DOI: 10.1002/chem.201403161
Full Paper
& Ambident Reactivity
Di- and Triarylmethylium Ions as Probes for the Ambident Reactivities of Carbanions Derived from 5-Benzylated Meldrum’s Acid Xi Chen, Yue Tan, Guillaume Berionni, Armin R. Ofial,* and Herbert Mayr[a] Dedicated to Professor Hans-Ulrich Reißig on the occasion of his 65th birthday
Abstract: The kinetics of the reactions of carbocations with carbanions 1 derived from 5-benzyl-substituted Meldrum’s acids 1-H (Meldrum’s acid = 2,2-dimethyl-1,3-dioxane-4,6dione) were investigated by UV/Vis spectroscopic methods. Benzhydryl cations Ar2CH + added exclusively to C-5 of the Meldrum’s acid moiety. As the second-order rate constants (kC) of these reactions in DMSO followed the linear freeenergy relationship lg k = sN(N+E), the nucleophile-specific
reactivity parameters N and sN for the carbanions 1 could be determined. In contrast, trityl cations Ar3C + reacted differently. While tritylium ions of low electrophilicity (E < 2) reacted with 1 through rate-determining b-hydride abstraction, more Lewis acidic tritylium ions initially reacted at the carbonyl oxygen of 1 to form trityl enolates, which subsequently reionized and eventually yielded triarylmethanes and 5-benzylidene Meldrum’s acids by hydride transfer.
Introduction
of the alkylation reactions were mostly interpreted on the basis of the principle of hard and soft acids and bases (HSAB principle),[21] which predicts O-alkylation with hard and C-alkylation with soft electrophiles. Because the HSAB principle neither differentiates between kinetic and thermodynamic control nor considers the diffusion limit, it often fails to predict the correct regioselectivity.[22] An alternative treatment of ambident reactivity based on Marcus theory has, therefore, been proposed and applied to reactions of enolate ions.[23] A third reaction channel exists for enolate ions that carry hydrogen atoms in b-position to the carbonyl group. As described for several examples, such enolates may react with carbocations or Michael acceptors by b-hydride transfer to give olefins.[24] We now report that carbanions derived from 5-benzylated Meldrum’s acid (1)[25, 26] react with carbocations through all three mentioned paths (Scheme 1), which makes kinetic studies of their reactivity rather challenging. By using benzhydrylium ions and tritylium ions as electrophilic probes it has been possible to investigate independently the rates of CC bond formation and hydride transfer of Meldrum’s acid derived carbanions 1 and to assign reactivity parameters N and sN to the different positions. A set of benzhydrylium ions, Ar2CH + , served as reference electrophiles[27] for the determination of the carbon reactivity of 1. Tritylium ions (Ar3C + ) are sterically more demanding and cannot react with C-5 of the Meldrum’s acid moiety of 1. Yet, they have recently been shown to act as reliable reference electrophiles for the determination of hydride donating abilities of several types of hydride donors,[28] which made them promising candidates to study the hydride transfer rates of carbanions 1. Both types of carbocations may alternatively attack
Carbonyl-substituted carbanions (enolates) or related organometallic species are usually generated with the aim to make use of their reactivity at carbon, for example, for CC bond forming reactions.[1] In order to quantify the nucleophilic carbon reactivity of enolate anions, we have previously investigated the kinetics of their reactions with benzhydrylium ions (Ar2CH + ) and structurally related quinone methides. Analysis of the second-order rate constants (k) of these reactions by the correlation Equation (1),[2–6] in which E describes the reactivity of the reference electrophiles, provided the nucleophile-specific, solvent-dependent nucleophilicity parameters N (and sensitivities sN) for enolates and other types of acceptor-stabilized carbanions in DMSO,[7–17] water,[9, 10] and methanolic solutions.[11, 18] lg k 20 o C ¼ sN ðN þ EÞ
ð1Þ
As ambident nucleophiles, enolates can alternatively undergo O-alkylation with formation of enol ethers, a reaction course that is frequently used for the protection of carbonyl groups.[19] The site of attack depends on the structure of the enolate as well as on the nature of the electrophile, the solvent, and the counterion.[20] In the past, the regioselectivities [a] Dr. X. Chen,+ Dr. Y. Tan,+ Dr. G. Berionni, Dr. A. R. Ofial, Prof. Dr. H. Mayr Department Chemie, Ludwig-Maximilians-Universitt Mnchen Butenandtstr. 5–13, 81377 Mnchen (Germany) E-mail: [email protected] [+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403161. Chem. Eur. J. 2014, 20, 1 – 10
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Full Paper Table 1. Benzhydrylium ions (Ar2CH + ) 3 used as reference electrophiles in this work and their electrophilicity parameters, E. E[a]
Ar2CH +
(lil)2CH + (3 a)
10.04
(jul)2CH + (3 b)
9.45
(ind)2CH + (3 c)
8.76
(thq)2CH + (3 d)
8.22
(pyr)2CH + (3 e)
7.69
(dma)2CH + (3 f)
7.02
+
Scheme 1. Possible reactivities of carbanions 1 towards carbocations R .
at oxygen to give enol ethers, which was only observable when tritylium ions of high Lewis acidity were employed.
Results and Discussion Synthesis of potassium salts 1K
(ani)2CH + (3 g)
Knoevenagel condensations of substituted benzaldehydes with Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione)[29] and reduction of the resulting benzylidene Meldrum’s acids 2 a– e with sodium borohydride followed by acidic work-up generated the carbanion precursors 1-H (Scheme 2).[30] Subsequent treatment of the 5-arylmethyl-2,2-dimethyl-1,3-dioxane-4,6diones (1 a–e)-H with equimolar amounts of potassium tertbutoxide in ethanol gave rise to the precipitation of the potassium salts (1 a–e)-K, which were collected by filtration and characterized by NMR spectroscopy.
0.00
[a] From ref. [27].
Scheme 3. Products from CC bond-forming reactions of carbanion 1 a with the benzhydrylium tetrafluoroborates 3 d-BF4 (in DMSO) and 3 f-BF4 (in MeCN); yields of products after crystallization.
from ethyl acetate gave crystals of 4 af that were suitable for single crystal X-ray analysis (Figure 1) and provided unequivocal evidence for the CC bond formation between carbocation 3 f and carbanion 1 a.[31] The long C3C16 bond (158.2(2) pm) can be explained by steric strain and incipient heterolysis of this CC bond though the NMR spectroscopy data do not provide clear evidence for this effect. Attack at C-5 was also observed in the reaction of the ambident nucleophile 1 c-K with the bis(p-anisyl)methylium ion 3 g, which is by a factor of > 107 more electrophilic than 3 d or 3 f (Scheme 4). The NMR spectra of the crude product do not show resonances that could be assigned to the product of Oattack even though the reverse reaction of the corresponding benzhydryl enol ether to regenerate 1 c and 3 g should be much slower than those of the analogous adducts formed with the benzhydrylium ions 3 d or 3 f, which are 105-times
Scheme 2. Carbanions 1 a–e generated by deprotonation of 5-benzylated Meldrum’s acids (1-H) with potassium tert-butoxide.
Reactions of carbanions 1 with benzhydrylium ions 3 The combination of the potassium salt of 1 a with bis(Nmethyl-1,2,3,4-tetrahydroquinolin-6-yl)methylium tetrafluoroborate (3 d-BF4, for structure see Table 1) in DMSO resulted in the formation of 4 ad, indicating the electrophile’s attack at C5 of the Meldrum’s acid moiety of 1 a (Scheme 3). An analogous reaction occurred between 1 a-K and the bis(4-dimethylamino)-substituted benzhydrylium ion 3 f in acetonitrile and furnished 4 af in 52 % yield. Slow crystallization &
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Full Paper [1]0/[3]0 > 9 was maintained in all kinetic experiments. From the resulting monoexponential decay of the absorbance of the benzhydrylium ion 3 the first-order rate constant kobs was derived by a least-squares fitting of the function At = A0 exp(kobs t) + C (Figure 2 a). According to the relation kobs = kC[1], the first-order rate constants (kobs) depend linearly on the carbanion concentrations [1], as exemplified by Figure 2 b, whereby the slopes correspond to the second-order rate constants, kC, which are collected in Table 2.
