Effects of α-alkoxy substitution and conformational constraints on 6-exo radical cyclizations of hydrazones via reversible thiyl and stannyl additions

Access to multifunctional hydrazones of relevance to dysiherbaine synthesis studies is described. Subsequent radical cyclizations of multifunctional hydrazones via a Si- and C-linked tethering strategy are shown to function effectively in 6-exo fashion. Conformational constraints are proposed to play a key role in suppressing unproductive premature reduction pathways. The stereochemical outcomes suggest that minimizing the dipole repulsion between neighboring Cdouble bond; length as m-dashN and C–O bonds favors a Cα–C(double bond; length as m-dashN) dihedral angle placing the Cdouble bond; length as m-dashN bond axial within a chairlike transition state, in contrast to the usual Beckwith–Houk model.