Studies of Chiral Indoles. Part II: Conformational Analysis of 1- and 3-(1-Phenylethyl) Indoles. A Dynamic 1H NMR, Molecular Mechanics, and Circular Dichroism Investigation.

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Abstract
The orietation of the 1-phenylethyl group in a series of 1- and 3-(1-phenylethyl)indoles was investigated by dynamic 1H NMR and circular dichroism (CD) spectroscopy and by molecular mechanics calculation (MM2 force field). The 1-phenylethyl group was shown to adopt both a syn and an anti conformation, the equilibrium depending on the steric size of the substituent in position 2 (R2). The study indicated similar syn-anti equilibria with the 1-phenylethyl group in 1 and 3 position when R2 = H or CH3. However, when R2 = C(CH3)2OH or -C(CH3) = CH2, the 1-(1-phenylethyl)indoles showed strongly dominating syn conformations, while the temperature dependence of the CD spectra indicated that the 3-analogues had less biased syn-anti equilibria. 1H DNMR showed that 1-methyl-2-isopropenyl-3-(1-phenylethyl)indole underwent hindered rotation of the isopropenyl group between two nearly equally populated sites, while the temperature-dependent CD spectrum indicated another more biased exchange, identified as the syn-anti exchange of the 1-phenylethyl group with a lower barrier and a dominant syn form. The rotational strengths obtained by theoretical calculations for the indole 1Lb and 1La transitions are in reasonably good agreement with those found experimentally.