Past exam of the chemistry course of the year 3 of the natural sciences course of the University of Cambridge / 2022 / Paper 4 / 55 / c

The alcohol first attacks CDI, forming an activated O-carbonylimidazole derivative. Its departure gives the resonance-stabilized propargyl/allenyl cationThe ortho amino nitrogen attacks the central carbon of the allenyl system, closing the five-membered indole ring. Electron redistribution and loss of the N-H proton establish the indole aromatic system while leaving a carbene at the original distal, phenyl-bearing alkyne carbon.

For atom tracking, the original carbinol carbon becomes indole C3, the proximal alkyne carbon becomes C2, and the distal $\mathrm{C}(\mathrm{Ph})$ becomes the exocyclic carbene. Attack at the distal alkyne carbon would make a six-membered ring and cannot give the displayed skeleton. This carbene-based rearrangement has a primary experimental precedent.^[ref]

With an N-trityl substituent, the carbene attacks a nearby trityl phenyl ring. Addition across an arene bond gives a norcaradiene-like cyclopropane, followed by electrocyclic opening to the seven-membered cycloheptatriene: this is a Buchner ring expansion. Intramolecular trapping explains the fused product rather than an intermolecular carbene reaction.

With N-tert-butyl, there is no pendant arene. Instead the carbene inserts into a C-H bond of one tert-butyl methyl group. The new bond between the carbene carbon and that methyl carbon closes the five-membered N-containing ring; H is transferred to the carbene carbon in the same insertion. The remaining two methyl groups stay on the carbon attached to N.

No stereochemical information need survive from the starting carbinol. Ionization converts that tetrahedral stereocentre into a planar, delocalized propargyl/allenyl cation before cyclization. In achiral conditions the two enantiomeric pathways to the new stereocentre in the tert-butyl-derived product are equivalent, so an enantiopure alcohol is expected to give racemic product. A claim of retained enantiopurity would require evidence for unusually effective conformational memory or ion-pair control.