Remarkably Facile Solvolyses of Triflates via Carbocationic Processes

J. Org. Chem. , 2004, 69 (4), pp 1227–1234 ... 6-Methylbicyclo[3.1.0]hex-6-yl triflate (23), bicyclo[2.2.1hept-1-yl triflate (24), 1,6-methano[10]an...
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Remarkably Facile Solvolyses of Triflates via Carbocationic Processes in Dimethyl Sulfoxide Xavier Creary* and Elizabeth A. Burtch Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 [email protected] Received November 10, 2003

A number of triflates have been shown to undergo clean pseudo-first-order solvolysis reactions in DMSO-d6 to give products derived from carbocationic intermediates. Thus, t-BuCH(OTf)CO-t-Bu (5) and t-BuCH2OTf (9) react readily in DMSO-d6 at 25 °C to give a rearranged oxosulfonium salts, and subsequent alkene products where methyl migration to the incipient cationic center occurs. t-BuCH(OTf)CO2CH3 (14) gives analogous rearranged products, and 1-methylcyclopropyl triflate (21) gives a ring-opened allylic oxosulfonium salt. These triflates react primarily via k∆ pathways. 6-Methylbicyclo[3.1.0]hex-6-yl triflate (23), bicyclo[2.2.1hept-1-yl triflate (24), 1,6-methano[10]annulen-11-yl triflate (25), (CH3)2C(OTf)CO2CH3 (26), and (CH3)2CCN(OTf) (29) all react in DMSOd6 to give carbocation-derived products. PhCH(OTf)CF3 (33) and substituted analogues also react readily in DMSO-d6, and the Hammett F+ value is -3.7. This suggests a “borderline” mechanism where the transition state has substantial charge development. The primary feature of these solvolyses is the high reactivity of all of these triflates in DMSO-d6. Thus, these triflates are all more reactive in DMSO-d6 than in HOAc, and for most, rates are faster than in CF3CH2OH. Triflates 5, 21, 29, and 33 are 108-109 times more reactive in DMSO-d6 than the corresponding mesylates. It is suggested that the decreased need for electrophilic solvation of triflate anion, and the high cation solvating ability of DMSO, are the reasons for the high triflate reactivity in DMSO-d6. Introduction Dimethyl sulfoxide, 1 (DMSO), is a common solvent and reagent in organic chemistry.1 It is a relatively polar aprotic solvent, and SN2 and E2 reactions tend to occur more rapidly in this solvent than in protic solvents. We have recently reported that certain substrates also undergo facile solvolyses in DMSO-d6 to give products arising from carbocationic intermediates.2 Evidence for the involvement of cationic intermediates included the observation of a Hammett F+ value of -4.9 for reaction of 1 in DMSO-d6. Chloride 2 reacted in DMSO-d6 to give an indole product derived from a carbocation cyclization. Rates of reaction of chlorides 2 and 3 in DMSO-d6 are subject to a common ion rate suppression. The labeled trifluoroacetates 4 readily give products derived from a stepwise 1,2-elimination reaction in DMSO-d6 where the endo-trifluoroacetate group is lost along with the exohydrogen. The R-keto triflate 5 reacts readily in DMSOd6 to give rearranged products involving methyl migration. Finally, the mesylate 6 gives substitution products in DMSO-d6 which necessarily involve retention and, undoubtedly, formation of the 1-adamantyl cation. While solvolyses of these substrates occurred at room temperature or slightly above, the rate of reaction of triflate 5 in DMSO-d6 was noteworthy due to our previous (1) For reviews and leading references, see: (a) Buncel, E.; Wilson, H. Adv. Phys. Org. Chem. 1977, 14, 133. (b) Martin, D.; Weise, A.; Niclas, H.-J. Angew Chem., Int. Ed. Engl. 1967, 6, 318. (2) Creary, X.; Burtch, E.; Jiang, Z. J. Org. Chem. 2003, 68, 1117.

studies3 of this substrate in highly ionizing protic solvents such as trifluoroethanol, formic acid, and trifluoroacetic acid. The rate of reaction of 5 in DMSO-d6 was faster than in any other solvent studied. Over the years, we have studied the solvolytic chemistry of a number of triflates in polar protic solvents. We now report on the reaction of a variety of triflates in DMSO-d6 and a comparison of rates with those in the classic protic solvents acetic acid and trifluoroethanol which are commonly used in solvolysis reactions. Results and Discussion k∆ Substrates. The triflate 5 reacts readily in DMSOd6 at room temperature by a cationic process involving neighboring methyl participation to give exclusively rearranged products 7 and 8 (Scheme 1).2 We were (3) Creary, X.; McDonald, S. R. J. Org. Chem. 1985, 50, 474.

