Impact of reducing agent, temperature, and substrate topology on diastereoselectivity of the intermolecular coupling reactions, or how “free” are cobalt-complexed propargyl radicals?

Abstract

Applicability of the term "free radical" to organometallic radicals was studied by using the stereoselectivity of radical C-C bond formation as a diagnostic tool. Based on diastereoselectivity data, it was concluded that the reduction of π-bonded, Co2(CO)6-complexed propargyl cations with heterogeneous reducing agents (Zn, Mg) generates "free radicals", while homogeneous reductants (Cp2Co, Na-Ph2CO) produce "sequestered radicals", presumably associated with reductant-derived oxidized species. The latter are comparable in molecular volume to the requisite radical species, thus restricting the motion and conformational freedoms of converging, transition metal-complexed propargyl radicals. Diastereoselectivity of intermolecular reactions is determined to be much less sensitive toward temperature variation (Δde = 6-22%) than in intramolecular radical cyclizations (Δde = 106%).

Propargyl Radical Chemistry: Renaissance Instigated by Metal Coordination

“…Thus, propargyl radicals generated with either Zn or Mg are the closest to a truly “free radical”. Remarkably, the diastereoselectivities observed for both heterogeneous reductants are close to each other (Zn 84% d , l ; Mg 80% d , l ), further emphasizing the commonality of the species involved. (2) In the case of soluble reductants (Cp 2 Co, Na/Ph 2 CO), the respective oxidized species supposedly remain associated with radicals as a radical-ion pair (entries 3, 4).…”

“…Based on the totality of the experimental data, which involves a number of topologically diverse substrates and reducing agents, we concluded that Co 2 (CO) 6 -complexed propargyl radicals, in general, are not kinetically independent species and cannot be categorized as “free”. Their nature depends upon the reducing agents, which in turn can be separated into three distinct categories (Table ): (1) In the case of heterogeneous reductants (Zn, Mg), the precipitation of inorganic salts derived from the reducing agents limits their ability to remain associated with radical species (entries 1, 2).…”

“…An X-ray crystallographic study revealed the intimate structural details of the propargyl triad with the cationic center being ideally sp 2 -hydridized and through-space coordination causing a structural asymmetry and noticeable shift toward one of the cobalt atoms. In intermolecular coupling reactions, an optimized experimental protocol involves the treatment of propargyl alcohol 15 with a 6-fold excess of tetrafluoroboric acid at 0 °C (Scheme ). The protonation of a hydroxyl group releases propargyl cation 16 , which readily precipitates in ether due to the significant stabilization by a π-bonded Co 2 (CO) 6 core ( Nicholas cation ) .…”

“…Decomplexation with ceric ammonium nitrate was carried out at low temperatures (−78 °C) to release organic dimers 19 in high yields. The scope of the reaction was expanded in a two-dimensional fashion with a variety of substituents being introduced into α- and γ-positions of the propargyl triad (Table ). ,,,− The conditions and yields for the cation generation step are dependent upon π-donating power of α substituents, with α-aryl groups being clearly preferential to α-alkyl (2°) and α-H (1°) counterparts. In contrast, the rate of reduction is lower with the propargyl cations in which the positive charge is reduced due to the efficient delocalization over aromatic nuclei.…”

“…In the course of the systematic studies on the chemistry of metal-bonded propargyl radicals, − ,,− we found that the diastereoselectivity of radical dimerization reactions is dependent upon the nature of the reducing agent as well as the reaction temperature (Scheme ). The said notion seems to be counterintuitive since the very term “free radical” implies that the generation method should not affect the stereochemical outcome of the dimerization reactions.…”