Hydrogen Atom Transfer from Alkanols and Alkanediols to the

Apr 18, 2018 - *E-mail [email protected]. ... Predominant hydrogen atom transfer (HAT) from the α-C–H bonds of these substrates, ... Suzuki–Miya...
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Article Cite This: J. Org. Chem. 2018, 83, 5539−5545

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Hydrogen Atom Transfer from Alkanols and Alkanediols to the Cumyloxyl Radical: Kinetic Evaluation of the Contribution of α‑C−H Activation and β‑C−H Deactivation Michela Salamone, Vanesa B. Ortega, Teo Martin, and Massimo Bietti* Dipartimento di Scienze e Tecnologie Chimiche, Università “Tor Vergata”, Via della Ricerca Scientifica 1, I-00133 Rome, Italy S Supporting Information *

ABSTRACT: A kinetic study on the reactions of the cumyloxyl radical (CumO•) with a series of alkanols and alkanediols has been carried out. Predominant hydrogen atom transfer (HAT) from the α-C−H bonds of these substrates, activated by the presence of the OH group, is observed. The comparable kH values measured for ethanol and 1-propanol and the increase in kH measured upon going from 1,2-diols to structurally related 1,3- and 1,4-diols is indicative of β-C−H deactivation toward HAT to the electrophilic CumO•, determined by the electron-withdrawing character of the OH group. No analogous deactivation is observed for the corresponding diamines, in agreement with the weaker electron-withdrawing character of the NH2 group. The significantly lower kH values measured for reaction of CumO• with densely oxygenated methyl pyranosides as compared to cyclohexanol derivatives highlights the role of β-C−H deactivation. The contribution of torsional effects on reactivity is evidenced by the ∼2fold increase in kH observed upon going from the trans isomers of 4-tert-butylcyclohexanol and 1,2- and 1,4-cyclohexanediol to the corresponding cis isomers. These results provide an evaluation of the role of electronic and torsional effects on HAT reactions from alcohols and diols to CumO•, uncovering moreover β-C−H deactivation as a relevant contributor in defining site selectivity.

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is mostly limited to benzylic alcohols.22 Alcohols and diols constitute very important classes of organic compounds, widely represented in a variety of natural products and biomolecules. Along this line, in keeping with the current interest in the development of HAT-based procedures for the functionalization of alcohol C−H bonds, and in order to provide a deeper understanding of the role played by structural effects on these processes, this paper reports on a detailed time-resolved kinetic study of the reactions of cumyloxyl radical [PhC(CH3)2O•, CumO•] with a series of acyclic and cyclic alkanols and alkanediols, the structures of which are displayed in Chart 1. As a matter of comparison, the kinetic study has been also extended to reactions of CumO• with the cis and trans isomers of 1,2- and 1,4-cyclohexanediamine and with three methyl glycosides, namely, methyl α-D-glucopyranoside, methyl β-Dglucopyranoside, and methyl α-D-mannopyranoside.

INTRODUCTION Selective aliphatic C−H bond functionalization represents an important strategy of modern synthetic organic chemistry that accordingly has found application in an increasing number of synthetically useful procedures.1−4 Among the available methodologies, those based on hydrogen atom transfer (HAT) from aliphatic C−H bonds to radical or radical-like species are attracting considerable interest in view of their versatility and, thanks to the current understanding of the reactivity trends associated with these processes, their ability to promote highly selective transformations.4−12 As a consequence of the electrophilic nature of the majority of the HAT reagents employed in these procedures, with substrates such as amines, amides, carbamates, ureas, alcohols, and ethers, functionalization preferentially occurs at the more electron-rich and activated C−H bonds, that is, the C−H bonds that are α to nitrogen and oxygen.13−15 Kinetic studies on the role of structural effects on HAT from the aliphatic C−H bonds of these substrates have provided an understanding of the factors that govern reactivity and selectivity, strongly contributing to the development of such procedures. However, although extensive kinetic information is available on HAT reactions from the aliphatic C−H bonds of amine,16 amide,17 and ether16b,18 substrates to free radical species, quite surprisingly, little information is available for the corresponding reactions involving alcohol substrates,19−21 and the available information © 2018 American Chemical Society

