UC San Diego

This work describes mechanistic studies into a ruthenium-mediated cycloaromatization of dienynes. The results of deuterium labeling experiments are consistent with a mechanism that proceeds via a 6-electrocyclization to form an 4-isobenzene adduct followed by a metal-mediated [1,5]-hydride shift. The cycloaromatization of dienynes with substituents in the E-position of the distal alkene is proposed to give arene product via a process involving two sequential [1,2]-hydride shifts. Dienynes bearing phenyl substituents in either the E or Z-position of the distal alkene or acetylenic position were shown to cycloaromatize.

The ruthenium-mediated cycloaromatization of acyclic trienes was accomplished in excellent yields. Observation and characterization of an 6-triene ruthenium complex were accomplished. Deuterium labeling experiments led to a mechanistic proposal involving 6-complexation of ruthenium to the triene followed by disrotatory electrocyclic ring closure. The deprotonation of the 4-1,3-cyclohexadiene intermediate is proposed to generate a cyclohexadienyl ligand, which aromatizes via a ruthenium-assisted protolytic cleavage of a C-H or C-C bond.

In continuation of catalytic metal-triggered cyclization of enediynes under photolytic conditions, the effects of sterics and electronics in Cp-ligated iron and ruthenium were investigated with the 1,2,3,4-tetramethyl-5-trifluoromethylcyclopentadienyl (Cp‡) ligand. A series of Cp‡-ligated iron and ruthenium complexes were prepared. Attempts to generate [Cp‡Fe(6-benzene)]PF6 led to activation of all three C-F bonds and the formation of a new (diphenylmethyl)tetramethylcyclopentadienyl ligand. The cyclization of an enediyne bearing a propargylic stereocenter was shown to have similar stereoselectivity for Cp- and Cp‡-ligated ruthenium (1:1), as compared to Cp* (8:2). The photochemical release of naphthalene from ruthenium in the presence of enediynes or dienynes was observed to give cycloaromatized products in excellent yields.

Finally, a recently discovered thermal cyclization of enediynes was extended to include incorporation of chloride or bromide from chloroform or bromoform, respectively. The haloform was demonstrated to react with 1,4-cyclohexadiene to generate hydrogen halide in situ, which then added across an alkyne to produce a cis, cis-dienyne. The chloro and bromo dienyne intermediates were independently prepared and shown to undergo the cyclization. The cyclization is proposed to involve a cascade of pericyclic reactions initiated by either a [1,7]-hydride shift or 6-electrocyclization leading to arene products with different substitution patterns. When iodoform was used, the iodo dienyne was observed at lower temperatures, but the product of a formal Bergman cyclization was the only product observed at higher temperatures. Fluoroform was observed to have no effect on the rate or product of the enediyne cyclization, presumably due to high bond strengths in fluoroform.