Chiral effects on the 13C resonances of α-tocopherol and related compounds. A novel illustration of Newman's "rule of six"
Resolve DOI: https://doi.org/10.1021/jo00264a012
Search for: Brownstein, S.1; Search for: Burton, G.W.1; Search for: Hughes, L.1; Search for: Ingold, K. U.1
National Research Council of Canada
alpha tocopherol; isophytol; phytol; tocopherol derivative; carbon nuclear magnetic resonance; drug structure
The 100-MHz 13C NMR spectrum of (2R,4′R,8′R)-α-tocopherol (natural vitamin E) has been completely assigned with the aid of a number of selectively deuteriated (2R,4′R,8′R)-α-tocopherols. The 13C NMR spectrum of (2RS,4′RS,8′RS)-α-tocopherol (all-racemic, synthetic vitamin E) has also been measured. Many of the individual carbons in this all-racemic mixture of eight α-tocopherol stereoisomers give more than one resonance with eight of the carbons (2-CH3, 2′, 3′, 4′, 4′-CH3, 5′, 8′, and 9′) giving the maximum number of four resonances from each of the four enantiomeric pairs; these resonances have also been assigned. The structurally related 5′-hydroxy-2-(4′,8′,12′-trimethyltridecyl)-2,4,6,7- tetramethyl-2,3-dihydrobenzofuran (HTDBF) has been synthesized for the first time in the 2R,4′R,8′R and 2S,4′R,8′R configurations and their 13C resonances have been assigned. In its all-racemic form this compound also shows up to four resonances from a single carbon. Related observations have been made with phytol and isophytol. A careful examination of these chirally induced chemical shift differences for the individual carbon atoms, Δ, reveals a bond-alternation effect with maxima at a separation of one, three, and five bonds from the closest chiral center and with the maximum at a five-bond separation being greater than that at a three-bond separation. For example, the total Δ, ∑Δ, averaged over the number of carbon aroms, n, which are separated from the nearest chiral center by the same number of bonds has been conservatively calculated for α-tocopherol to be 54, 106, 43, 66, 40, and 75 ppb at separations from the closest chiral center of zero, one, two, three, four, and five bonds, respectively. For HTDBF the corresponding ∑Δ/n values are 45, 67, 12, 0, 0, and 20 ppb. We attribute these remarkable long-range (five-bond) effects to differences in 1,6 nonbonded repulsions for different enantiomeric pairs and consider that it provides direct evidence for the operation of Newman's classic "rule of six".
Journal of Organic Chemistry 54, no. 3 (1989): 560–569.
99130d7d-24d6-4f1b-96e0-1daa90646049