-amino acids from ketones.

Key words

hydroxymethylation - indium - esters - nitroalkanes - amino acids

6

General Procedure: To a suspension of indium powder (0.5 mmol) in THF (1 mL), the 2-bromocompound (0.75 equiv) was added and the mixture was sonicated for 20 min. Paraformaldehyde (0.5 mmol) was then added and sonication was continued for a further 4 h. The reaction mixture was quenched with sat. aq NaHCO3 (10 mL) and extracted with Et2O (3 × 25 mL). The combined organic layers were dried over MgSO4, filtered and the solvent was evaporated in vacuo to obtain pure hydroxymethylated compounds.