A-Level Structural isomerism and stereoisomerism: worked solution

Question

Psilocin can be described as a tryptamine carrying a hydroxyl group at position 4: the indole framework has an -OH at C-4 and a -CH2CH2N(CH3)2 chain attached at C-3. Sketch the Newman projection corresponding to the lowest-energy conformer of psilocin, and justify why this arrangement is favoured.

The rotatable bond of interest is the Cα-Cβ bond of the -CH2-CH2-N(CH3)2 side chain attached at C-3 of the indole. Sight down this bond for the Newman projection. Front atom (nearer carbon, the CH2 bonded to the indole C-3): its three substituents are the bulky indolyl (aromatic) group and two H atoms. Back atom (the CH2 bonded to nitrogen): its three substituents are the -N(CH3)2 group and two H atoms. Lowest-energy conformer: 1. Staggered, not eclipsed. Rotating to a staggered arrangement (substituents on front carbon bisecting the gaps of the back carbon, dihedral 60 degrees between adjacent bonds) removes torsional strain from bond-bond eclipsing repulsions. Eclipsed conformers are higher in energy by the usual torsional barrier. 2. Anti-periplanar placement of the two largest groups. Among the staggered rotamers, the one placing the two bulkiest substituents, the indolyl ring (front) and the -N(CH3)2 group (back), 180 degrees apart (anti) is favoured. This maximises their separation and minimises steric (van der Waals / gauche) strain between the large aromatic system and the dimethylamino group. So the Newman projection shows: front carbon with indolyl pointing (say) straight up and its two H's at lower-left and lower-right; back carbon with -N(CH3)2 pointing straight down (anti to indolyl) and its two H's at upper-left and upper-right, each H staggered relative to the front substituents. Justification summary: the anti-staggered conformer simultaneously (a) is staggered, eliminating torsional strain, and (b) is anti about the two largest groups, minimising steric repulsion, giving the global energy minimum for rotation about this bond.