Figure 1. X-ray crystal structure of 4 af (the asymmetric unit contains two formula units, one selected molecule is presented at the 50 % probability level, see the Supporting Information and ref. [31] for details). C2-C3-C4 113.93(15); C2-C3-C7 107.42(14); C2-C3-C16 113.36(13); C7-C3-C16 109.54(14); C4-C3-C16 104.91(13); C4-C3-C7 107.50(13); d(C3C7) = 156.5(2) pm; d(C3C16) = 158.2(2) pm.
Figure 2. a) Exponential decay of the absorbance at 622 nm during the reaction of 1 c-K (6.24 104 m) with 3 c-BF4 (2.17 105 m) in DMSO at 20 8C (stopped-flow technique). b) The correlation of the first-order rate constants, kobs, with the concentrations of 1 c is linear with a slope corresponding to the second-order rate constant, kC.
better electrofuges than 3 g.[32] As the adduct 4 cg with quaternized C-5 formed with high selectivity and was isolated in a yield of 79 %, we can exclude, furthermore, that side reactions play a major role.[33] Because the steric requirements at the negatively and positively charged reaction centers remain unchanged, we conclude that all combinations of the carbanions 1 a–e with the benzhydrylium ions 3 a–e that have been studied kinetically undergo analogous CC bond-forming reactions (see below).
Table 2. Second-order rate constants (kC) for the CC bond-forming reactions of the carbanions 1 with the benzhydrylium ions 3 (20 8C, DMSO).
Carbanions[a]
Ar2CH + [b]
kC [m1 s1]
1 a (R = NMe2)
(lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (ind)2CH + (3 c) (thq)2CH + (3 d) (pyr)2CH + (3 e) (ind)2CH + (3 c) (thq)2CH + (3 d) (pyr)2CH + (3 e)
6.63 103 1.84 104 7.33 104 2.37 105 7.65 103 1.49 104 5.44 104 1.71 105 5.69 103 1.45 104 4.13 104 1.39 105 6.37 103[c] 1.99 104[c] 1.57 105[c] 2.33 104 5.59 104 1.95 105 6.68 103 2.32 104 1.18 105
1 b (R = OMe)
Scheme 4. C-5 alkylation of carbanion 1 c by 3 g (yield of product after column chromatography).
1 c (R = H)
Kinetics of the reactions of the carbanions 1 with the benzhydrylium ions 3 1 c (R = H)[c]
As neither the carbanions 1 a–e nor the resulting covalent products 4 absorb light in the spectral region, where the benzhydrylium ions 3 a–e absorb strongly (450–700 nm), the kinetics of the reactions of the carbanions 1 a–e with the benzhydrylium ions 3 a–e in DMSO was followed by using stoppedflow UV/Vis spectroscopy. Additionally, the kinetics for the reactions of 1 c with the electrophiles 3 a–c were investigated in acetonitrile. In all experiments, first-order kinetics were achieved by applying an excess of the carbanions, that is, Chem. Eur. J. 2014, 20, 1 – 10
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1 d (R = CN)
1 e (R = NO2)
[a] Counterion: K + . [b] Counterion: BF4 . [c] In acetonitrile.
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Full Paper Figure 3 shows that the second-order rate constants (lg kC) from Table 2 correlate linearly with the electrophilicity parameters E of the benzhydrylium ions 3, as required by Equation (1). The slopes of these correlations equal the nucleophile-specific sensitivity parameter, sN, and the negative intercepts on the abscissa yield the corresponding nucleophilicity parameters, N, of the carbanions 1 a–e (Table 3). As the sN values of the carbanions 1 a–e vary noticeably (0.75 < sN < 1.2), their relative reactivities depend considerably on the electrophilic reaction partners. Reactivity comparisons solely based on the nucleophilicity parameters N of 1 a–e are, therefore, ambiguous.
products 2 and 6 are known (see the Supporting Information and ref. [37]), an unambiguous assignment of the signals was possible in all cases, as described in detail in the Supporting Information. As a consequence, we have not attempted to isolate the products of the studied hydride transfer reactions, which are tabulated in Table 5.
Table 4. Triarylcarbenium (tritylium) ions 5, their electrophilicity parameters (E) and pKR + values.
R1, R2, R3 NMe2, NMe2, H NMe2, OMe, H NMe2, H, H OMe, OMe, OMe OMe, OMe, H OMe, H, H Me, Me, Me H, H, H
5a 5b 5c 5d 5e 5f 5g 5h
E[a]
pKR + [b]
10.29 – 7.93 4.35 3.04 1.59[c] 1.21 0.51
6.94 4.86 3.88 0.82 1.24 3.40 3.56 6.63
[a] Electrophilicity, E, for reactions with primary amines and hydride donors as defined by Equation (1), from ref. [34]. [b] From ref. [35]. [c] From ref. [36].
Figure 3. Correlations of the second-order rate constants, lg kC, for the reactions of the carbanions 1 with the benzhydrylium ions Ar2CH + (3) in DMSO at 20 8C with the empirical electrophilicity parameters, E, of 3 (correlation for reactions of 1 b with 3 are not shown, see the Supporting Information, Figure S3).
Table 5. 1H NMR spectroscopic monitoring of the hydride transfer from carbanions 1 to tritylium ions 5 in deuterated acetonitrile (at 23(1) 8C). Table 3. Nucleophile-specific reactivity parameters N and sN of the carbanions 1 a–e and of the carbanion of Meldrum’s acid (C attack, in DMSO). Carbanion
N[a]
sN[a]
1 a (R = NMe2) 1 b (R = OMe) 1 c (R = H) 1 d (R = CN) 1 e (R = NO2)
14.48 15.13 15.02 13.79 12.02
0.86 0.75 0.75 0.86 1.17
13.91[b]
0.86[b]
[a] As defined by Equation (1). [b] From ref. [7].
The ratio kCMeCN/k CDMSO = 1.1 to 3.8 for the reactions of the parent carbanion 1 c with the benzhydrylium ions 3 a– c (Table 2) demonstrates that they proceed with similar rates in DMSO and acetonitrile.
Carbanion/tritylium combination
Reaction time
Products observed
1 a (R = NMe2) + 5 c 1 a (R = NMe2) + 5 f 1 a (R = NMe2) + 5 g 1 b (R = OMe) + 5 c 1 b (R = OMe) + 5 d 1 b (R = OMe) + 5 g 1 c (R = H) + 5 c 1 c (R = H) + 5 d
24 h 2h 5 min 5 min 5 min 5 min –[b] –[b]
2a+6c 2a+6 f 2a+6g 2 b + 6 c[a] 2b+6d 2b+6g 2c+6c 2c+6d
[a] After 5 min, about 15 % of the starting material was converted to products 2 b and 6 c. [b] The products were analyzed 96 h after mixing the reactants. The reaction time required for complete conversion of the reactants is shorter.
