Saturday, July 11, 2009

synthesis of the highly strained 3-aza-[7]-paracyclophane core of haouamines

by Pete Wift
organic letters 2006 1901.

failed methods:
1. various macrolactamization conditions (Scheme 1).
2. synthesis of medium-ring biaryl compounds by organocuprate oxidation also failed (Scheme 2).
3. ring contraction strategy. (Scheme 3)

finally successful method:
As an alternative to the more traditional strategies for overcoming the kinetic barriers of ring closure, we envisioned the preparation of a macrocyclic ring composed of a tetrahydro derivative and subsequently an introduction of the ring strain by altering the hybridization of C from sp3
to sp2 by elimination of methanol. Tautomerization to the phenol would result in the formation of the biaryl system(Scheme 4).

Interestingly, this paper came out about the same time as Baran's first total synthesis (receive date).

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