Determining the absolute configuration of secondary alcohols by means of a chiral auxiliary and NOESY

The absolute configuration of secondary alcohols can be determined by NOE between the diastereotopic protons of the lactam and the protons of the alcohol moieties in some 1-(alkoxymethyl)-methyl-2-pyrrolidone-5-carboxylate derivatives. Two simple methods based on conformational analysis and 1H NMR data have been developed. The main conformer, in all cases, was established by means of MM, semi-empirical, and ab initio calculations.

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l-Methyl pyroglutamateC9H9NO3[α]D20=+6.2 (c 2.3, EtOH)

1-[(1R′,2S′,5R′)-Menthoxy-methyl]-methyl-(S)-2-pyrrolidone-5-carboxylateC17H29O4N[α]D20=-105.5 (c 0.578, CHCl3)

1-[(1R′,2S′,5R′)-2-Isopropenyl-5-methyl-cyclohexanoxy-methyl]-methyl-(S)-2-pyrrolidone-5-carboxylateC17H27O4N[α]D20=-83.1 (c 4.8, CHCl3)

1-[endo-(1S)-[1′,7′,7′-Trimethylbicyclo[2.2.1]heptan-2′-oxy-methyl]]-methyl-(S)-2-pyrrolidone-5-carboxylateC17H27O4N[α]D20=-66.8 (c 0.774, CHCl3)

1-[3′-β-Cholest-5′-en-3′-oxy-methyl]-methyl-5-(S)-2-pyrrolidone-5-carboxylateC34H55O4N[α]D20=-55.6 (c 1.86, CHCl3)

1-[17′-β-(1-Ketoethyl)-Δ5′-androsten-3′-β-oxy-methyl]-methyl-5-(S)-2-pyrrolidone-5-carboxylateC28H41O5N[α]D20=-22.8 (c 0.745, CHCl3)