Effects of Chemical Structure on the Thermodynamic Efficiency of Radical Chain Carriers for Organic Synthesis

Abstract

The chain carrier index (CCI), defined as the ratio of the bond dissociation free energies (BDFE) of corresponding chain carrier halides and hydrides, is proposed as a measure of the thermodynamic efficiency of chain carriers for radical dehalogenation. The larger this value is relative to the corresponding value of the organic substrate, the more thermodynamically efficient the process. The chloride and bromide CCIs were evaluated at the G3(MP2)-RAD(+) level of theory for 120 different R-groups, covering a broad range of carbon-centered and noncarbon-centered species; the effects of solvent and temperature have also been studied. The broad finding from this work is that successful chain carriers generally maximize the strength of their halide (versus hydride bonds) through charge-shift bonding. As a result, the thermodynamic efficiency of a chain carrier tends to increase down the periodic table, and also with the inclusion of stronger electron donating substituents. The CCIs of carbon-centered species fall into a relatively narrow range so that, even when the CCI is maximized through inclusion of lone pair donor OMe or NMe(2) groups, the thermodynamic driving force for dehalogenation of other organic substrates is modest at best, and the process is likely to be kinetically hampered. Among the noncarbon-centered species studied, bismuth- and borane-centered compounds have some of the highest CCI values and, although their kinetics requires further optimization, these classes of compounds would be worth further investigation as tin-free radical reducing agents.

Hydrogen Atom Abstraction Thermodynamics of a μ-1,2-Superoxo Dicopper(II) Complex

“…The ability of 3 to abstract H-atoms from weak C–H bonds was then tested. No reaction was observed with 9 H -fluorene (BDFE of the weakest C–H bond 77 kcal mol –1 ) and 9,10-dihydroanthracene (75 kcal mol –1 ) as expected, and also substrates with BDFEs similar to 2 such as thioxanthene (73.7 kcal mol –1 ) or 1,4-cyclohexadiene (72.9 kcal mol –1 ) are not attacked. Steric encumbrance of the Cu-(O 2 • )-Cu moiety in 3 , similar to what was observed crystallographically for the parent peroxo complex 1 , may play a role as this likely prevents the formation of a precursor complex between substrate and 3 prior to the actual CPET.…”

Monovalent Nickel-Mediated Radical Formation: A Concerted Halogen-Atom Dissociation Pathway Determined by Electroanalytical Studies

“…Cyclohexyl iodide reacted substantially faster than cyclohexyl bromide. Plotting the Δ G ⧧ of these reactions as a function of the bond dissociation free energy (BDFE) of the carbon–halogen bonds gave a linear correlation with a slope of 0.24 (Figure B) …”

Radical Arene Addition vs Radical Reduction: Why Organometal Hydride Chain Reactions Stop and How To Make Them Go

“…From these findings for stannane synthesis reactions, it is clear that the success of a radical-chain method relies largely on the reagent’s capacity to reduce not just the propagating radicals but also any delocalized radicals from chain-transfer side reactions of the substrate, reagent, solvent, initiator, impurities, and products. The combination of the weak tin hydride bond, strong tin halide bonds, , selective halide abstraction, and (less obviously) weakness of Sn –C bonds has for decades made stannane reduction the go-to method (the blade in the Swiss Army knife) of radical synthesis. − Yet, in spite of its most excellent chain, the Holy Grail for free-radical synthesis has long been to replace the organotin hydride with more benign and scalable radical-chain reagents. The biggest stumbling block in this quest for tin-free solutions − has been the short chain or, judging from initiator requirements (eq ), the absence of chain.…”