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J. Org. Chem. 2004, 69, 1227-1234

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Creary and Burtch SCHEME 1

therefore interested in the kinetic behavior of the related triflates 9 and 14. Neopentyl triflate 94 readily solvolyzes in DMSO-d6 at 25 °C by a pseudo-first-order process readily monitored by 19F NMR, where it is converted to a mixture of oxosulfonium ions 10 and 11 which are observable by 1H NMR spectroscopy. As the reaction progresses at 25 °C, the oxosulfonium ion 10 converts to the alkenes 12 and 13. Oxosulfonium ion 11 is, however, stable under the reaction conditions. The most remarkable feature is the rate of the reaction of triflate 9 in DMSO-d6 (Table 1). The rate is significantly faster than in the common solvents acetic acid and trifluoroethanol and comparable to that in the highly ionizing solvent formic acid. These results are consistent with solvolysis of neopentyl triflate in DMSO-d6 mainly via a k∆ process involving methyl migration. Capture of the rearranged cation by DMSO-d6 gives the major product 10, while proton loss from the rearranged carbocation (or elimination from 10) leads to the alkene products 12 and 13. Competing with this cation-forming k∆ process is a small amount of the ks process which leads to the 9% unrearranged product 11. Previous solvolytic studies on triflate 9 in protic solvents gave only rearranged products.4 The formation of unrearranged 11 attests to the relatively high nucleophilicity of DMSO-d6 even though carbocation formation in DMSO-d6 is quite facile. The reaction of ester 14 in DMSO-d6 follows a similar course, although a slightly elevated temperature is needed (40-60 °C) so that reaction occurs at a convenient rate. As in the case of 9, the major product is the rearranged elimination product, the alkene 15, while a smaller amount of the rearranged isomeric alkene 16 is also formed (Scheme 2). Also formed are significant amounts of unrearranged products 17 and 18. Careful (4) Shiner, V. J., Jr.; Seib, R. C. Tetrahedron Lett. 1979, 123.

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monitoring of the reaction before completion by NMR reveals the buildup of oxosulfonium ion 19, which is subsequently converted to 17 and 18. We have previously shown2 that oxosulfonium ions can react with traces of water in DMSO-d6 to give alcohol products. The oxidized product 18 comes from competing elimination of (CD3)2S from 19 (Kornblum oxidation).5 Small amounts of the rearranged oxosulfonium ion 20 can also be detected, but it subsequently converts to 15 and 16 under the reaction contitions. As in the case of triflates 5 and 9, the solvolysis of 14 in DMSO-d6 is remarkably facile relative to other solvents, and the rate of 14 in DMSO-d6 even exceeds that in formic acid. The triflate 21 (a k∆ substrate)6 has also been studied at room temperature in DMSO-d6, where the oxosulfonium ion 22 (stable under the reaction conditions) is the exclusive product. This ring-opened product is consistent with a cationic process where we assume that, as in the case of other solvents, the ring opening is concerted with ionization. As before, the rate of reaction in DMSO-d6 exceeds that in highly ionizing protic solvents.

kC Substrates. To shed further light on the high reactivity of triflates in DMSO-d6, attention was next turned to a series of triflates that cannot react via the (5) (a) Kornblum, N.; Powers, J. W.; Anderson, G. J.; Jones, W. J.; Larson, H. O.; Weaver, W. M. J. Am. Chem. Soc. 1957, 79, 6562. (b) Kornblum, N.; Jones, W. J.; Anderson, G. J. J. Am. Chem. Soc. 1959, 81, 4113. (c) Johnson, A. P.; Pelter, A. J. Chem. Soc. 1964, 520. (6) Creary, X. J. Org. Chem. 1976, 41, 3734.

Facile Solvolyses of Triflates TABLE 1. Solvolysis Rates in Various Solvents solvent

T (°C)

k (s-1)

DMSO-d6 50% DMSO-d6b 25% DMSO-d6b 15% DMSO-d6b HOAc CF3CH2OH HCO2H DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 HOAc CF3CH2OH HCO2H DMSO-d6 HOAc CF3CH2OH HCO2H DMSO-d6 HOAc CF3CH2OH HCO2H DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 HOAc CF3CH2OH DMSO-d6 HOAc CF3CH2OH DMSO-d6 HOAc CF3CH2OH DMSO-d6 HOAc CF3CH2OH DMSO-d6 15% DMSO-d6b HOAc CF3CH2OH DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 HOAc CF3CH2OH DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 DMSO-d6 HOAc CF3CH2OH

25.0 25.0 25.0 25.0 25.0 25.0 25.0 155.0 130.0 25.0a 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 140.0 130.0 115.0 25.0a 25.0 25.0 25.0 100.0 100.0 100.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 100.0 75.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 25.0 155.0 130.0 25.0a 25.0 25.0a 25.0a