Reactions of the carbanions 1 with the tritylium ions 5 The reactions of the potassium salts (1 a–c)-K with the tritylium tetrafluoroborates 5-BF4 (Table 4) at ambient temperature in acetonitrile proceeded with the selective formation of the products of hydride transfer, 2 and 6, as observed by in situ 1 H NMR spectroscopy (Table 5). Since the 1H NMR spectra of &
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Kinetics of the reactions of the carbanions 1 with the tritylium ions 5 As described above for the kinetics of the reactions of the carbanions 1 with the benzhydrylium ions 3, conventional and 4
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Full Paper stopped-flow UV/Vis spectroscopic methods were used to follow the reactions of 1 with the tritylium ions 5 that are listed in Table 4. Typical kinetics for the reactions of the carbanions 1 with the tritylium ions 5 are shown in Figure 4. The decrease of the absorption at 525 nm, owing to the consumption of 5 b, was accompanied by an increase of the absorption at 450 nm, which indicates the formation of 2 a (Figure 4 a, b). The presence of an isosbestic point (Figure 4 b) demonstrates that the consumption of 5 b and the formation of 2 a are simultaneous processes that proceed at equal rates without the appearance of a significant concentration of an intermediate. The firstorder rate constant k = 7.80 105 s1 is derived from the decrease of the absorption at 525 nm (Figure 4 c) while k = 9.35 105 s1 is calculated from the increase of the absorption at 414 nm. As depicted for the reaction of 1 a with 5 b in Figure 4 d, the first-order rate constants, kobs, correlated linearly with the carbanion concentrations. As a consequence, the second-order rate constants, kH, for hydride transfer from the carbanions 1 a–c to the hydride acceptors 5 a–e were obtained from the slopes of such linear relationships (see Supporting Information for the individual correlations) and compiled in Table 6. For the reaction of 1 a with 5 b the kH values that are obtained by following either the decay of the absorption at 525 nm (kH = 0.130 m1 s1, Figure 4 d) or the increasing absorption at 414 nm (kH = 0.143 m1 s1, see the Supporting Information) agree within experimental error ( 10 %). The kinetics of the hydride transfer reactions of 5 with the carbanions 1 b and 1 c were generally determined by following the decay of the absorption of the tritylium ions 5. Details are specified in the footnotes of Table 6 and the Supporting Information. The rate constants (lg kH) increase linearly with the E parameters of the hydride-accepting tritylium ions 5 a,c–e (Figure 5). As tritylium ions (Ar3C + ) have previously been shown to be reliable reference electrophiles for characterizing the hydride donating abilities of BH, SiH, SnH, and CH hydride donors,[28] the correlations in Figure 5 enable us to characterize the hydride donor ability of the anions 1 a–c according to Equation (1). The resulting nucleophile-specific reactivity parameters N and sN are included in Figure 5. A different behavior was observed for combinations of carbanions 1 a and 1 c with tritylium ions of higher Lewis acidity, that is, for hydride transfer reactions from 1 a,c toward carbocations 5 f,g with an electrophilicity parameter E > 2 (or pKR + < 2). The UV/Vis spectroscopic monitoring of the reaction of the carbanion 1 a with the trimethyl-substituted tritylium (Figure 6 a) showed an instantaneous and quantitative disappearance of the absorbance at lmax = 450 nm owing to the rapid consumption of the tritylium ion 5 g immediately after mixing with 1 a (< 1 s), which was followed by a slow monoexponential increase of an absorption band at l = 450 nm that could be assigned to the unsaturated product 2 a. Fitting the function At = A0[1exp(kobs t)] + C to the curve in Figure 6 b gave a first-order rate constant of kobs = 5.49 102 s1 that did not depend on the concentration of the hydride donor 1 a, as demonstrated by the horizontal correlation line in Figure 6 c. Chem. Eur. J. 2014, 20, 1 – 10
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Figure 4. a) Hydride transfer from 1 a to 5 b in acetonitrile. b) Time-dependent UV/Vis spectra during the reaction of 5 b (lmax = 525 nm, c0 = 4.02 105 m) with 1 a (colorless, c0 = 4.84 104 m) in acetonitrile at 20 8C. c) Exponential decay of the absorbance, A, at 525 nm during the reaction of 1 a (4.84 104 m) with 5 b (4.54 105 m). d) Linear correlation of the first-order rate constants, kobs [s1], with the concentrations of 1 a with a slope corresponding to the second-order rate constant, kH [m1 s1].
The first-order rate constants for hydride transfer (kobs) from 1 a to 5 f,g as well as for the analogous reactions of 1 c with 5 f,g are collected in Table 6. The fast initial decay of the carbocation’s absorption and the independence of the rate constant for the formation of the unsaturated compound 2 a (or 2 c) of the concentration of the carbanion 1 a (or 1 c) is rationalized by the mechanism shown in Scheme 5. A fast but reversible oxygen attack of the highly Lewis acidic carbocations 5 at 1 leads to the quantitative formation of the colorless tritylated enol ethers 7. The backward reaction of 7 to 5 and 1 provides small concentrations of the hydride acceptor 5, which slowly oxidizes 1 (in excess) to form the hydride transfer products 2 and 6 that were observed by 5
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Full Paper Table 6. Second-order rate constants (kH) for the hydride transfer from the carbanions 1 a–c to the tritylium ions 5 a–g and first-order rate constants (kobs) for the formation of 2 (20 8C, MeCN). Carbanions[a] 1 a (R = NMe2)
1 b (R = OMe)
1 c (R = H)
Ar3C + [b] 5a 5b 5c 5d 5f 5g 5b 5c 5d 5e 5c 5d 5e 5f 5g
kH [m1 s1]
kobs [s1]
3 [c]
2.70 10 1.30 101 [c] 2.49 101 [d] 1.79 102 [d] 4.67 102 [c] 5.49 102 [c] 1.45 102 [d] 5.88 102 [d] 3.19 101 [d] 9.17 101[d] 1.74 102 [d] 1.12 101 [d] 3.64 101 [d] 7.59 103 [e] 7.67 103 [e]
[a] Counterion: K + . [b] Counterion: BF4 . [c] Derived from the increasing absorption of 2 a. [d] Derived from the decreasing absorption of the tritylium ion 5. [e] Derived from the increasing absorption of 2 c.
Figure 6. a) Time-dependent UV/Vis spectra of the reaction between 5 g–BF4 (c0 = 9.47 105 m) with 1 a-K (c0 = 3.38 103 m) in acetonitrile at 20 8C. b) Instantaneous fading followed by a slow increase of the absorbance, A, at 450 nm during the reaction of 5 g (c0 = 9.47 105 m) with 1 a (c0 = 3.38 103 m). c) Independence of the first-order rate constant of the concentration of carbanion 1 a.
Figure 5. Correlations of the second-order rate constants, lg kH, for the hydride transfer from the carbanions 1 a–c to the tritylium ions 5 in acetonitrile at 20 8C with the empirical electrophilicity parameters, E, of 5.
Scheme 5. Kinetically and thermodynamically controlled products of the reactions of carbanions 1 with the tritylium ions 5.
1
H NMR (Table 5) as well as by UV/Vis spectroscopy (Figure 6 a, b). According to Scheme 5, the decay of the concentration of 5 and the increase of the concentration of 2 follow the rate laws in Equations (2) and (3), respectively. Based on the UV/Vis spectroscopic monitoring of the reaction (Figure 6 a, b), we conclude that the attack of the highly Lewis acidic tritylium ions 5 at the oxygen of carbanions 1 to give the trityl enol ether 7 is much faster than the competing hydride transfer (kO @ kH). Owing to the negligible remaining concentrations of free carbocations 5, we can assume a quasi-stationary concentration of the tritylium ion 5 in the second phase of the reaction (d[5]/dt = 0), which allows us to rearrange Equations (2)–(4). Combination of Equation (3) with Equation (4) results in Equation (5). According to Equation (5), the rate of formation of the unsaturated product 2 is independent of the carbanion con&
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centration [1], in agreement with the results shown in Figure 6 c.
d½5=dt ¼ k O ½1½5k O ½7 þ k H ½1½5
ð2Þ
d½2=dt ¼ kH ½1½5
ð3Þ
For d[5]/dt = 0 in the second part of the reaction (conversion of 7 to 2 and 6):
½1½5 ¼ ðk O ½7Þ=ðk O þ kH Þ 6
ð4Þ
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Full Paper d½2=dt ¼ ½7 ðk H kO Þ=ðk O þ kH Þ
provided unequivocal evidence for the formation of this product of O-attack, because the alternative structure arising by C5attack should show resonances for two methyl and only one carbonyl carbon (in analogy to adducts 4). The ratio [7 b]/[2 b] changed from initially > 98:2 to 92:8 within 2.5 h at 20 8C (see the Supporting Information). After being warmed at ambient temperature, the 1H resonances of 7 b had vanished completely and the resonances of the hydride transfer products 2 b and 6 h could be detected. Thus, the observations made by NMR spectroscopy mirror those made by photometry (Figure 6) and corroborate the mechanistic proposal in Scheme 5.
