Cyclopropylcarbinyl-Type Ring Openings. Reconciling the Chemistry of Neutral Radicals and Radical Anions

The electron-transfer (ET) reduction of two diphenyl-substituted bicyclic endoperoxides was studied in N,N-dimethylformamide by heterogeneous electrochemical techniques. The study provides insight into the structural parameters that affect the reduction mechanism of the O-O bond and dictate the reactivity of distonic radical anions, in addition to evaluating previously unknown thermochemical parameters. Notably, the standard reduction potentials and the bond dissociation energies (BDEs) were evaluated to be -0.55+/-0.15 V and 20+/-3 kcal mol(-1), respectively, the last representing some of the lowest BDEs ever reported. The endoperoxides react by concerted dissociative electron transfer (DET) reduction of the O-O bond yielding a distonic radical-anion intermediate. The reduction of 1,4-diphenyl-2,3-dioxabicyclo[2.2.2]oct-5-ene (1) results in the quantitative formation of 1,4-diphenylcyclohex-2-ene-cis-1,4-diol by an overall two-electron mechanism. In contrast, ET to 1,4-diphenyl-2,3-dioxabicyclo[2.2.2]octane (2) yields 1,4-diphenylcyclohexane-cis-1,4-diol as the major product; however, in competition with the second ET from the electrode, the distonic radical anion undergoes a beta-scission fragmentation yielding 1,4-diphenyl-1,4-butanedione radical anion and ethylene in a mechanism involving less than one electron. These observations are rationalized by an unprecedented catalytic radical-anion chain mechanism, the first ever reported for a bicyclic endoperoxide. The product ratios and the efficiency of the catalytic mechanism are dependent on the electrode potential and the concentration of weak non-nucleophilic acid. A thermochemical cycle for calculating the driving force for beta-scission fragmentation is presented, and provides insight into why the fragmentation chemistry of distonic radical anions is different from analogous neutral biradicals.

Section: Introductionmentioning

confidence: 99%

A Radical‐Anion Chain Mechanism Initiated by Dissociative Electron Transfer to a Bicyclic Endoperoxide: Insight into the Fragmentation Chemistry of Neutral Biradicals and Distonic Radical Anions

Magri

Workentin

2008

“…[ 35] The results summarized in Table 4 indicate that under the mild conditions used the Ti-catalyzed procedure is compati- ble with different functional groups, including alkyl halides, phenols, and ketals. Moreover, the easy lactonization that occurred after the allylation of keto ester 43 suggested that this procedure might become a useful tool for the synthesis of g-lactones.…”

Section: Resultsmentioning

confidence: 99%

Ti‐Catalyzed Barbier‐Type Allylations and Related Reactions

Estévez

Justicia

Bazdi

et al. 2009

Titanocene(III) complexes, easily generated in situ from commercial Ti(IV) precursors, catalyze Barbier-type allylations, intramolecular crotylations (cyclizations), and prenylations of a wide range of aldehydes and ketones. The reaction displays surprising and unprecedented mechanistic subtleties. In cyclizations a fast and irreversible addition of an allyl radical to a Ti(III)-coordinated carbonyl group seems to occur. Intermolecular additions to conjugated aldehydes proceed through a coupling of a Ti(IV)-bound ketyl radical with an allyl radical. Reactions of ketones with allylic halides take place by the classical addition of an allylic organometallic reagent. The radical coupling processes enable transformations such as the highly regioselective alpha-prenylation that are otherwise difficult to achieve. The mild reaction conditions and the possibility to employ titanocene complexes in only catalytic quantities are highly attractive features of our protocol. These unusual properties have been taken advantage of for the straightforward synthesis of the natural products rosiridol, shikalkin, and 12-hydroxysqualene.

“…However, a body of work by Tanko and coworkers has provided evidence that this assumption is not necessarily valid. [3][4][5][6] They demonstrated by electrochemically generating a series of cycloalkylketone radical anions that both charge and spin are governing factors in the reactivity of radical-anion rearrangements. The radical anions in these studies were observed to undergo a carbon-carbon bond fragmentation yielding a single species containing a spatially separated radical and anion, which is otherwise known as a distonic radical anion [Eq.…”

Section: Introductionmentioning

confidence: 99%

“…Discrepancies between the rates constants for fragmentation of radical-anions and their neutral radical counterparts are only recently becoming known. [3,4,7,8] For the fragmentation of 2 a, it is suggested that the alkoxyl anion is more readily stabilized by the aryl rings than the alkoxyl radical center. This assessment agrees with the trend in the fragmentation rate constants as 2 d has the lowest value as the 4-nitrophenyl rings provide the greatest stabilizing effect on the alkoxide anion.…”

mentioning

confidence: 99%

Efficient Homogeneous Radical‐Anion Chain Reactions Initiated by Dissociative Electron Transfer to 3,3,6,6‐Tetraaryl‐1,2‐dioxanes

Stringle

Magri²,

Workentin

2009

A series of 3,3,6,6-tetraaryl-1,2-dioxanes (TADs) have been investigated at an inert electrode by using cyclic voltammetry, constant potential electrolysis and digital simulations. The series consists of the phenyl-substituted TAD (1 a), p-methoxy-aryl TADs (1 b, 1 c) and the p-methoxy/nitro-bearing TAD (1 d). The heterogeneous electron-transfer (ET) reduction is dissociative, causing rupture of the oxygen-oxygen bond, which generates a distonic radical-anion that reacts competitively either by beta-scission fragmentation or ET. Fragmentation of the distonic radical anion yields an alkene, a substituted benzophenone, and a benzophenone radical anion. The benzophenone radical-anion propagates an efficient homogeneous ET-fragmentation chain reaction that accounts for the potential dependence of the product ratios and the low charge consumption observed in the controlled potential electrolysis experiments. Digital simulation of the experimental cyclic voltammograms allowed for estimates of the rate constants of the heterogeneous ET to the O--O bond, and for the rate constants for the beta-scission fragmentation of the distonic radical-anions. Density functional theory calculations corroborate the differences in the heterogeneous kinetics of the initial dissociative ET. The endoperoxides 1 a-1 c react predominantly by a concerted dissociative ET mechanism, although the data suggests a stepwise dissociative pathway is also competitive. Bearing a nitro-aryl substituent, 1 d provides a rare example of an endoperoxide that proceeds by a stepwise dissociative ET mechanism. Irrespective of the initial mechanistic details, we find a propagating radical-anion cycle is a general mechanistic feature.