1.05 × 10-3 5.60 × 10-5 6.23 × 10-6 1.94 × 10-6 4.15 × 10-6 4.36 × 10-5 2.22 × 10-4 2.10 × 10-5 1.90 × 10-6 1.00 × 10-12 1.23 × 10-3 5.65 × 10-6 1.11 × 10-4 1.36 × 10-3 3.50 × 10-6 1.05 × 10-8 1.75 × 10-7 1.58 × 10-6 7.66 × 10-3 5.52 × 10-5 9.24 × 10-4 5.07 × 10-3 4.41 × 10-5 1.73 × 10-5 3.81 × 10-6 1.96 × 10-11 5.08 × 10-3 5.82 × 10-5 5.47 × 10-3 1.59 × 10-5 1.98 × 10-6 6.17 × 10-5 5.83 × 10-6 3.11 × 10-7 4.89 × 10-4 too fast to measure 6.07 × 10-4 3.19 × 10-3 too fast to measure 9.12 × 10-4 5.25 × 10-5 3.85 × 10-5 2.43 × 10-5 1.85 × 10-6 2.99 × 10-9 5.78 × 10-3 5.54 × 10-6 c 1.44 × 10-3 c 1.41 × 10-2 7.88 × 10-5 3.89 × 10-5 1.84 × 10-4 8.33 × 10-6 1.00 × 10-6 3.04 × 10-12 6.97 × 10-4 2.28 × 10-8 8.31 × 10-10

substrate t-BuCH(OTf)CO-t-Bu 5

t-BuCH(OMs)CO-t-Bu 44 t-BuCH2OTf 9

t-BuCH(OTf)CO2CH3 14

1-methylcyclopropyl triflate 21

1-methylcyclopropyl mesylate 45

6-methylbicyclo[3.1.0]hex-6-yl triflate 23 bicyclo[2.2.1hept-1-yl triflate24 1,6-methano[10]annulen-11-yl triflate 25 (CH3)2C(OTf)CO2CH3 26 (CH3)2CCN(OTf) 29

(CH3)2CCN(OMs) 46 PhCH(OTf)CF3 33 m-CH3C6H4CH(OTf)CF3 34 m-CF3C6H4CH(OTf)CF3 35 p-CF3C6H4CH(OTf)CF3 36 p-COCH3C6H4CH(OTf)CF3 37 PhCH(OMs)CF3 47 CH3CH(OTf)PO(OEt)2 43

a

Extrapolated from data at other temperatures. b The other solvent was CDCl3. c Reference 11a.

k∆ route. The triflates 236 and 247 have been previously studied in polar protic solvents, and they react via solvent-unassisted pathways to generate carbocationic intermediates. We have recently prepared the bicyclic triflate 25,8 and it too reacts via a solvent-unassisted process in polar protic solvents. Table 1 shows rate data for reaction of these kC substrates in DMSO-d6 and, for (7) Bingham, R. C.; Sliwinski, W. F.; Schleyer, P. v. R. J. Am. Chem. Soc. 1970, 92, 3471. (8) Creary, X.; Miller, K. J. Org. Chem. 2003, 68, 8683.

comparison purposes, rate data for solvolyses in acetic acid and trifluoroethanol. These substrates are all more reactive in DMSO-d6 than in acetic acid, but trifluoroethanol solvolysis rates are comparable to (in the case of 23) or faster than DMSO-d6 rates (in the case of 24 and 25). The reduced importance of DMSO nucleophilicity appears to a factor in the decreased reactivity of 24 and 25 in DMSO-d6, yet these substrates continue to show quite high reactivity in DMSO-d6 despite the fact that the developing cationic intermediates cannot be efJ. Org. Chem, Vol. 69, No. 4, 2004 1229

Creary and Burtch SCHEME 2

SCHEME 3

fectively nucleophilically solvated from the rear of the departing leaving group.

The triflate 26 can be prepared, and it is a very reactive substrate at 25 °C in acetic acid (half-life ) 19 min) and trifluoroethanol (half-life ) 3.6 min). Previously, the analogous mesylate derivative was studied in protic solvents, and a cationic intermediate was implicated in these solvolyses.9 In similar fashion, the triflate 29 was (9) Creary, X.J. Am. Chem. Soc. 1984, 106, 5568.