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RESULTS AND DISCUSSION CumO• has been generated by 355 or 266 nm laser flash photolysis (LFP) of nitrogen-saturated solutions (T = 25 °C) containing 0.01−1.0 M dicumyl peroxide. CumO• is characterized by a broad absorption band in the visible region of the Received: March 1, 2018 Published: April 18, 2018 5539

DOI: 10.1021/acs.joc.8b00562 J. Org. Chem. 2018, 83, 5539−5545

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The Journal of Organic Chemistry Chart 1. Structures of Substrates Studied in This Work

spectrum centered at 485 nm, whose position is red-shifted in protic solvents such as MeOH and trifluoroethanol (TFE). In the absence of hydrogen atom donor substrates, CumO• decays almost exclusively by C−CH3 β-scission.23 Time-resolved kinetic studies on the reactions of CumO• with the substrates displayed in Chart 1 have been carried out by means of the LFP technique. By plotting the kobs values, measured following the CumO• visible absorption band decay, against [substrate], linear correlations have been obtained that lead, from the slope of these plots, to the second-order rate constants for HAT to CumO• (kH). Figure 1 displays the kobs

Table 1. Second-Order Rate Constants for Reaction of Cumyloxyl Radical with Alkanols and Alkanediolsa substrate ethanol 1-propanol 2-propanol 1-butanol 1-pentanol 1-hexanol 1,2-ethanediol 1,2-propanediol 1,3-propanediol

kH (M−1·s−1) (1.15 (1.04 (2.02 (1.18 (1.46 (1.58 (8.4 (1.55 (1.95

± ± ± ± ± ± ± ± ±

0.02) × 106 0.04) × 106 b 0.05) × 106 0.02) × 106 0.07) × 106 b 0.08) × 106 0.1) × 105 0.05) × 106 0.05) × 106

Measured in nitrogen-saturated acetonitrile solution at T = 25 °C employing 355 nm LFP; [dicumyl peroxide] = 1.0 M. bRef 20.

a

taking into account that nonactivated CH3 groups display a low reactivity toward CumO• and t-BuO• (kH ≤ 1.3 × 104 M−1·s−1 per CH3 group),17b,24 the kH values measured with ethanol and 2-propanol and the comparable values measured for the reactions of ethanol and 1-propanol are indicative of selective HAT from the α-C−H bonds of these substrates that are activated by the presence of the OH group. Comparable values have been measured previously for the corresponding reactions of the tert-butoxyl radical (tBuO•) with ethanol and 1-propanol (kH = 1.1 × 106 and 1.8 × 106 M−1·s−1, respectively),19 in line with the similar reactivity displayed by these two tert-alkoxyl radicals in HAT reactions.16 The 2-fold increase in kH measured upon going from 1-propanol to 2-propanol (kH = 1.04 × 106 and 2.02 × 106 M−1·s−1, respectively; 4-fold if normalized for the number of α-C−H bonds) can be accounted for on the basis of weaker α-C−H bonds of secondary alcohols as compared to primary ones.25 The comparable kH values measured for ethanol and 1propanol (kH = 1.15 × 106 and 1.04 × 106 M−1·s−1, respectively) indicate that with the latter substrate HAT from the β-CH2 group does not contribute to any significant extent to kH, a behavior that reflects the deactivation of this position toward HAT to the electrophilic CumO• determined by the electron-withdrawing character of the OH group. An analogous behavior has been previously observed in the rhodium carbeneinduced functionalization of aliphatic C−H bonds where, in the reaction of 1,2-dimethoxyethane, the selective functionalization of the primary C−H bonds α to oxygen over the secondary ones was explained on the basis of the electronic deactivation of the latter bonds toward insertion determined by the inductive effect of the β-oxygen.26 Taken together, these observations point toward β-C−H deactivation as a relevant contributor in defining site selectivity in the reaction of electrophilic reagents with the C−H bonds of alcohol and ether substrates.

