Novel cobalt-mediated regio- and stereoselective radical cyclizations.

Abstract

Initial efforts focused on the intermolecular additions of the radicals to electron deficient double bonds, but they were unsuccessful. Efforts then focused on intramolecular cyclizations of 1-[(alkynyl)Co2(CO) 6]-5-hexenyl systems. Initially, the radicals were generated by the reduction of the complexed cations with zinc. They cyclized to produce the 5-exo products in low yield. Improvement of the yields was unsuccessful, so a method was developed in which the radicals could be generated directly from (propargyl bromide)Co2(CO)6 complexes. It was serendipitously discovered that when neat samples of the bromides were irradiated, bromine atom transfer occurred with novel regioselectivity (5- exo vs. 6-endo) and exceptionally high trans stereoselectivity in the cases where the 5-exo products were formed. Photochemical cyclizations were also attempted on the homologous 1-[(alkynyl)Co2(CO)6]-6-heptenyl bromide complexes. Cyclization was observed in one case in low yield, and only the 7-endo product was observed.

In order to explain these findings, a mechanism has been postulated in which the reactions take place via a radical cyclization under kinetic control but proceed through a late transition state. This mechanism adequately explains our results, but it does not rule out the possibility that the reactions proceed by a non-radical pathway, or are thermodynamically controlled. Mechanistic studies have been performed, to determine whether cyclization proceeds by a radical, reversible pathway, but the results were inconclusive. However, they did not discredit the proposed mechanism.

Finally, the synthetic utility of (propargyl bromides)Co2(CO) 6 was explored and resulted in the successful development of a tandem cyclization/allylation reaction. The product from this reaction was designed so that it could be employed in a Pauson-Khand reaction. Unfortunately, this reaction was not successful.

Initial studies of (propargyl)Co2(CO)6 radicals demonstrated that they dimerize with very good regio- and stereoselectivity. However, very little was known about the general reactivity of such species. For this reason, the goal of this project was to investigate the reactivity of (propargyl)Co2(CO)6 radicals by studying their addition to double bonds of varying electronic character with the hope that they could later be used in synthetically useful methodologies.