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also suggested to react via a cationic mechanism in protic solvents.10,11b These so-called “electron-deficient” cationic intermediates underwent mainly proton loss to give elimination products. With these precedents in mind, the triflates 26 and 29 were mixed with DMSO-d6 where reactions occur quite readily. The triflate 26 gave the oxosulfonium salt 27 which was stable at 25 °C but converted to the alcohol 28 on heating to 80 °C (Scheme 3). The triflate 29 also gave an analogous oxosulfonium salt 30, along with methacrylonitrile, 31. However, 30 was not stable at 25 °C, but converted to the cyanohydrin 32 and the alkene 31 at this temperature. The reactions of these triflates in DMSO-d6 are complete before NMR spectra can be recorded. Attempts to (10) Gassman, P. G.; Talley, J. J. J. Am. Chem. Soc. 1980, 102, 1214. (11) (a) Allen, A. D.; Ambridge, I. C.; Che, C.; Micheal, H.; Muir, R. J.; Tidwell. T. T. J. Am. Chem. Soc. 1983, 105, 2343. (b) Gassman, P. G.; Tidwell, T. T. Acc. Chem. Res. 1983, 16, 279.

Facile Solvolyses of Triflates

FIGURE 1. Plot of log k for reaction of ArCH(OTF)CF3 in DMSO-d6 vs σ+ values.

detect unreacted 26 and 29 by quenching the reaction in CDCl3 (an unreactive solvent) within 5 s of mixing showed complete reaction of these triflates. Hence, rates of 26 and 29 are much too fast to be measured by conventional techniques. They are substantially more reactive in DMSO-d6 than in acetic acid or trifluoroethanol. The nucleophilicity/basicity of DMSO therefore appears to have a role in the rates of reaction of triflates 26 and 29. ArCHCF3OTf Systems: Borderline Substrates in DMSO-d6. Extensive solvolytic studies have been carried out on trifluoromethyl-substituted substrates of the type R2CCF3(OSO2R).11 These substrates react in polar protic solvents to give products derived from carbocationic intermediates that are destabilized by the electronwithdrawing CF3 group. We have now examined triflate 33 and substituted analogues 34-37 in DMSO-d6. These substrates all react readily at room temperature to give the oxosulfonium ions 38 which can readily be observed spectroscopically. These oxosulfonium ions are not stable at room temperature but convert to mixtures of alcohols 39 and ketones 40. Furthermore, ketones 40 are not stable under the reaction conditions, but react with water in the DMSO-d6 to form hydrates 41.12 Data in Table 1 show that 33 (Ar ) Ph) is significantly more reactive in DMSO-d6 than in acetic acid or in CF3CH2OH. A substituent effect study on rate was therefore carried out on ArCHCF3OTf as a probe for charge (12) (a) Stewart, R.; Van Dyke, J. D. Can. J. Chem. 1970, 48, 3961. (b) Ritchie, C. D. J. Am. Chem. Soc. 1984, 106, 7187.

development in the transition state. Previously,11 Tidwell had determined solvent dependent F+ values of -7 to -11 for solvolyses of ArCHCF3OTs in polar protic solvents, and this corresponds to a transition state with significant charge development and a very large demand for stabilization of the developing positive charge. By way of contrast, the F+ value (Figure 1) for reaction of ArCHCF3OTf in DMSO-d6 is only -3.7, a value that is significantly smaller than the value in polar protic solvents. We conclude that there is still substantial charge development in the transition state 42 for formation of oxosulfonium ion 38. However, the cations [ArCHCF3]+ may not be a discrete intermediates in the region where aryl substituents are electron-withdrawing. Nucleophilicity of DMSO-d6 may be decreasing the lifetime of the potential carbocation intermediate to the point where the reaction is an enforced Sn2 reaction,13 but with a transition state 42 still possessing significant charge development. J. Org. Chem, Vol. 69, No. 4, 2004 1231

Creary and Burtch CHART 1.

CH3CH(OTf)PO(OEt)2. A ks Substrate. The ks mechanism lies at the other end of the solvolysis spectrum and represents a process where there is little cationic character in the transition state for solvolysis.14 We have previously studied the triflate 43 in a variety of protic solvents and found that in solvents such as ethanol and acetic acid, 43 is a ks substrate.15 Isotope effect studies implicate a transition state with little cationic character in ethanol, while the degree of cationic character increases in (CF3)2CHOH, a solvent known to promote carbocation formation. Triflate 43 has now been reacted in DMSO-d6, where rapid reaction occurs at 25 °C (halflife ) 16 min) to give the oxosulfonium ion 44 as the exclusive product. A kinetic isotope effect study (k(43)/ k(43-d4) ) 1.08 in DMSO-d6) indicates little transition state charge development in the DMSO solvolysis. The oxosulfonium ion 44 is relatively stable at room temperature, but over a few days it reacts with the trace of water present in the DMSO-d6 to give the alcohol 45. Addition of 2,6-lutidine to the salt 44 in DMSO-d6 results in a base-catalyzed conversion to a mixture of alcohol 45 and the ketophosphonate CH3COPO(OEt)2 over a period of a few hours.