Figure 1. Plots of observed rate constant (kobs) vs [substrate] for reaction of CumO• with alkanols and 1,2-alkanediols measured in nitrogen-saturated acetonitrile at T = 25 °C. From the regression analysis: (●) ethanol, intercept = 7.52 × 105 s−1, kH = 1.14 × 106 M−1· s−1, r2 = 0.9994; (○) 2-propanol, intercept = 7.86 × 105 s−1, kH = 1.97 × 106 M−1·s−1, r2 = 0.9998; (■) 1,2-ethanediol, intercept = 7.81 × 105 s−1, kH = 8.30 × 105 M−1·s−1, r2 = 0.9988; (□) 1,2-propanediol, intercept = 7.59 × 105 s−1, kH = 1.59 × 106 M−1·s−1, r2 = 0.9983.

versus [substrate] plots for the reactions of CumO• with (●) ethanol, (○) 2-propanol, (■) 1,2-ethanediol, and (□) 1,2propanediol for measurements carried out in acetonitrile at T = 25 °C. Additional plots for the reactions of CumO• with the other substrates displayed in Chart 1 are collected in Supporting Information as Figures S1−S21. The kH values thus obtained for reaction of CumO• with alkanols and alkanediols and with cycloalkanols and cycloalkanediols are collected in Tables 1 and 2, respectively. We start our analysis from the reactions of CumO• with ethanol, 1-propanol, and 2-propanol in acetonitrile solution. By 5540

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The Journal of Organic Chemistry As compared to ethanol and 1-propanol, the increase in kH measured along the 1-alkanol series can be rationalized on the basis of competitive HAT from the α- and more remote γ-, δ-, and ε-CH2 groups, as discussed recently in a time-resolved kinetic study on the reactions of CumO• with 1-propyl and 1pentyl derivatives.20 Analysis of the results obtained for reactions of CumO• with 1,2-ethanediol, 1,2-propanediol, and 1,3-propanediol nicely supports this mechanistic picture. Accordingly, the decrease in kH measured upon going from ethanol to 1,2-ethanediol and from 2-propanol to 1,2-propanediol (Figure 1) points toward the contribution to the overall reactivity of C−H deactivation determined by the presence of a β-OH group. On the other hand, the almost 2-fold increase in kH measured upon going from 1-propanol to 1,3-propanediol, characterized by two and four C−H bonds α to the OH groups, respectively, indicates that electronic C−H bond deactivation determined by the additional oxygenated group is significantly stronger for the βposition as compared to the γ-position. Moving then to the reactions of CumO• with cycloalkanol substrates in acetonitrile solution (Table 2), the magnitude of

previously on the study of kinetic solvent effects on HAT from the C−H bonds of substrates characterized by the presence of hydrogen-bond acceptor (HBA) functional groups (amines, amides, ethers, and aldehydes) to CumO•,10 this behavior can be explained accordingly in terms of α-C−H deactivation determined by solvent hydrogen bonding to the OH group. This interaction decreases the degree of hyperconjugative overlap between the α-C−H σ* orbital and the oxygen lone pair, leading to an increase in bond strength and to destabilization of the HAT transition state and of the carbon radical formed following HAT. These observations are in full agreement with the results of a recent study on the HAT-based oxidation of alkanols and cycloalkanols with hydrogen peroxide catalyzed by Mn complexes. In this study, fluorinated alcohols such as TFE and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) have been shown to promote strong α-C−H bond deactivation via hydrogen bonding to the substrate OH group, promoting remote C−H bond hydroxylation.27 For example, when the reaction of cyclohexanol with hydrogen peroxide catalyzed by the Mn(TIPSmcp) complex28 was carried out in acetonitrile, formation of cyclohexanone as the exclusive oxidation product was observed (Scheme 1, left). In HFIP, competitive C−H

Table 2. Second-Order Rate Constants for Reaction of CumO• with Cycloalkanols and Cycloalkanediolsa substrate

solvent

cyclobutanol cyclopentanol cyclohexanol cyclohexanol cyclohexanol cyclohexanol cyclohexanol cyclohexanol cis-4-tert-butylcyclohexanol cis-4-tert-butylcyclohexanol trans-4-tert-butylcyclohexanol trans-4-tert-butylcyclohexanol cis-1,2-cyclopentanediol trans-1,2-cyclopentanediol cis-1,2-cyclohexanediol cis-1,2-cyclohexanediol trans-1,2-cyclohexanediol trans-1,2-cyclohexanediol cis-1,4-cyclohexanediol trans-1,4-cyclohexanediol