ð5Þ
For kO @ kH :
d½2=dt ¼ ½7ðk H kO Þ=k O ¼ ðk H =K O Þ½7
ð6Þ
Since kO @ kH, Equation (5) simplifies to Equation (6) and, because of the relation KO = kO/kO, finally yields kobs = kH/KO. Using the N and sN parameters of 1 a and 1 c from Figure 5 and the electrophilicities E of the tritylium ions 5 f and 5 g from Table 4 Equation (1) allows the calculation of the second-order rate constants kH for the hydride transfer reactions listed in Table 7 that gave kinetics for the formation of the arylidene Meldrum’s acids 2, which are independent of the concentration of the enolates 1. Equilibrium constants for the O-attack, KO, can then be derived for these enolate-carbocation combinations from the ratio kH/kobs (Table 7).
Table 7. Calculation of equilibrium constants for the O-attack (KO) from the experimental (kobs) and extrapolated (kH) hyride transfer rate constants. Carbanion
Ar3C +
kH[a] [m1 s1]
kobs[b] [s1]
KO [m1]
1 a (R = NMe2)
5f 5g 5f 5g
3.19 104 6.48 104 5.55 102 1.02 103
4.67 102 5.49 102 7.59 103 7.67 103
6.8 105 1.2 106 7.3 104 1.3 105
1 c (R = H)
[a] Calculated by substituting N (and sN) from Figure 5 and E from Table 4 into Equation (1). [b] From Table 6.
Scheme 6. Reversible formation of the O-adduct 7 b from 1 b and 5 h at 20 8C and its conversion to the final products 2 b and 6 h after being warmed to ambient temperature.
Since the substituent R is not in direct conjugation with the carbanionic center of 1, carbanion 1 a is only slightly more Lewis basic than 1 c. In agreement with their similar pKR + values (Table 4), the tritylium ions 5 f and 5 g possess similar Lewis acidities towards 1 a and 1 c. Though the reactions of 1 a,c with 5 f,g were thus postulated to quantitatively generate the corresponding adducts 7 at ambient temperature, the NMR spectroscopic characterization of species 7 was unsuccessful because of the fast subsequent conversion of 7 to the products of hydride transfer 2 and 6. As decreasing stabilization of the tritylium ion 5 can be expected to affect the equilibrium constants KO more than the rate constants kH, Equation (6) predicts a prolonged life time of adducts 7 when less stabilized tritylium ions are employed. Indeed, mixing of the parent tritylium tetrafluoroborate 5 h-BF4 with 1 b-K in CD3CN at ambient temperature resulted in the detection of a new species by 1H NMR spectroscopy that disappeared within minutes to produce the known resonances of the hydride transfer products 2 b and 6 h (Scheme 6). By lowering the reaction temperature to 20 8C, we finally succeeded in trapping the O-adduct 7 b formed by addition of the parent tritylium ion 5 h to the methoxy-substituted carbanion 1 b (Scheme 6). The life time of 7 b in CD3CN solution at 20 8C was sufficiently long to record 1H and 13C NMR spectra that Chem. Eur. J. 2014, 20, 1 – 10
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The appearance of an additional singlet at dH = 2.09 ppm, assigned to the formation of acetone (ca. 35 %), indicated that the pathway shown in Scheme 6 is accompanied by a subordinate second process. In accord with literature reports,[33] a retro-hetero-Diels–Alder reaction of 7 b might account for the formation of the traces of acetone. This side reaction is not shown in Scheme 6 as it does not affect the kinetics [Eqs. (2)– (6)] of the formation of the unsaturated arylidene Meldrum’s acids 2. Variation of X will have the same, but opposite effect on DG0 of the hydride abstraction from the carbanions 1 by any carbocation R + as on DG0 of the hydride addition to the benzylidene Meldrum’s acids 2. Yet, Scheme 7 shows that replacement of X = H by OMe retards the hydride addition about twotimes more than it accelerates the hydride abstraction, whereas replacement of X = OMe by NMe2 has a seven-times larger effect on the hydride addition than on the hydride abstraction. This trend corresponds to our previous observation that in hydride transfer reactions to carbocations, substituent effects in the hydride acceptors have a much greater impact on the 7
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Full Paper only be generated in such small equilibrium concentrations that they were not detectable. For this reason, it is possible to measure the second-order rate constants for the hydride abstractions from 1 by these carbocations. Since hydride abstractions by tritylium ions can be described by Equation (1), it is possible to calculate N and sN for the hydride donor abilities of 1 a–c and compare them with those of other hydride donors (Scheme 9). As the parameters N for the hydride donicities of 1 a–c are 8–10 units smaller than for their C-reactivities, benzhydrylium ions react exclusively with CC bond formation.
Scheme 7. Rate constants (at 20 8C) for hydride abstractions from 1 a–c by carbocations R + (kH, in MeCN, from Table 6) and hydride additions to benzylidene Meldrum’s acids 2 a–c (kadd, in dichloromethane, from ref. [38]).
rate constants of hydride transfer than the same substituent variation in the hydride donor (Scheme 8).[39] Our explanation that electron donors generally reduce the rate of the identity reactions and, therefore, reduce the hydride-accepting ability of the carbocation more than they increase the hydride-donating ability of the alkene[40] can analogously Scheme 8. Hydride transfer between carbocations and be employed to rationalize the unsaturated hydride donors. trends in Scheme 7. Scheme 9. Comparison of the hydride donating abilities of carbanions 1 a– c with those of various other CH, SiH, SnH, and BH hydride donors (in dichloromethane or acetonitrile if not mentioned otherwise, from ref. [28]).
Conclusion With nucleophilicity parameters 12 < N < 15, the 5-benzylsubstituted anions of Meldrum’s acid have similar nucleophilic C-reactivities as the anion derived from the parent Meldrum’s acid (Table 3), in line with previous observations that methyl groups at the carbanionic center of diethyl malonate or acetylacetonide anions have little effect on their nucleophilic reactivities.[9, 14] Obviously, C-nucleophilicity is much greater than the hydride-donating ability, as in none of the reactions of the carbanions 1 with the benzhydrylium ions 3 the formation of the hydride abstraction products 2 was observed. We have repeatedly mentioned that steric effects are not explicitly considered by Equation (1), which, therefore, cannot be used for reactions of bulky reagents (e.g., tritylium ions)[34, 35] though we have recently reported that Equation (1) is applicable to reactions of trityl cations with primary amines and hydride donors.[28, 34, 41, 42] Indeed, tritylium ions do not react with the anions 1 to form CC bonds. Highly reactive tritylium ions react with the oxygen of the anions 1 to give trityl enol ethers, which subsequently decompose with formation of the hydride transfer products 2 and 6 and, to a minor extent, by retrohetero-Diels–Alder pathways.[33] In contrast, the Lewis acidities of the dimethoxy and better donor-substituted tritylium ions 5 a–e are so low that the intermediate trityl enol ethers 7 can &
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Experimental Section Study of C reactivity The kinetics of the reactions of the carbanions 1 with the benzhydrylium ions Ar2CH + (3) were followed photometrically at or close to the absorption maxima of Ar2CH + by using stopped-flow UV/Vis spectroscopy. The pseudo-first-order rate constants kobs [s1] were obtained by least-squares fitting of the decaying absorbance of Ar2CH + to the monoexponential function At = A0 exp(kobs t) + C. The second-order rate constants kC [m1 s1] were then obtained from the slopes of the linear correlations of kobs with the concentrations of the carbanions.