The DMSO-d6/HOAc Rate Ratio. The DMSO-d6/CH3CO2H rate ratio can be used as a measure of the importance of DMSO nucleophilicity in the solvolysis of triflates. Large values (∼104) indicate that the nucleophilic character DMSO is quite important in the solvolysis. This is illustrated in the case of triflate 43, which is undoubtedly a ks substrate in DMSO. The DMSO-d6/CH3CO2H ratio decreases as the transition state for solvolysis (13) (a) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161. (b) Richard, J. P.; Jencks, W. P. J. Am. Chem. Soc. 1982, 104, 4689. (c) Richard, J. P.; Jencks, W. P. J. Am. Chem. Soc. 1984, 106, 1383. (d) Richard, J. P. In Advances in Carbocation Chemistry; Creary, X., Ed.; JAI Press Inc.; Greenwich, CT, 1989; Vol. 1, p 121. (14) For a discussion of the spectrum of solvolysis mechanisms, see: (a) Allen, A. D.; Kanagasabapathy, V. M.; Tidwell, T. T. J. Am. Chem. Soc. 1985, 107, 4513. (b) Richard, J. P.; Jencks, W. P. J. Am. Chem. Soc. 1984, 106, 1383. (c) Bentley, T. W.; Schleyer, P. v. R. Adv. Phys. Org. Chem. 1977, 14, 1. (d) Sneen, R. A. Acc. Chem. Res. 1973, 6, 46. (15) Creary, X.; Underiner, T. L. J. Org. Chem. 1985, 50, 2165.

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Triflate/Tosylate Rate Ratios (kOTf/kOTs)

becomes more cationic in character as in the borderline substrate 33. This is indicative of the decreasing importance of solvent nucleophilicity in this substrate. Finally, the smallest DMSO-d6/CH3CO2H rate ratios are seen in the kC substrates 24 and 25. Smaller values indicate that the relatively nucleophilic DMSO-d6 solvent is less effective at solvating the developing cationic intermediate. However, triflates 24 and 25 are still more reactive in DMSO-d6 than in acetic acid. This suggests that reorganization of DMSO-d6 to form a solvent shell in the vicinity a developing carbocation can still be quite effective despite the fact that direct backside solvation is precluded. This suggestion (facile reorganization of DMSOd6 to form a solvent shell) also accounts for the rapid reaction of k∆ substrates in DMSO-d6 even though direct nucleophilic solvent involvement is not important.

The Triflate/Mesylate Rate Ratio. The triflate leaving group has always been recognized as possessing relatively high nucleofugality (Chart 1).16 Previously, triflate/tosylate rate ratios of ∼104-105 have been seen for solvolytic reactions in protic solvents.10,16 Typical examples include methyl and ethyl triflate which react via ks processes in acetic acid at rates of 104.3 and 104.5 times faster that the corresponding tosylates. Cyclopropyl derivatives react via k∆ processes and triflate/tosylate rate ratios in acetic acid are again in the range of 105. In trifluoroethanol, the triflate/tosylate rate ratio for the R-cyano derivative 29 is also approximately 105. This high nucleofugality of triflate vs tosylate is attributed to the stability of the triflate anion due to the electronwithdrawing CF3 group. That the reactivity of the triflates described in this paper in DMSO-d6 is indeed remarkable has been verified by examination of the triflate/mesylate rate ratio18 for triflates 5, 21, 29, and 33 (and the mesylate analogues (16) (a) Streitweiser, A., Jr.; Wilkins, C. L.; Kiehlmann, E. J. Am. Chem. Soc. 1968, 90, 1598. (b) Su, T. M.; Sliwinski, W. F.; Schleyer, P. v. R. J. Am. Chem. Soc. 1969, 91, 5386. (17) Schleyer, P. v. R.; Sliwinski, W. F.; Van Dine, G. W.; Scho¨llkopf, U.; Paust, J.; Fellenberger, K. J. Am. Chem. Soc. 1972, 94, 125. (18) Mesylates and triflates have comparable reactivity. See: Noyce, D. S.; Virgilio, J. A. J. Org. Chem. 1972, 37, 2643.

Facile Solvolyses of Triflates CHART 2. Triflate/Mesylate Rate Ratios (kOTf/ kOMs) in DMSO-d6

does the triflate leaving group. Therefore, DMSO-d6 is a very reasonable solvent for cationic processes involving triflates even though this solvent cannot be a hydrogen bond donor.

