Conversion of Alkyl Halides into Alcohols via Formyloxylation Reaction with DMF Catalyzed by Silver Salts

Abstract

The transformation of alkyl halides into alcohols via a two-step process based on the reaction with DMF catalyzed by Ag(I) salts followed by acid or basic hydrolysis of the intermediate formate ester has been evaluated. The results show that a large variety of primary and some secondary alkyl halides can be transformed efficiently into the corresponding alcohols, making this alkyl halide to alcohol interconversion a valuable alternative to the existing procedures, particularly in molecules with labile functional groups that are generally involved in multistep synthesis.

Key words

alkyl halides - alcohols - catalysis - nucleophilic substitutions - eliminations

References

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19

We have isolated the intermediate imidate salt i (Figure [2] ), formed in the formyloxylation reaction of chlorocarvone 1, by work up of the reaction mixture under anhydrous conditions. This salt has been characterized by ¹H, ¹⁹F, and ¹³C NMR. ¹H NMR (CDCl₃): δ = 8.61 (s, N=CH), 6.80 (m, H-3), 5.44 and 5.28 (2 s, =CH₂), 5.19 (AB system, J = 13 Hz, CH₂O), 3.46 and 3.24 [2 s, N(CH₃)₂], 1.78 (s, CH₃-2). ¹⁹F NMR (CDCl₃, 282 MHz): δ = -152.5. ¹³C NMR (CDCl₃): δ = 198.9 (CO), 167.1 (N=C), 144.5 (C-3), 142.6 (C-2), 137.7 (C-1′), 119.0 (C-2′′), 79.9 (CH₂O), 42.9 (C-6), 41.9 (C-5), 37.7 and 36.5 (Me₂N= ), 30.9 (C-4), 15.6 (CH₃-2).

21

The more reactive bromide 7 can be directly transformed into the corresponding alcohol by treatment with H₂O-CH₃NO₂/AgBF₄. However, the yield of this transformation is significantly lower than that obtained with the DMF-based procedure, due to the formation of substantial amounts of CH₃ (CH₂)₉O(CH₂)₉CH₃ (up to 25%).