Dehydroxymethylation: an unusual reverse reaction of nucleophilic addition to formaldehyde

An unusual dehydroxymethylation has been observed in an acyclic primary alcoholic system. The relief of steric congestion is considered as the primary driving force in this reaction. 2006 Elsevier Ltd. All rights reserved. The nucleophilic additions of carbon nucleophiles to aldehydes or ketones are highly favourable processes. Nucleophilic addition of carbon anion to a carbonyl group is normally exothermic. This is attributed to the high reactivity of carbon anion. Moreover, thermodynamically stable products are generated in this reaction. As a result, the reverse process, b-cleavage of alkoxy anion, is rare. The b-cleavage of alkoxy anion becomes a facile process mainly in a ring-fused system, in which the hydroxyl group is positioned at a bridgehead. The driving force for this process is obviously the relief of the fused-ring strain. This type of b-cleavage has been successfully utilized in the synthesis of mediumto largesized rings. In this letter, we report an unu ual alkoxy anion b-cleavage in a non-cyclic system. In connection with our study on stereoselective [2,3] r rearrangement of sulfur ylides generated from metal carbene and allyl sulfides, a series of tertiary sulfides 1a–j was prepared. Oxidation of the sulfides 1a with mCPBA gave sulfone 2a. When sulfone 2a was treated with sodium hydride, a new product was isolated. Inspection of the spectral data suggested that the structure of this product was 3a, in which the hydroxymethyl group was lost (Scheme 1). The structure of 3a was further confirmed by X-ray crystallography analysis, as shown in Figure 1. This dehydroxymethylation was found to be general for sulfones 2b–j. As shown in Table 1, the oxidation of 1b–j with mCPBA gave sulfones 2b–j in high yields, subsequent treatment of 2b–j with sodium hydride in THF afforded dehydroxymethylation products in moderate to good yields. The substituent on the Ar group was found to have no influence on the reaction. As shown by entries 2 and 7, both the electron-withdrawing NO2 group and electron-donating OMe group gave dehydroxymethylation products in similar yields. The extrusion of hydroxymethyl group from 2a is surprising. A mechanism is proposed for this process. Upon treatment with sodium hydride, the alkoxy anion A is first generated and then followed by the b-cleavage of C–C bond to afford 3a after protonation. The carbon O + HCHO Ar OH S Ar' 1a, Ar = 4-BrC6H4, Ar' = 2-ClC6H4 1b, Ar = 3,4-Cl2C6H3, Ar' = 2-ClC6H4 1c, Ar = 4-NO2C6H4, Ar' = 2-ClC6H4 1d, Ar = 3-MeC6H4, Ar' = 2-ClC6H4 1e, Ar = C6H5, Ar' = 2-ClC6H4 1f, Ar = 4-ClC6H4, Ar' = C6H5 1g, Ar = 3-ClC6H4, Ar' = C6H5 1h, Ar = 4-MeOC6H4, Ar' = C6H5 1i, Ar = 1j, Ar = C6H5, Ar' = C6H5 S , Ar' = C6H5 0040-4039/$ see front matter 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.09.017