Experimental Section

44-47) in this solvent (Chart 2). While triflate 5 solvolyzes in DMSO-d6 with a half-life of 11 min at 25 °C, the corresponding mesylate t-BuCH(OMs)CO-t-Bu (44) has a half-life of 10 h at 155 °C. This remarkable reactivity difference corresponds to an extrapolated triflate/mesylate rate ratio of 1 × 109 at 25 °C. Comparable values can be extrapolated for the triflates 21 and 33 the corresponding mesylates. A fourth example of this remarkable triflate/mesylate rate ratio in DMSO-d6 comes from examination of triflate 29 and its mesylate analogue (CH3)2CCN(OMs) (46). The mesylate 46 is quite unreactive in DMSO-d6, but it does react at 100 °C with a half-life of 7.9 h (Table 1). Data in Table 1 allow the determination of an extrapolated rate constant of 2.99 × 10-9 s-1 at 25 °C. By way of contrast, the triflate 29 reacts completely in DMSO-d6 before spectra can be recorded. However, diluting the DMSOd6 with CDCl3 reduces the reactivity of triflates and 29 reacts with a half-life of 12.7 min at 25 °C in 15% DMSOd6/85% CDCl3. If one assumes that the reactivity of triflate 29 in mixed DMSO-d6/CDCl3 systems parallels that of triflate 5 (which is 557 times faster in pure DMSO-d6 than in 15% DMSO-d6), then the estimated half-life of triflate 29 in pure DMSO-d6 is 1 s. This corresponds to a triflate/mesylate rate ratio of about 2 × 108. These unusually high triflate/mesylate solvolysis rate ratios (108 to 109) in DMSO-d6 suggest that solvolysis reactions involving carbocations require electrophilic as well as nucleophilic solvation and DMSO-d6 is a very good nucleophilic solvator of developing carbocations. However, with the triflate leaving group, electrophilic solvation of the developing triflate anion is not as important as solvation of anions such as mesylate. Hence, triflates have enhanced reactivity. Conclusions. Certain triflates undergo very facile solvolysis reactions when dissolved in DMSO-d6 giving both rearranged and unrearranged products. Mechanisms involve k∆ processes (which give carbocation rearrangements), kC processes, ks processes, as well as “borderline” processes. The entire spectrum of carbocation reactivity is therefore available to triflates in DMSO-d6. The most remarkable feature of these reactions is the high reactivity that triflates show in DMSO-d6. Certain triflates give carbocation chemistry in DMSO-d6 at rates that exceed those in the “traditional” highly ionizing protic solvents trifluoroethanol and formic acid. Rates of triflates can exceed that of analogous mesylates by factors of 108-109. It is suggested that the mesylate leaving group requires much more electrophilic solvation than

