UC San Diego
Investigations into novel modes of reactivity and stereoselectivity for the cycloaromatization of conjugated enediynes and dienynes
- Author(s): Hitt, David M.
- et al.
This work begins with a review of practical cycloaromatization methodologies utilizing 1,3-dien-5-yne subunits. As a valuable addition to this body of literature, an ambient temperature dienyne cycloaromatization pathway resulting from the formal CH activation of an allylic methyl group and subsequent alkyne 1,2-insertion triggered by cationic cyclopentadienyl ruthenium complexes (CpRu) has been discovered. This cyclization route is fundamentally different to previous studies with CpRu that resulted in the formal Hopf product and the new reactivity appears to be correlated with the bulk of the alkyne substituent. Mild levels of catalysis and selectivity have been observed for cis-1-allylic substituted dienynes, although trans-allylic dienynes were also found to be viable substrates for the stoichiometric reaction. Three transient ruthenium-dienyne complexes have been identified from the reaction of a TMS substituted dienyne, one of which is derived from the trans-1-allylic dienyne and the other two appear to be in equilibrium by ligand exchange as supported by VT NMR studies. Kinetic investigations have ruled out metal [eta]²-alkyne coordination as the reaction-triggering event as previously proposed in similar transformations. Two reaction pathways currently being considered are a [1,7]-hydrogen shift mechanism and a metal C-H insertion mechanism. In continuation of previously described metal-triggered cycloaromatizations of dienynes and enediynes, we have investigated in situ stereoselective [eta]⁶-complexation of the products from these reactions by use of chiral substrates. Use of allylic or propargylic stereocenters led to diastereomeric ratios (d.r.) as high as 8:2. The highest stereoselectivities were found by use of a Cp* versus a Cp ligand and the relative stereochemistry for the major and minor products for both reactions were found to be consistent by X-ray structure characterization. Arene binding experiments have ruled out a mechanism in which the selective binding step occurs by complexation of the free arene. Finally we have uncovered a mode of cycloaromatization for enediynes unrelated to the Bergman mode. The reaction occurs predominately in CDCl3 and is promoted by 1,4-cyclohexadiene and HCl. Intermediacy of a cis,cisyne is suspected and the current mechanistic hypothesis involves a cascade of pericyclic reactions leading to product initiated by a [1,7]-hydrogen shift from the dienyne