Study of hydride transfer rates The reactions of the carbanions 1 with the triarylmethylium ions Ar3C + (5) were followed photometrically at or close to the absorption maxima of either 5 or the benzylidene Meldrum’s acids 2 by using conventional or stopped-flow UV/Vis spectroscopy. The pseudo-first-order rate constants kobs [s1] were obtained by leastsquares fitting of the decaying absorbance of 5 to the monoexponential function At = A0 exp(kobs t) + C or of the increasing absorbance of the unsaturated products 2 to the monoexponential func-
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Full Paper tion At = A0·[1exp(kobs t)] + C. The second-order rate constants kH [m1 s1] were then obtained from the slopes of the linear correlations of kobs with the concentrations of the carbanions. The kobs of the formation of 2 a and 2 c through the reactions of tritylium ions 5 f,g with carbanions 1 a and 1 c, respectively, were found to be independent of the concentrations of the carbanions. For further details, see the Supporting Information.
[25] [26]
Acknowledgements Financial support by the Deutsche Forschungsgemeinschaft (SFB 749, project B1) is gratefully acknowledged. We thank Dr. Peter Mayer (LMU Mnchen) for determining the X-ray crystal structure of 4 af.
[27]
[28]
Keywords: alkylation · ambident reactivity · carbocations · kinetics · linear free energy relationships
[29]
[1] F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, 5th ed., Part B: Reactions and Synthesis, Springer, New York, 2008, Chapter 1. [2] H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990 – 1010; Angew. Chem. Int. Ed. Engl. 1994, 33, 938 – 957. [3] H. Mayr, B. Kempf, A. R. Ofial, Acc. Chem. Res. 2003, 36, 66 – 77. [4] A. R. Ofial, H. Mayr, Macromol. Symp. 2004, 215, 353 – 367. [5] H. Mayr, A. R. Ofial, Pure Appl. Chem. 2005, 77, 1807 – 1821. [6] H. Mayr, A. R. Ofial, J. Phys. Org. Chem. 2008, 21, 584 – 595. [7] R. Lucius, R. Loos, H. Mayr, Angew. Chem. 2002, 114, 97 – 102; Angew. Chem. Int. Ed. 2002, 41, 91 – 95. [8] T. Lemek, H. Mayr, J. Org. Chem. 2003, 68, 6880 – 6886. [9] T. Bug, H. Mayr, J. Am. Chem. Soc. 2003, 125, 12980 – 12986. [10] T. Bug, T. Lemek, H. Mayr, J. Org. Chem. 2004, 69, 7565 – 7576. [11] S. T. A. Berger, A. R. Ofial, H. Mayr, J. Am. Chem. Soc. 2007, 129, 9753 – 9761. [12] S. T. A. Berger, T. Lemek, H. Mayr, ARKIVOC 2008 (x), 37 – 53. [13] F. Seeliger, H. Mayr, Org. Biomol. Chem. 2008, 6, 3052 – 3058. [14] O. Kaumanns, R. Appel, T. Lemek, F. Seeliger, H. Mayr, J. Org. Chem. 2009, 74, 75 – 81. [15] R. Appel, R. Loos, H. Mayr, J. Am. Chem. Soc. 2009, 131, 704 – 714. [16] R. Appel, H. Mayr, Chem. Eur. J. 2010, 16, 8610 – 8614. [17] F. Corral-Bautista, H. Mayr, Eur. J. Org. Chem. 2013, 4255 – 4261. [18] T. B. Phan, H. Mayr, Eur. J. Org. Chem. 2006, 2530 – 2537. [19] a) T. H. Black, Org. Prep. Proceed. Int. 1989, 21, 179 – 217; b) J. Clayden, N. Greeves, S. Warren, Organic Chemistry, 2nd ed., Oxford University Press, Oxford, 2012. [20] O. A. Reutov, I. P. Beletskaya, A. L. Kurts, Ambident Anions, Consultants Bureau, New York, 1983. [21] R. G. Pearson, Chemical Hardness, Wiley-VCH, Weinheim, 1997. [22] a) S. Hnig, Angew. Chem. 1964, 76, 400 – 412; Angew. Chem. Int. Ed. Engl. 1964, 3, 548 – 560; b) R. Gompper, Angew. Chem. 1964, 76, 412 – 423; Angew. Chem. Int. Ed. Engl. 1964, 3, 560 – 570; c) R. S. Drago, J. Chem. Educ. 1974, 51, 300 – 307; d) R. Gompper, H.-U. Wagner, Angew. Chem. 1976, 88, 389 – 401; Angew. Chem. Int. Ed. Engl. 1976, 15, 321 – 333; e) J. A. Berson, Angew. Chem. 2006, 118, 4842 – 4847; Angew. Chem. Int. Ed. 2006, 45, 4724 – 4729. [23] H. Mayr, M. Breugst, A. R. Ofial, Angew. Chem. 2011, 123, 6598 – 6634; Angew. Chem. Int. Ed. 2011, 50, 6470 – 6505. [24] a) M. T. Reetz, W. Stephan, Angew. Chem. 1977, 89, 46; Angew. Chem. Int. Ed. Engl. 1977, 16, 44; b) M. T. Reetz, F. Eibach, Angew. Chem. 1978, 90, 285 – 286; Angew. Chem. Int. Ed. Engl. 1978, 17, 278 – 279; c) M. T. Reetz,
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F. Eibach, Liebigs Ann. Chem. 1978, 1598 – 1606; d) O. L. Farng, T. C. Bruice, J. Chem. Soc. Chem. Commun. 1984, 185 – 186; e) C. F. Bernasconi, M. W. Stronach, C. H. DePuy, S. Gronert, J. Am. Chem. Soc. 1990, 112, 9044 – 9052; f) B.-A. Feit, S. Shapira, A. Herbst, Tetrahedron 1995, 51, 317 – 328. a) A. M. Dumas, E. Fillion, Acc. Chem. Res. 2010, 43, 440 – 454; b) I. Mierina, Synlett 2014, 25, 155 – 156. For fundamental studies on the acidity of Meldrum’s acid and the stabilization of the corresponding anions: a) E. M. Arnett, S. G. Maroldo, S. L. Schilling, J. A. Harrelson, J. Am. Chem. Soc. 1984, 106, 6759 – 6767; b) E. M. Arnett, J. A. Harrelson, Jr., J. Am. Chem. Soc. 1987, 109, 809 – 812; c) J. D. Evanseck, K. N. Houk, J. M. Briggs, W. L. Jorgensen, J. Am. Chem. Soc. 1994, 116, 10630 – 10638; d) K. Byun, Y. Mo, J. Gao, J. Am. Chem. Soc. 2001, 123, 3974 – 3979; e) S. Nakamura, H. Hirao, T. Ohwada, J. Org. Chem. 2004, 69, 4309 – 4316; f) M. Karni, C. F. Bernasconi, Z. Rappoport, J. Org. Chem. 2008, 73, 2980 – 2994. H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker, B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J. Am. Chem. Soc. 2001, 123, 9500 – 9512. M. Horn, L. H. Schappele, G. Lang-Wittkowski, H. Mayr, A. R. Ofial, Chem. Eur. J. 2013, 19, 249 – 263. a) O. Kaumanns, H. Mayr, J. Org. Chem. 2008, 73, 2738 – 2745; for a study on the solvent dependence of Knoevenagel condensations: b) H. S. Sandhu, S. Sapra, M. Gupta, K. Nepali, R. Gautam, S. Yadav, R. Kumar, S. M. Jachak, M. Chugh, M. K. Gupta, O. P. Suri, K. L. Dhar, Bioorg. Med. Chem. 2010, 18, 5626 – 5633. a) A. D. Wright, M. L. Haslego, F. X. Smith, Tetrahedron Lett. 1979, 20, 2325 – 2326; b) U. V. Desai, D. M. Pore, R. B. Mane, S. B. Solabannavar, P. P. Wadgaonkar, Synth. Commun. 2004, 34, 25 – 32. CCDC-987379 (4 af) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_ request/cif. N. Streidl, B. Denegri, O. Kronja, H. Mayr, Acc. Chem. Res. 2010, 43, 1537 – 1549. Decompositions of O-methylated Meldrum’s acids by retro-heteroDiels–Alder reactions have previously been reported: a) J. Swoboda, J. Derkosch, F. Wessely, Monatsh. Chem. 1960, 91, 188 – 201; b) S. I. Zav’yalov, Izv. Akad. Nauk SSSR Ser. Khim. 1961, 2185 – 2189; c) G. A. Bihlmayer, P. Schuster, O. E. Polansky, Monatsh. Chem. 1966, 97, 145 – 149; d) K. Matoba, T. Yamazaki, Chem. Pharm. Bull. 1983, 31, 2955 – 2956; e) M. Sato, H. Ban, C. Kaneko, Tetrahedron Lett. 1997, 38, 6689 – 6692; f) E. Fillion, D. Fishlock, Tetrahedron 2009, 65, 6682 – 6695. S. Minegishi, H. Mayr, J. Am. Chem. Soc. 2003, 125, 286 – 295. M. Horn, H. Mayr, J. Phys. Org. Chem. 2012, 25, 979 – 988. M. Horn, C. Metz, H. Mayr, Eur. J. Org. Chem. 2011, 6476 – 6485. a) J. Le Bras, J. Muzart, Tetrahedron 2007, 63, 7942 – 7948; b) P. Thirupathi, S. S. Kim, Tetrahedron 2010, 66, 2995 – 3003; c) H. Meier, S. Kim, Eur. J. Org. Chem. 2001, 1163 – 1167. D. Richter, H. Mayr, Angew. Chem. 2009, 121, 1992 – 1995; Angew. Chem. Int. Ed. 2009, 48, 1958 – 1961. H. Mayr, G. Lang, A. R. Ofial, J. Am. Chem. Soc. 2002, 124, 4076 – 4083. a) E.-U. Wrthwein, G. Lang, L. H. Schappele, H. Mayr, J. Am. Chem. Soc. 2002, 124, 4084 – 4092; b) see also: I.-S. H. Lee, K.-H. Chow, M. M. Kreevoy, J. Am. Chem. Soc. 2002, 124, 7755 – 7761; c) I.-S. H. Lee, Y. R. Ji, E. H. Jeoung, J. Phys. Chem. A 2006, 110, 3875 – 3881. M. Horn, H. Mayr, Eur. J. Org. Chem. 2011, 6470 – 6475. Kinetic studies with surface coordinated tritylium ions: S. Spange, S. Adolph, R. Walther, Y. Zimmermann, J. Phys. Chem. B 2003, 107, 298 – 305.