Preparation of Triflates. The preparations of triflates 5,19 9,4 21,6 23,6 24,7 25,8 29,10 33,11a and 3915 have previously been described, as has the preparation of t-BuCH(OMs)CO-t-Bu (44).20 Preparation of t-BuCH(OTf)CO2CH3 (14). A solution of 327 mg of methyl 2-hydroxy-3,3-dimethylbutanoate21 and 379 mg of 2,6-lutidine in 4 mL of methylene chloride was cooled to -20 °C, and 1.23 g of triflic anhydride was added dropwise. The mixture was stirred at -20 °C for 25 min and was then warmed to room temperature. The mixture was then transferred to a separatory funnel with ether and rapidly washed with cold water, dilute HCl, and saturated NaCl solution. After drying over a mixture of Na2SO4 and MgSO4, the solids were removed by filtration and the solvent was removed using a rotary evaporator. Distillation of the residue gave 351 mg (56%) of triflate 14: bp 29-30 °C (0.08 mm); 1H NMR of 14 (CDCl3) δ 4.78 (s, 1 H), 3.84 (s, 3 H), 1.09 (s, 9 H); 13C NMR of 14 (CDCl3) δ 166.7, 118.5 (q, J ) 319 Hz), 90.8, 52.7, 35.0, 25.7; exact mass (EI) calcd for C8H14F3O5S 279.0514, found 279.0539. Preparation of 1-Methylcyclopropyl Mesylate (45). A solution of 275 mg of 1-methylcyclopropanol22 and 775 mg of mesyl chloride in 4 mL of methylene chloride was cooled to -10 °C, and 816 mg of Et3N in 1 mL of methylene chloride was added dropwise. The mixture was warmed to room temperature and then transferred to a separatory funnel using ether and water. The ether extract was washed with water, dilute hydrochloric acid, dilute NaOH solution, and saturated NaCl solution and dried over MgSO4. After filtration, the solvents were removed using a rotary evaporator, and the residue was distilled to give 442 mg (77% yield) of mesylate 45: bp 42 °C (0.05 mm); 1H NMR (CDCl3) δ 3.00 (s, 3 H), 1.70 (s, 3 H), 1.26 (m, 2 H), 0.70 (m, 2 H); 13C NMR (CDCl3) δ 60.2, 39.9, 22.6, 12.8; exact mass (EI) calcd for C5H10O3S 150.0351, found 150.0357. Preparation of (CH3)2CCN(OMs) (46). A solution of 410 mg of acetone cyanohydrin and 805 mg of mesyl chloride in 4 mL of methylene chloride was cooled to -10 °C, and 808 mg of Et3N in 1.0 mL of methylene chloride was added dropwise. The mixture was warmed to room temperature and then transferred to a separatory funnel using ether and water. The ether extract was washed water, dilute hydrochloric acid, dilute NaOH solution, and saturated NaCl solution and dried over MgSO4. After filtration, the solvents were removed using a rotary evaporator to give 584 mg (74% yield) of mesylate 46, which was used for kinetic studies without further purification: 1H NMR (CDCl3) δ 3.19 (s, 3 H), 1.91 (s, 6 H). 13 C NMR (CDCl3) δ 118.2, 75.1, 40.2, 28.4; exact mass (EI) calcd for C4H6NO3S 148.0069, found 148.0068. (M - CH3 peak. There is no observable molecular ion.) Preparation of PhCH(OMs)CF3 (47). A solution of 130 mg of R-(trifluoromethyl)benzyl alcohol and 122 mg of mesyl chloride in 2 mL of methylene chloride was cooled to -10 °C, and 122 mg of Et3N in 0.5 mL of methylene chloride was added dropwise. The mixture was warmed to 0 °C and then transferred to a separatory funnel using ether and water. The ether extract was washed with dilute hydrochloric acid and saturated NaCl solution and dried over MgSO4. After filtration, (19) Creary, X. J. Org. Chem. 1979, 44, 3938. (20) Creary, X. J. Org. Chem. 1980, 45, 2419. (21) Bessard, Y.; Crettaz, R. Tetrahedron 2000, 56, 4739. (22) (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A. Synthesis 1991, 234. (b) DePuy, C. H.; Dappen, G. M.; Eilers, K. L.; Klein, R. A. J. Org. Chem. 1964, 29, 2813.

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Creary and Burtch the solvents were removed using a rotary evaporator, and the residue was distilled to give 147 mg (78% yield) of mesylate 47: bp 90 °C (0.05 mm); 1H NMR (CDCl3) δ 7.53-7.43 (m, 5 H), 5.78 (q, J ) 6.5 Hz, 1 H), 2.96 (s, 3 H); 13C NMR (CDCl3) δ 130.8, 129.7, 129.1, 128.1, 122.3 (q, J ) 281 Hz), 79.2 (q, J ) 35 Hz), 39.4; exact mass (EI) calcd for C9H9F3O3S 254.0225, found 254.0238. Preparation of p-CF3C6H4CH(OTf)CF3 (36). A solution of 108 mg of p-CF3C6H4CH(OH)CF3 (prepared by LiAlH4 reduction of p-CF3C6H4COCF3)23 and 91 mg of 2,6-lutidine in 2 mL of methylene chloride was cooled to -20 °C, and 218 mg of triflic anhydride was added dropwise. The mixture was stirred at -20 °C for 25 min and was then warmed to room temperature. The mixture was then transferred to a separatory funnel with ether and then rapidly washed with cold water, dilute HCl, and saturated NaCl solution. After the mixture was dried over a mixture of Na2SO4 and MgSO4 and filtered, the solvent was removed using a rotary evaporator. Distillation of the residue gave 70 mg (42%) of triflate 36: bp 70 °C (3 mm); 1H NMR (CDCl3) δ 7.76 and 7.66 (AA′BB′ quartet, 4 H), 5.91 (q, J ) 5.7 Hz, 1 H). 13C NMR (CDCl3) δ 133.7 (q, J ) 33 Hz), 131.9, 128.4, 126.4 (q, J ) 3.7 Hz), 123.4 (q, J ) 272 Hz), 121.2 (q, J ) 281 Hz), 118.2 (q, J ) 320 Hz), 81.4 (q, J ) 36 Hz); exact mass (EI) calcd for C10H5F9O3S 375.9816, found 375.9825. The triflates m-CH3C6H4CH(OTf)CF3 (34), m-CF3C6H4CH(OTf)CF3 (35), and p-COCH3C6H4CH(OTf)CF3 (37) were prepared by completely analogous procedures. Solvolysis of Triflates in DMSO-d6. Kinetics Procedures. Rates of reaction of triflates and mesylates were determined by various 19F and 1H NMR methods. Method 1.24 Approximately 5 mg of the appropriate triflate was dissolved in 1 mL of DMSO-d6, and the sample was sealed in an NMR tube. The tube was placed in a constant-temperature bath at the appropriate temperature or in the probe of the NMR spectrometer at 25.0 °C. At appropriate time intervals, the NMR tube was analyzed by 19F NMR and the relative areas of unreacted triflate and triflate anion were determined. First-order rate constants were calculated by standard least squares procedures. Correlation coefficients were all greater than 0.9995. Rates of 5, 24, 25, 35-37, 43, and 43-d4 were measured by this method. Method 2. Approximately 30 mg of the appropriate triflate was rapidly dissolved in 3 mL of DMSO-d6 at 25 °C. At appropriate times, approximately 0.4 mL of the DMSO-d6 solution was quenched in 3 mL of CDCl3 at 0 °C. The CDCl3 solutions were rapidly analyzed by 19F NMR for unreacted triflate and triflate anion. Rates of 21, 23, 33, and 34 were measured by this method. In the case of triflate 21, the analysis was by 600 MHz 1H NMR. Method 3. Approximately 5 mg of the appropriate triflate or mesylate was dissolved in 1 mL of DMSO-d6, and a portion of the solution was sealed in an NMR tube. The tube was placed in a constant-temperature bath at the appropriate temperature or in the probe of the NMR at 25.0 °C. At appropriate time intervals, the tube was analyzed by 600 MHz (23) Creary, X. J. Org. Chem. 1987, 52, 5026. (24) Creary, X.; Wang, Y.-X. J. Org. Chem. 1992, 57, 4761.

