Acquiring a Prognostic Power in Co₂(CO)₆-Mediated, Cobaltocene-Induced Radical Dimerizations of Propargyl Triflates

Abstract

Cobalt-complexed propargyl triflates can be generated in situ from methyl propargyl ethers and triflic anhydride and then reduced with cobaltocene to topologically and functionally diverse 1,5-alkadiynes. The electronic effect of an α-substituent is shown to attenuate the ionic nature of an α-C−OTf bond and thus its reducibility with cobaltocene. The powerful π-donors, such as phenyl, naphthyl, alkenyl, alkynyl, and alkoxy groups, provide the ionicity of α-C−OTf bonds and make them suitable recipients for a single-electron delivery from cobaltocene. σ-Donors (alkyl groups), a H atom, and σ/π-acceptors (ester groups) do not sufficiently stabilize propargyl cations, maintaining the covalent nature of α-C−OTf bonds and making them resistant toward the reducing agent. A newly acquired ability to differentiate between the α-C−OTf bonds is used in polyethers for the regioselective reduction and radical dimerization in select propargylic positions, thus paving the way for a long sought after radical-ionic α,α′-functionalization in propargyl systems. Heterolytic bond dissociation energy (BDE) values are used to quantitate the impact of alpha substituents, to identify the "ionic" and "covalent" domains for electronically diverse propargyl triflates (ionic: BDE het 238−271 kcal/mol; covalent: BDE het 277−315 kcal/mol), and also to make predictions for new types of substituents and new classes of organic compounds.

Cobalt-Mediated Radical Cyclizations: Stereoselective Synthesis of Cyclopentanes, Cyclohexanes, and Tetralins

“…In the previous studies, the most common type of alpha substituent in Co 2 (CO) 6 -complexed propargyl alcohols has been π-donors such as an aromatic ring, − an oxygen atom, or double and triple bonds. Their ability to stabilize propargyl cations substantially accelerated the formation of reactive intermediates, thus facilitating their isolation and subsequent reduction steps.…”

“…In cobalt-alkyne radical chemistry, , 1,3-steric induction was first described for intermolecular reactions of Co 2 (CO) 6 -complexed propargyl alcohols . Incorporation of bulky substituents at the acetylenic termini (γ- t -Bu, γ-TMS) allowed for complete steric control over converging radicals and exclusive formation of the respective d , l -diastereomers .…”

“…Over the last two decades, systematic studies on cobalt-mediated coupling reactions in propargyl systems resulted in the development of novel methods for radical generation, expansion of the temperature domain wherein the π-complexed propargyl radicals could function (−78 to +147 °C), uncovering new types of steric induction upon the configuration of the newly formed stereocenters, discovering spontaneous and tetrahydrofuran (THF)-mediated radical dimerization reactions, establishing an ability of propargyl radicals to be “sequestered” by the reductant-derived molecules, synthesis of metal-complexed cations under nonacidic conditions, and gaining access to the new types of radicals for which methods of generation were either lacking or remained unknown in a purely organic setting (α-alkoxy, α-alkenyl, and α-alkadienyl propargyl radicals). , Due to the bulkiness of a dicobalthexacarbonyl core and the bent structure of alkyne units, , formation of radical C–C bonds, alpha to a metal core, reached the highest levels of stereoselectivity, up to 100% . In comparison to inter molecular coupling reactions, cobalt-mediated intra molecular cyclizations have been studied to a lesser extent, − providing, in particular, a facile four-step access to 1,5-cyclodecadiynes, ,, in good to moderate yields, and selectivities ( d , l / meso ) varying widely, from 67:34 to 5:95 . Requisite bis-cations 1 with varying tether lengths ( n = 2–4) were isolated as dark red solids and reduced in situ with zinc or cobaltocene to their respective diradicals 2 (Figure ).…”