Received: April 18, 2014 Published online on && &&, 0000
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FULL PAPER & Ambident Reactivity
Several options: Carbocations react with the anions of 5-benzylated Meldrum’s acids by attack at the enolate carbon or oxygen or through hydride abstraction (see illustration). Kinetic studies with benzhydrylium and tritylium ions reveal the preferred pathways.
X. Chen, Y. Tan, G. Berionni, A. R. Ofial,* H. Mayr && – && Di- and Triarylmethylium Ions as Probes for the Ambident Reactivities of Carbanions Derived from 5Benzylated Meldrum’s Acid
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& Ambident Reactivity
Di- and Triarylmethylium Ions as Probes for the Ambident Reactivities of Carbanions Derived from 5-Benzylated Meldrum’s Acid Xi Chen, Yue Tan, Guillaume Berionni, Armin R. Ofial,* and Herbert Mayr[a] Dedicated to Professor Hans-Ulrich Reißig on the occasion of his 65th birthday
Abstract: The kinetics of the reactions of carbocations with carbanions 1 derived from 5-benzyl-substituted Meldrum’s acids 1-H (Meldrum’s acid = 2,2-dimethyl-1,3-dioxane-4,6dione) were investigated by UV/Vis spectroscopic methods. Benzhydryl cations Ar2CH + added exclusively to C-5 of the Meldrum’s acid moiety. As the second-order rate constants (kC) of these reactions in DMSO followed the linear freeenergy relationship lg k = sN(N+E), the nucleophile-specific
reactivity parameters N and sN for the carbanions 1 could be determined. In contrast, trityl cations Ar3C + reacted differently. While tritylium ions of low electrophilicity (E < 2) reacted with 1 through rate-determining b-hydride abstraction, more Lewis acidic tritylium ions initially reacted at the carbonyl oxygen of 1 to form trityl enolates, which subsequently reionized and eventually yielded triarylmethanes and 5-benzylidene Meldrum’s acids by hydride transfer.
Introduction
of the alkylation reactions were mostly interpreted on the basis of the principle of hard and soft acids and bases (HSAB principle),[21] which predicts O-alkylation with hard and C-alkylation with soft electrophiles. Because the HSAB principle neither differentiates between kinetic and thermodynamic control nor considers the diffusion limit, it often fails to predict the correct regioselectivity.[22] An alternative treatment of ambident reactivity based on Marcus theory has, therefore, been proposed and applied to reactions of enolate ions.[23] A third reaction channel exists for enolate ions that carry hydrogen atoms in b-position to the carbonyl group. As described for several examples, such enolates may react with carbocations or Michael acceptors by b-hydride transfer to give olefins.[24] We now report that carbanions derived from 5-benzylated Meldrum’s acid (1)[25, 26] react with carbocations through all three mentioned paths (Scheme 1), which makes kinetic studies of their reactivity rather challenging. By using benzhydrylium ions and tritylium ions as electrophilic probes it has been possible to investigate independently the rates of CC bond formation and hydride transfer of Meldrum’s acid derived carbanions 1 and to assign reactivity parameters N and sN to the different positions. A set of benzhydrylium ions, Ar2CH + , served as reference electrophiles[27] for the determination of the carbon reactivity of 1. Tritylium ions (Ar3C + ) are sterically more demanding and cannot react with C-5 of the Meldrum’s acid moiety of 1. Yet, they have recently been shown to act as reliable reference electrophiles for the determination of hydride donating abilities of several types of hydride donors,[28] which made them promising candidates to study the hydride transfer rates of carbanions 1. Both types of carbocations may alternatively attack
Carbonyl-substituted carbanions (enolates) or related organometallic species are usually generated with the aim to make use of their reactivity at carbon, for example, for CC bond forming reactions.[1] In order to quantify the nucleophilic carbon reactivity of enolate anions, we have previously investigated the kinetics of their reactions with benzhydrylium ions (Ar2CH + ) and structurally related quinone methides. Analysis of the second-order rate constants (k) of these reactions by the correlation Equation (1),[2–6] in which E describes the reactivity of the reference electrophiles, provided the nucleophile-specific, solvent-dependent nucleophilicity parameters N (and sensitivities sN) for enolates and other types of acceptor-stabilized carbanions in DMSO,[7–17] water,[9, 10] and methanolic solutions.[11, 18] lg k 20 o C ¼ sN ðN þ EÞ
ð1Þ
As ambident nucleophiles, enolates can alternatively undergo O-alkylation with formation of enol ethers, a reaction course that is frequently used for the protection of carbonyl groups.[19] The site of attack depends on the structure of the enolate as well as on the nature of the electrophile, the solvent, and the counterion.[20] In the past, the regioselectivities [a] Dr. X. Chen,+ Dr. Y. Tan,+ Dr. G. Berionni, Dr. A. R. Ofial, Prof. Dr. H. Mayr Department Chemie, Ludwig-Maximilians-Universitt Mnchen Butenandtstr. 5–13, 81377 Mnchen (Germany) E-mail: [email protected] [+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403161. Chem. Eur. J. 2014, 20, 1 – 10
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Full Paper Table 1. Benzhydrylium ions (Ar2CH + ) 3 used as reference electrophiles in this work and their electrophilicity parameters, E. E[a]
Ar2CH +
(lil)2CH + (3 a)
10.04
(jul)2CH + (3 b)
9.45
(ind)2CH + (3 c)
8.76
(thq)2CH + (3 d)
8.22
(pyr)2CH + (3 e)
7.69
(dma)2CH + (3 f)
7.02
+
Scheme 1. Possible reactivities of carbanions 1 towards carbocations R .
at oxygen to give enol ethers, which was only observable when tritylium ions of high Lewis acidity were employed.
