Powerful Solvent Effect of Water in Radical Reaction:  Triethylborane-Induced Atom-Transfer Radical Cyclization in Water

Abstract

Triethylborane-induced atom-transfer radical cyclization of iodo acetals and iodoacetates in water is described. Radical cyclization of iodo acetal proceeded smoothly both in aqueous methanol and in water. Atom-transfer radical cyclization of allyl iodoacetate (3a) is much more efficient in water than in benzene or hexane. For instance, treatment of 3a with triethylborane in benzene or hexane at room temperature did not yield the desired lactone. In contrast, 3a cyclized much more smoothly in water and yielded the corresponding γ-lactone in high yield. The remarkable solvent effect of water was observed in this reaction, although the medium effect is believed to be small in radical reactions. Powerful solvent effects also operate in the preparation of medium- and large-ring lactones. Water as a reaction solvent strikingly promoted the cyclization reaction of large-membered rings. Stirring a solution of 3,6-dioxa-8-nonenyl iodoacetate in water in the presence of triethylborane at 25 °C for 10 h provided a 12-membered ring product, 4-iodo-6,9-dioxa-11-undecanolide, in 84% yield. On the other hand, reaction in benzene afforded the lactone in only 22% yield. Ab initio calculations were conducted to reveal the origin of the solvent effect of water in the cyclization of allyl iodoacetate. Calculations with the SCRF/CPCM option indicate that the large dielectric constant of water lowers the barrier not only to rotation from the Z-rotamer to the E-rotamer that can cyclize but also to cyclization constructing the γ-lactone framework. Moreover, the high cohesive energy density of water also effects acceleration of the cyclization because water forces a decrease in the volume of the reactant.

Water‐ and Acid‐Mediated Excited‐State Intramolecular Proton Transfer and Decarboxylation Reactions of Ketoprofen in Water‐Rich and Acidic Aqueous Solutions

“…[36][37][38][39][40][41] Waluk and co-workers found that hydrogen-bonded complexes with one or two water molecules will greatly decrease the energy barrier for a protontransfer reaction. DFT calculations also found that 7-azaindole clustered with four water molecules could explain the rate increase relative to the 7-azaindole monomer clustered with two and three water molecules.…”

Absolute Rate Constants of Alkene Addition Reactions of a Fluorinated Radical in Water

“…However, a report last year indicated that triethylborane-induced atom transfer radical cyclization reactions proceeded much more effectively in water than in the traditional organic solvents. 16 In contrast to the relative lack of data in the organic literature, water has long been a popular solvent for carrying out freeradical polymerizations, 17,18 especially of fluorinated monomers. 19 Although most fluoropolymers are now made by dispersion, emulsion, or suspension polymerizations in aqueous media, there are still problems associated with this field that make studies of absolute rates of fluoroalkyl radicals in water of some importance.…”

Tin-Free Radical Reactions Mediated by Organoboron Compounds

“…14a) [36], iodoamides [37], α-iodonitriles [36], and simple alkyl iodides [38] to alkenes and alkynes have been reported. Interestingly, these reactions were also performed with success in aqueous media [13,39,40] demonstrating the ability of Et 3 B to act as initiator in water (Eq. 14b) [41].…”