Remote Stereochemical Control of Both Reacting Centers in Ketyl-Olefin Radical Cyclizations: Involvement of a Samarium Tridentate Ligate

High diastereoselection in a samarium(II) iodide-promoted
ketyl-olefin cyclization reaction has been achieved
using tartramide-derived keto allylic acetals as chiral auxiliaries.
The unique features of the reaction include the
fact that remote diastereoselection is achieved in a radical process
and that high levels of stereochemical induction
are observed at both new stereocenters created in the transformation.
The source of the asymmetric induction is
postulated to be a highly ordered, tricyclic transition structure made
possible by three-point chelation between the
ketyl intermediate and the samarium counterion. As such, this
transformation also demonstrates the first example
of the use of a chelating metal to affect high levels of remote
asymmetric induction in a radical reaction. Because
of this chelation, the sense of relative stereoselectivity is unusual
for a SmI2-mediated cyclization, providing
consistently
high ratios of cis/trans isomers. A
double-diastereodifferentiating experiment provides additional support
for this
mechanistic hypothesis. The preparation of enantiomerically
enriched cyclopentanediols and -lactols can be achieved
through this novel asymmetric cyclization protocol.