Results and Discussion Synthesis of potassium salts 1K
(ani)2CH + (3 g)
Knoevenagel condensations of substituted benzaldehydes with Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione)[29] and reduction of the resulting benzylidene Meldrum’s acids 2 a– e with sodium borohydride followed by acidic work-up generated the carbanion precursors 1-H (Scheme 2).[30] Subsequent treatment of the 5-arylmethyl-2,2-dimethyl-1,3-dioxane-4,6diones (1 a–e)-H with equimolar amounts of potassium tertbutoxide in ethanol gave rise to the precipitation of the potassium salts (1 a–e)-K, which were collected by filtration and characterized by NMR spectroscopy.
0.00
[a] From ref. [27].
Scheme 3. Products from CC bond-forming reactions of carbanion 1 a with the benzhydrylium tetrafluoroborates 3 d-BF4 (in DMSO) and 3 f-BF4 (in MeCN); yields of products after crystallization.
from ethyl acetate gave crystals of 4 af that were suitable for single crystal X-ray analysis (Figure 1) and provided unequivocal evidence for the CC bond formation between carbocation 3 f and carbanion 1 a.[31] The long C3C16 bond (158.2(2) pm) can be explained by steric strain and incipient heterolysis of this CC bond though the NMR spectroscopy data do not provide clear evidence for this effect. Attack at C-5 was also observed in the reaction of the ambident nucleophile 1 c-K with the bis(p-anisyl)methylium ion 3 g, which is by a factor of > 107 more electrophilic than 3 d or 3 f (Scheme 4). The NMR spectra of the crude product do not show resonances that could be assigned to the product of Oattack even though the reverse reaction of the corresponding benzhydryl enol ether to regenerate 1 c and 3 g should be much slower than those of the analogous adducts formed with the benzhydrylium ions 3 d or 3 f, which are 105-times
Scheme 2. Carbanions 1 a–e generated by deprotonation of 5-benzylated Meldrum’s acids (1-H) with potassium tert-butoxide.
Reactions of carbanions 1 with benzhydrylium ions 3 The combination of the potassium salt of 1 a with bis(Nmethyl-1,2,3,4-tetrahydroquinolin-6-yl)methylium tetrafluoroborate (3 d-BF4, for structure see Table 1) in DMSO resulted in the formation of 4 ad, indicating the electrophile’s attack at C5 of the Meldrum’s acid moiety of 1 a (Scheme 3). An analogous reaction occurred between 1 a-K and the bis(4-dimethylamino)-substituted benzhydrylium ion 3 f in acetonitrile and furnished 4 af in 52 % yield. Slow crystallization &
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Full Paper [1]0/[3]0 > 9 was maintained in all kinetic experiments. From the resulting monoexponential decay of the absorbance of the benzhydrylium ion 3 the first-order rate constant kobs was derived by a least-squares fitting of the function At = A0 exp(kobs t) + C (Figure 2 a). According to the relation kobs = kC[1], the first-order rate constants (kobs) depend linearly on the carbanion concentrations [1], as exemplified by Figure 2 b, whereby the slopes correspond to the second-order rate constants, kC, which are collected in Table 2.
Figure 1. X-ray crystal structure of 4 af (the asymmetric unit contains two formula units, one selected molecule is presented at the 50 % probability level, see the Supporting Information and ref. [31] for details). C2-C3-C4 113.93(15); C2-C3-C7 107.42(14); C2-C3-C16 113.36(13); C7-C3-C16 109.54(14); C4-C3-C16 104.91(13); C4-C3-C7 107.50(13); d(C3C7) = 156.5(2) pm; d(C3C16) = 158.2(2) pm.
Figure 2. a) Exponential decay of the absorbance at 622 nm during the reaction of 1 c-K (6.24 104 m) with 3 c-BF4 (2.17 105 m) in DMSO at 20 8C (stopped-flow technique). b) The correlation of the first-order rate constants, kobs, with the concentrations of 1 c is linear with a slope corresponding to the second-order rate constant, kC.
better electrofuges than 3 g.[32] As the adduct 4 cg with quaternized C-5 formed with high selectivity and was isolated in a yield of 79 %, we can exclude, furthermore, that side reactions play a major role.[33] Because the steric requirements at the negatively and positively charged reaction centers remain unchanged, we conclude that all combinations of the carbanions 1 a–e with the benzhydrylium ions 3 a–e that have been studied kinetically undergo analogous CC bond-forming reactions (see below).
Table 2. Second-order rate constants (kC) for the CC bond-forming reactions of the carbanions 1 with the benzhydrylium ions 3 (20 8C, DMSO).
Carbanions[a]
Ar2CH + [b]
kC [m1 s1]
1 a (R = NMe2)
(lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (thq)2CH + (3 d) (lil)2CH + (3 a) (jul)2CH + (3 b) (ind)2CH + (3 c) (ind)2CH + (3 c) (thq)2CH + (3 d) (pyr)2CH + (3 e) (ind)2CH + (3 c) (thq)2CH + (3 d) (pyr)2CH + (3 e)
6.63 103 1.84 104 7.33 104 2.37 105 7.65 103 1.49 104 5.44 104 1.71 105 5.69 103 1.45 104 4.13 104 1.39 105 6.37 103[c] 1.99 104[c] 1.57 105[c] 2.33 104 5.59 104 1.95 105 6.68 103 2.32 104 1.18 105
1 b (R = OMe)
Scheme 4. C-5 alkylation of carbanion 1 c by 3 g (yield of product after column chromatography).
1 c (R = H)
Kinetics of the reactions of the carbanions 1 with the benzhydrylium ions 3 1 c (R = H)[c]
As neither the carbanions 1 a–e nor the resulting covalent products 4 absorb light in the spectral region, where the benzhydrylium ions 3 a–e absorb strongly (450–700 nm), the kinetics of the reactions of the carbanions 1 a–e with the benzhydrylium ions 3 a–e in DMSO was followed by using stoppedflow UV/Vis spectroscopy. Additionally, the kinetics for the reactions of 1 c with the electrophiles 3 a–c were investigated in acetonitrile. In all experiments, first-order kinetics were achieved by applying an excess of the carbanions, that is, Chem. Eur. J. 2014, 20, 1 – 10
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1 d (R = CN)
1 e (R = NO2)
[a] Counterion: K + . [b] Counterion: BF4 . [c] In acetonitrile.
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Full Paper Figure 3 shows that the second-order rate constants (lg kC) from Table 2 correlate linearly with the electrophilicity parameters E of the benzhydrylium ions 3, as required by Equation (1). The slopes of these correlations equal the nucleophile-specific sensitivity parameter, sN, and the negative intercepts on the abscissa yield the corresponding nucleophilicity parameters, N, of the carbanions 1 a–e (Table 3). As the sN values of the carbanions 1 a–e vary noticeably (0.75 < sN < 1.2), their relative reactivities depend considerably on the electrophilic reaction partners. Reactivity comparisons solely based on the nucleophilicity parameters N of 1 a–e are, therefore, ambiguous.
products 2 and 6 are known (see the Supporting Information and ref. [37]), an unambiguous assignment of the signals was possible in all cases, as described in detail in the Supporting Information. As a consequence, we have not attempted to isolate the products of the studied hydride transfer reactions, which are tabulated in Table 5.
Table 4. Triarylcarbenium (tritylium) ions 5, their electrophilicity parameters (E) and pKR + values.
