Coenzyme models. Part 52. Diastereo-differentiating hydrogen transfer in 5-deazaflavin oxidation of alcohols and amines

Abstract

5-Deuteriated 5-deazaflavinophanes (dFI(n)^D) were synthesized in which N-3 in the isoalloxazine group and O-2′ in the 10-(2-hydroxyphenyl) group were linked by a –(CH₂)_n– chain (n= 8 and 10). ¹H NMR studies established that NaBH₄ reduction of dFI(8)^D to the reduced form dFl_red(8)^D, in which ring inversion is inhibited because of a short (CH₂)₈ strap, gives an axial C-5 proton (H_ax). This indicates that hydrogen is exclusively incorporated into the axial C-5 position. In contrast, NaBH₄ reduction of dFI(10)^D to dFl_red(10)^D, in which ring inversion is allowed because of a long (CH₂)₁₀ strap, gave an axial and an equatorial proton (H_ax and H_eq) in the ratio 1 : 1. This indicates that hydrogen is primarily incorporated into the axial C-5 position but is rapidly exchanged through ring inversion. Oxidation of alcohols and amines by dFI(n)^D gave ¹H NMR spectra similar to those obtained after NaBH₄ reduction. Therefore we conclude that hydrogen from these substrates is also transferred to the axial C-5 position. The ‘axial preference’, which is generally observed for 5-deazaflavin-mediated redox reactions, was rationalized in terms of the stereoelectronic effect.