Past exam of the chemistry B course of the University of Cambridge / 2021 / Paper 1 / B3 / c

Number the nitrogen N1, the phenyl-bearing carbon C2, and then continue through C3–C6 around the piperidine. Call the solid-wedge epoxide face up; the phenyl group is down in both starting structures. The bulky phenyl group favors a pseudoequatorial orientation.

epoxide opening follows the Fürst-Plattner preference for a chair-like, trans-diaxial opening trajectory. Attack at the two epoxide carbons is not equivalent: the favored route evolves toward an ordinary chair, whereas the alternative demands a less favorable twist/boat-like distortion. Such conformational control of epoxy-2-arylpiperidine opening is supported by synthetic studies.^[ref]

For the first epoxide, azide attacks C5 from down, breaking the C5–O bond. The residual C4–O bond is retained, so work-up gives C5–N3 down and C4–OH up, with the original C2–Ph down. For the second, down-face epoxide, azide attacks C4 from up, leaving C4–N3 up and C5–OH down. These assignments are shown in the middle row of the original stereochemical map.

In each mechanism an azide terminal nitrogen attacks the epoxide carbon, the C–O bonding pair goes to oxygen, and protonation gives the alcohol. Each attacked center inverts, and the azide and OH are trans. The phenyl-bearing center is unchanged. Reversing the epoxide face changes which carbon has the favored axial attack trajectory; a steric rule based only on distance from phenyl misses that conformational effect.