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1H NMR and areas due to starting triflate or mesylate and products were measured. Rates of 9, t-BuCH(OMs)CO-t-Bu (44), 1-methylcyclopropyl mesylate (45), (CH3)2CCN(OMs) (46), and PhCH(OMs)CF3 (47) were measured by this method. Method 4.25 Approximately 5 mg of the appropriate triflate was dissolved in 1 mL of 0.06 M 2,6-lutidine in DMSO-d6, and the sample was sealed in an NMR tube. The tube was placed in a constant-temperature bath at the appropriate temperature or in the probe of the NMR at 25.0 °C. At appropriate time intervals, the tube was analyzed by 1H NMR and the shift of the upfield singlet due to the 2,6-lutidine was determined. The shift of the 2,6-lutidine, which moves downfield as a function of time, was monitored. After 10 half-lives a final reading was taken. First-order rate constants were calculated by standard least-squares procedures. Rates of 14 were measured by this method. Rates of solvolyses of triflates in HOAc, CF3CH2OH, HCO2H, and mixed DMSO-d6/CDCl3 solvents were determined using 19F and 1H NMR methods analogous to those described above. Solvolysis of Triflates in DMSO-d6. Product Studies. Approximately 5-10 mg of the appropriate triflate was dissolved in 1 mL of DMSO-d6, and a portion of the solution was placed in an NMR tube. The reaction was periodically monitored by 600 MHz 1H NMR spectroscopy. Neutral products were all identified by spectral comparison with authentic samples in DMSO-d6. 1H NMR spectra of both stable and unstable oxosulfonium ions are given in the schemes. Product ratios were determined by integration of the appropriate signals in the 1H NMR spectra. The oxosulfonium ions 10, 19, 20, 30, and 38 were not stable under the reaction conditions and were converted to the products shown in the schemes. The 1H NMR spectral data given in the schemes were obtained in situ as the reactions progressed. Typical NMR spectral data acquired during the solvolyses of triflates 9 and 33 (Ar ) Ph), which show unstable oxosulfonium ions 10 and 38 (Ar ) Ph), are presented as Supporting Information. The oxosulfonium ion 11 was stable under the reaction conditions. However, 13C NMR data were not obtained since 11 was formed in 9% yield. Oxosulfonium ions 22 and 44 were stable enough under the reaction conditions to permit recording of 13C NMR spectra: 13C NMR of 22 (DMSO-d6) δ 138.9, 117.2, 78.6, 18.9; 13C NMR of 44 (DMSO-d6) δ 77.5 (d, JC-P ) 165 Hz), 63.21 (d, JC-P ) 6.7 Hz), 63.17 (d, JC-P ) 6.7 Hz), 16.3 (d, JC-P ) 4.8 Hz), 15.8.

Acknowledgment is made to the National Science Foundation for partial support of this research. Supporting Information Available: 1H and 13C NMR spectra of compounds 14, 36, and 45-47, as well as evolving 1H NMR spectra during reaction of triflate 9 and evolving 19F NMR spectra during reaction of triflate 33. This material is available free of charge via the Internet at http://pubs.acs.org. JO0356558 (25) Creary, X.; Jiang, Z. J. Org. Chem. 1994, 59, 5106.