MeCN MeCN MeCN TFE MeOH MBOHc DMSO isooctane MeCN DMSO MeCN DMSO MeCN MeCN MeCN DMSO MeCNd DMSO DMSO DMSO

Scheme 1. Solvent Effect on Oxidation of Cyclohexanol with Hydrogen Peroxide Catalyzed by Mn(TIPSmcp) Complex

−1 −1

kH (M ·s ) (2.08 (2.50 (2.66 (8.0 (1.3 (2.49 (4.93 (6.3 (5.06 (8.4 (2.37 (3.39 (2.49 (9.3 (2.7 (4.0 (1.43 (1.84 (1.12 (6.6

± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

0.04) × 106 0.02) × 106 0.05) × 106 b 0.5) × 105 0.1) × 106 0.02) × 106 0.06) × 106 0.1) × 106 0.03) × 106 0.2) × 106 0.02) × 106 0.08) × 106 0.02) × 106 0.3) × 105 0.1) × 106 0.3) × 106 0.03) × 106 0.03) × 106 0.02) × 107 0.1) × 106

bond oxidation at the most remote and least deactivated site was observed, evidenced by the formation of cyclohexanone and 1,4-cyclohexanediol in a 1.2:1 ratio (Scheme 1, right). In order to obtain information on the role of α-C−H bond configuration on HAT reactivity, the reactions of CumO• with cis- and trans-4-tert-butylcyclohexanol have been also investigated. With both substrates, the tertiary C−H bond at C4 and the secondary C−H bonds at C3 and C5 are deactivated toward HAT by torsional effects determined by the presence of the bulky tert-butyl group (Scheme 2, red circles).10,29 Moreover, as discussed above, the C−H bonds at C2 and C6, which are β to the OH group, are deactivated by electronic effects (Scheme 2, blue stars). Scheme 2. C−H Bond Deactivation Effects Operating with cis- and trans-4-tert-Butylcyclohexanol

Measured in nitrogen-saturated solution at T = 25 °C employing 355 nm LFP; [dicumyl peroxide] = 1.0 M. bRef 20. c2-Methyl-2-butanol. d Solubility ≤0.4 M. a

the kH values measured for cyclobutanol, cyclopentanol, and cyclohexanol and the increase in kH observed along this series support the hypothesis that with all three substrates HAT predominantly occurs from the tertiary α-C−H bond, with the contribution of competitive HAT from remote methylenic sites that increases with increasing ring size. The reaction of CumO• with cyclohexanol has been also investigated in other solvents, namely, 2,2,2-trifluoroethanol (TFE), methanol, 2-methyl-2-butanol (MBOH), dimethyl sulfoxide (DMSO), and 2,2,4-trimethylpentane (isooctane). A ∼8-fold decrease in kH has been observed upon going from isooctane to TFE, that is, upon increasing solvent hydrogenbond donor (HBD) ability. In keeping with the results obtained

The locked conformation imposed by the tert-butyl group places the tertiary α-C−H bond in equatorial and axial positions for the cis and trans isomers, respectively, and accordingly, the measured kH values should now predominantly reflect HAT from these bonds. The data displayed in Table 2 show a ∼2-fold increase in kH upon going from the trans isomer to the cis isomer (in acetonitrile, kH = 2.37 × 106 and 5.06 × 106 M−1·s−1, respectively), indicative of a greater reactivity 5541

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The Journal of Organic Chemistry toward CumO• of the tertiary equatorial α-C−H bond as compared to the tertiary axial one. Similar behavior has been observed previously in the reactions of cyclohexane and decalin derivatives with HAT reagents and has been interpreted on the basis of torsional effects.29,30 Tertiary equatorial C−H bond activation has been rationalized in terms of a release of 1,3diaxial strain in the HAT transition state resulting from the planarization of an incipient carbon radical. Tertiary axial C−H bond deactivation has instead been rationalized in terms of a torsional strain increase in the HAT transition state due to planarization of an incipient carbon radical that forces the substituent toward an unfavorable eclipsed interaction with the equatorial C−H bonds on the adjacent positions. Along these lines, torsional effects can be also put forward to account for the increase in reactivity observed in the present study upon going from trans- to cis-4-tert-butylcyclohexanol. However, the significantly lower rate constant ratio measured for this substrate couple [kH(eq)/kH(ax) = 2.14] as compared to those measured previously for reaction of CumO• with the cis and trans isomers of 1,2-dimethylcyclohexane, 1,4-dimethylcyclohexane, and decalin [kH(eq)/kH(ax) = 10−14],29 can be explained on the basis of lower intrinsic reactivity of a tertiary hydrocarbon C−H bond as compared to a tertiary alcohol C−H bond, which accordingly magnifies, in the case of hydrocarbon substrates, the relative contribution of torsional effects to the overall reactivity. Comparison between the kH values measured for reaction of CumO• with cyclopentanol and cyclohexanol and those measured for the cis and trans isomers of 1,2-cyclopentanediol, 1,2-cyclohexanediol, and 1,4-cyclohexanediol provides additional information on the contribution of electronic and torsional effects. Almost identical kH values have been measured for cyclopentanol and cis-1,2-cyclopentanediol (kH = 2.50 × 106 and 2.49 × 106 M−1·s−1, respectively) and for cyclohexanol and cis-1,2-cyclohexanediol (kH = 2.66 × 106 and 2.7 × 106 M−1·s−1, respectively), despite the doubled number of tertiary α-C−H bonds displayed by cycloalkanediol substrates as compared to cycloalkanol ones. This behavior reflects once again the deactivating effect determined by the presence of β-OH groups, as discussed above for the corresponding reactions of the alkanols and alkanediols. When it is taken into account that cis-1,2-cyclohexanediol is characterized by the presence of a tertiary equatorial C−H bond, the almost identical kH values measured for this substrate and for cyclohexanol indicate, moreover, that electronic deactivation determined by a β-OH group can counterbalance C−H bond activation induced by torsional effect. As compared to cyclopentanol and cis-1,2-cyclopentanediol, and to cyclohexanol and cis-1,2-cyclohexanediol, the ∼3-fold and 2-fold decrease in kH measured for trans-1,2-cyclopentanediol (kH = 9.3 × 105 M−1·s−1) and trans-1,2-cyclohexanediol (kH = 1.43 × 106 M−1·s−1), respectively, can be explained again on the basis of deactivating electronic effects and the contribution of torsional effects. With these substrates, planarization of the incipient carbon radical in the transition state for HAT from the α-C−H bond to CumO• forces the two OH groups toward an unfavorable eclipsed interaction (Scheme 3), accounting for the observed decrease in kH. Due to the relatively low solubility of cis- and trans-1,4cyclohexanediol in acetonitrile solution, the kinetic study of their reactions with CumO• has been carried out in DMSO. In order to allow a consistent comparison between the measured kH values, the reactions of cyclohexanol, cis- and trans-4-tert-

Scheme 3. Transition Structures for HAT from the α-C−H Bond of trans-1,2-Cyclopentanediol and trans-1,2Cyclohexanediol to CumO•

butylcyclohexanol, and cis- and trans-1,2-cyclohexanediol have been also studied in this solvent. With all of these substrates, an up to ∼2-fold increase in kH has been observed upon going from acetonitrile to DMSO. This systematic increase in reactivity can be explained on the basis of the significantly stronger HBA character of DMSO as compared to acetonitrile,31 that, by engaging in hydrogen bonding with the OH group increases the electron density at the oxygen center, determining an increase in the rate constant for HAT from the α-C−H bonds of these substrates to the electrophilic CumO•. It is worth mentioning that an analogous activation was recently exploited by MacMillan and co-workers15e for α-C−H bond functionalization of alcohol substrates, where hydrogen bonding between an acceptor and the OH group selectively activates these bonds toward HAT to an electrophilic reagent, such as the radical cation of 1-azabicyclo[2.2.2]octane. When the reactivity of 1,2- and 1,4-cyclohexanediols is compared, a ∼2-fold increase in kH has been measured for both couples upon going from the trans isomer to the corresponding cis one, a behavior that reflects also in this case the presence of an activated tertiary equatorial C−H bond in the latter isomers. The ∼3-fold increase in kH measured upon going from 1,2- to 1,4-cyclohexanediols is instead indicative of the increased distance between the two tertiary C−H bonds upon going from the former isomeric couple to the latter one that accordingly will experience a reduced extent of electronic deactivation determined by the presence of a more remote δ- rather than βOH group. Comparison of the kH values measured for reactions of CumO• with cyclohexanediols (Table 2) with those measured for reactions of the corresponding cyclohexanediamines (Table 3) provides information on the role of the electron-withdrawing (EW) character of the functional group on remote C−H bond deactivation. As a consequence of the stronger inductive EW character of the OH group, as compared to NH2, and of the electrophilic character of CumO•, the α-C−H bonds of alkylamines are more electron-rich and thus intrinsically more activated toward Table 3. Second-Order Rate Constants for Reaction of CumO• with Cyclohexylamine and Cyclohexanediaminesa substrate

solvent

cyclohexylamine cyclohexylamine cis-1,2-cyclohexanediamine trans-1,2-cyclohexanediamine cis-1,4-cyclohexanediamine trans-1,4-cyclohexanediamine

MeCN TFE MeCN MeCN MeCN MeCN

kH (M−1·s−1) (2.1 210, respectively].32 Along these lines, comparison between the kH values displayed in Table 2 and Table 3 shows that cyclohexanediamines undergo HAT to CumO• with rate constants that always exceed those measured for reactions of the corresponding cyclohexanediols. In particular, with the 1,2-isomers, where the measurements have been carried out in the same solvent, acetonitrile, a 24-fold increase in kH has been observed for both cis and trans isomers. Most interestingly, however, and in contrast with the results discussed above for cis- and trans-1,2and -1,4-cyclohexanediols, an up to 3-fold increase in kH has been measured upon going from cyclohexylamine to cis- and trans-1,2-cyclohexanediamine, clearly indicating that in the presence of NH2 groups strong deactivation of the tertiary C− H bonds that are β to these groups no longer operates. This observation is supported, moreover, by the comparable kH values measured for trans-1,2- and trans-1,4-cyclohexanediamine (kH = 3.44 × 107 and 3.31 × 107 M−1·s−1, respectively) and for cis-1,2- and cis-1,4-cyclohexanediamine (kH = 6.58 × 107 and 5.54 × 107 M−1·s−1, respectively), showing that reactivity is essentially not affected by the position of the remote NH2 group. The almost 2-fold increase in kH measured for both cyclohexanediamine isomeric couples upon going from the trans isomer to the cis one is again indicative of the presence of an activated tertiary equatorial C−H bond in the latter isomers. Finally, the importance of these electronic deactivating effects is highlighted by the results obtained in the timeresolved kinetic study on reactions of CumO• with methyl α-Dglucopyranoside, methyl β-D-glucopyranoside, and methyl α-Dmannopyranoside, all characterized by the presence of 10 C−H bonds that are α to oxygen atoms. Although the kinetic data do not provide information on the site selectivity of the HAT reaction, as compared to cyclohexanol derivatives [for which kH(DMSO) = (3.4−8.4) × 106 M−1·s−1; see Table 2], a significant decrease in kH has been measured for all three substrates (Scheme 4), indicative of a relatively strong deactivation of these densely oxygenated substrates toward electrophilic HAT reagents. This is a striking observation if one considers, in particular, that such substrates are readily oxidized via ionic pathways by a number of reagents.33

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EXPERIMENTAL SECTION

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ASSOCIATED CONTENT

Materials. Spectroscopic-grade 2,2,4-trimethylpentane (isooctane), 2-methyl-2-butanol (MBOH), dimethyl sulfoxide (DMSO), acetonitrile, methanol, and 2,2,2-trifluoroethanol (TFE) were used in the kinetic experiments. Dicumyl peroxide, ethanol, 2-propanol, 1-hexanol, 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, cyclobutanol, cyclopentanol, cyclohexanol, cis- and trans-4-tert-butylcyclohexanol, cis- and trans-1,2-cyclopentanediol, cis- and trans-1,2-cyclohexanediol, cis- and trans-1,4-cyclohexanediol, cis- and trans-1,2-cyclohexanediamine, cisand trans-1,4-cyclohexanediamine, methyl α-D-glucopyranoside, methyl β-D-glucopyranoside, and methyl α-D-mannopyranoside were of the highest commercial quality available and were used as received. Laser Flash Photolysis Studies. Time-resolved kinetic studies have been carried out by LFP employing a laser kinetic spectrometer using the third or the fourth harmonic (355 or 266 nm, respectively) of a Q-switched Nd:YAG laser, delivering pulses of 8 ns. The laser energy has been adjusted by the use of the appropriate filter to ≤10 mJ/pulse. A 3.5 mL quartz cell (Suprasil, 10 mm × 10 mm) was used, and all experiments have been carried out at T = 25 ± 0.5 °C under magnetic stirring. Experiments have been typically carried out employing 355 nm LFP on nitrogen-saturated acetonitrile or DMSO solutions containing 1.0 M dicumyl peroxide. Reactions of cyclohexanol have been also studied in isooctane, MBOH, methanol, and TFE. Because of the low solubility of dicumyl peroxide in TFE, of cisand trans-1,2-cyclohexanediol in acetonitrile solution containing 1.0 M dicumyl peroxide, and of methyl glycosides in acetonitrile and DMSO solutions containing 1.0 M dicumyl peroxide, the reactions of the cumyloxyl radical (CumO•) with cyclohexanol, cyclohexylamine, and triethylamine in TFE, with cis- and trans-1,2-cyclohexanediol in acetonitrile, and with the methyl glycosides in DMSO have been carried out employing 266 nm LFP on nitrogen-saturated solutions containing 10 mM dicumyl peroxide. The observed rate constants (kobs) have been obtained following the decay of the cumyloxyl radical (CumO•) absorption band between 490 and 520 nm as a function of the concentration of added substrate. Second-order rate constant (kH) for the reactions of CumO• with the substrates displayed in Chart 1 and with the methyl glycosides have been obtained from the slopes of the kobs versus [substrate] plots. The kH values displayed in Tables 1−3 are the average of at least two values obtained through independent experiments, with typical errors being ≤10%.

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00562. 5543

DOI: 10.1021/acs.joc.8b00562 J. Org. Chem. 2018, 83, 5539−5545

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The Journal of Organic Chemistry

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One chart showing substrates; additional text describing LFP studies; 21 figures showing plots of kobs versus substrate concentration for reactions of CumO• (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail [email protected]. ORCID

Michela Salamone: 0000-0003-3501-3496 Teo Martin: 0000-0003-4584-4322 Massimo Bietti: 0000-0001-5880-7614 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Professor Miquel Costas for helpful discussion and Professor Lorenzo Stella for the use of LFP equipment. REFERENCES

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Article

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via Strain Release: A Computational and Experimental Study. J. Org. Chem. 2013, 78, 4037−4048. (31) Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Morris, J. J.; Taylor, P. J. Hydrogen Bonding. Part 10. A Scale of Solute Hydrogenbond Basicity using log K Values for Complexation in Tetrachloromethane. J. Chem. Soc., Perkin Trans. 2 1990, 2, 521−529. (32) An even larger deactivation has been observed in the reaction of CumO• with triethylamine, where in TFE only an upper limit to kH could be determined: kH < 105 M−1·s−1. By considering that in acetonitrile kH = 2.1 × 108 M−1·s−1,16a with this substrate solvent hydrogen bonding leads to >3 orders of magnitude decrease in HAT reactivity [kH(MeCN)/kH(TFE) > 2100]. (33) Carey, F.; Sundberg, R. J. Advanced Organic Chemistry, Part B: Reactions and Synthesis, 5th ed.; Springer: 2007; DOI: 10.1007/978-0387-71481-3.

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