R1, R2, R3 NMe2, NMe2, H NMe2, OMe, H NMe2, H, H OMe, OMe, OMe OMe, OMe, H OMe, H, H Me, Me, Me H, H, H
5a 5b 5c 5d 5e 5f 5g 5h
E[a]
pKR + [b]
10.29 – 7.93 4.35 3.04 1.59[c] 1.21 0.51
6.94 4.86 3.88 0.82 1.24 3.40 3.56 6.63
[a] Electrophilicity, E, for reactions with primary amines and hydride donors as defined by Equation (1), from ref. [34]. [b] From ref. [35]. [c] From ref. [36].
Figure 3. Correlations of the second-order rate constants, lg kC, for the reactions of the carbanions 1 with the benzhydrylium ions Ar2CH + (3) in DMSO at 20 8C with the empirical electrophilicity parameters, E, of 3 (correlation for reactions of 1 b with 3 are not shown, see the Supporting Information, Figure S3).
Table 5. 1H NMR spectroscopic monitoring of the hydride transfer from carbanions 1 to tritylium ions 5 in deuterated acetonitrile (at 23(1) 8C). Table 3. Nucleophile-specific reactivity parameters N and sN of the carbanions 1 a–e and of the carbanion of Meldrum’s acid (C attack, in DMSO). Carbanion
N[a]
sN[a]
1 a (R = NMe2) 1 b (R = OMe) 1 c (R = H) 1 d (R = CN) 1 e (R = NO2)
14.48 15.13 15.02 13.79 12.02
0.86 0.75 0.75 0.86 1.17
13.91[b]
0.86[b]
[a] As defined by Equation (1). [b] From ref. [7].
The ratio kCMeCN/k CDMSO = 1.1 to 3.8 for the reactions of the parent carbanion 1 c with the benzhydrylium ions 3 a– c (Table 2) demonstrates that they proceed with similar rates in DMSO and acetonitrile.
Carbanion/tritylium combination
Reaction time
Products observed
1 a (R = NMe2) + 5 c 1 a (R = NMe2) + 5 f 1 a (R = NMe2) + 5 g 1 b (R = OMe) + 5 c 1 b (R = OMe) + 5 d 1 b (R = OMe) + 5 g 1 c (R = H) + 5 c 1 c (R = H) + 5 d
24 h 2h 5 min 5 min 5 min 5 min –[b] –[b]
2a+6c 2a+6 f 2a+6g 2 b + 6 c[a] 2b+6d 2b+6g 2c+6c 2c+6d
[a] After 5 min, about 15 % of the starting material was converted to products 2 b and 6 c. [b] The products were analyzed 96 h after mixing the reactants. The reaction time required for complete conversion of the reactants is shorter.
Reactions of the carbanions 1 with the tritylium ions 5 The reactions of the potassium salts (1 a–c)-K with the tritylium tetrafluoroborates 5-BF4 (Table 4) at ambient temperature in acetonitrile proceeded with the selective formation of the products of hydride transfer, 2 and 6, as observed by in situ 1 H NMR spectroscopy (Table 5). Since the 1H NMR spectra of &
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Kinetics of the reactions of the carbanions 1 with the tritylium ions 5 As described above for the kinetics of the reactions of the carbanions 1 with the benzhydrylium ions 3, conventional and 4
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Full Paper stopped-flow UV/Vis spectroscopic methods were used to follow the reactions of 1 with the tritylium ions 5 that are listed in Table 4. Typical kinetics for the reactions of the carbanions 1 with the tritylium ions 5 are shown in Figure 4. The decrease of the absorption at 525 nm, owing to the consumption of 5 b, was accompanied by an increase of the absorption at 450 nm, which indicates the formation of 2 a (Figure 4 a, b). The presence of an isosbestic point (Figure 4 b) demonstrates that the consumption of 5 b and the formation of 2 a are simultaneous processes that proceed at equal rates without the appearance of a significant concentration of an intermediate. The firstorder rate constant k = 7.80 105 s1 is derived from the decrease of the absorption at 525 nm (Figure 4 c) while k = 9.35 105 s1 is calculated from the increase of the absorption at 414 nm. As depicted for the reaction of 1 a with 5 b in Figure 4 d, the first-order rate constants, kobs, correlated linearly with the carbanion concentrations. As a consequence, the second-order rate constants, kH, for hydride transfer from the carbanions 1 a–c to the hydride acceptors 5 a–e were obtained from the slopes of such linear relationships (see Supporting Information for the individual correlations) and compiled in Table 6. For the reaction of 1 a with 5 b the kH values that are obtained by following either the decay of the absorption at 525 nm (kH = 0.130 m1 s1, Figure 4 d) or the increasing absorption at 414 nm (kH = 0.143 m1 s1, see the Supporting Information) agree within experimental error ( 10 %). The kinetics of the hydride transfer reactions of 5 with the carbanions 1 b and 1 c were generally determined by following the decay of the absorption of the tritylium ions 5. Details are specified in the footnotes of Table 6 and the Supporting Information. The rate constants (lg kH) increase linearly with the E parameters of the hydride-accepting tritylium ions 5 a,c–e (Figure 5). As tritylium ions (Ar3C + ) have previously been shown to be reliable reference electrophiles for characterizing the hydride donating abilities of BH, SiH, SnH, and CH hydride donors,[28] the correlations in Figure 5 enable us to characterize the hydride donor ability of the anions 1 a–c according to Equation (1). The resulting nucleophile-specific reactivity parameters N and sN are included in Figure 5. A different behavior was observed for combinations of carbanions 1 a and 1 c with tritylium ions of higher Lewis acidity, that is, for hydride transfer reactions from 1 a,c toward carbocations 5 f,g with an electrophilicity parameter E > 2 (or pKR + < 2). The UV/Vis spectroscopic monitoring of the reaction of the carbanion 1 a with the trimethyl-substituted tritylium (Figure 6 a) showed an instantaneous and quantitative disappearance of the absorbance at lmax = 450 nm owing to the rapid consumption of the tritylium ion 5 g immediately after mixing with 1 a (< 1 s), which was followed by a slow monoexponential increase of an absorption band at l = 450 nm that could be assigned to the unsaturated product 2 a. Fitting the function At = A0[1exp(kobs t)] + C to the curve in Figure 6 b gave a first-order rate constant of kobs = 5.49 102 s1 that did not depend on the concentration of the hydride donor 1 a, as demonstrated by the horizontal correlation line in Figure 6 c. Chem. Eur. J. 2014, 20, 1 – 10
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Figure 4. a) Hydride transfer from 1 a to 5 b in acetonitrile. b) Time-dependent UV/Vis spectra during the reaction of 5 b (lmax = 525 nm, c0 = 4.02 105 m) with 1 a (colorless, c0 = 4.84 104 m) in acetonitrile at 20 8C. c) Exponential decay of the absorbance, A, at 525 nm during the reaction of 1 a (4.84 104 m) with 5 b (4.54 105 m). d) Linear correlation of the first-order rate constants, kobs [s1], with the concentrations of 1 a with a slope corresponding to the second-order rate constant, kH [m1 s1].
The first-order rate constants for hydride transfer (kobs) from 1 a to 5 f,g as well as for the analogous reactions of 1 c with 5 f,g are collected in Table 6. The fast initial decay of the carbocation’s absorption and the independence of the rate constant for the formation of the unsaturated compound 2 a (or 2 c) of the concentration of the carbanion 1 a (or 1 c) is rationalized by the mechanism shown in Scheme 5. A fast but reversible oxygen attack of the highly Lewis acidic carbocations 5 at 1 leads to the quantitative formation of the colorless tritylated enol ethers 7. The backward reaction of 7 to 5 and 1 provides small concentrations of the hydride acceptor 5, which slowly oxidizes 1 (in excess) to form the hydride transfer products 2 and 6 that were observed by 5
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Full Paper Table 6. Second-order rate constants (kH) for the hydride transfer from the carbanions 1 a–c to the tritylium ions 5 a–g and first-order rate constants (kobs) for the formation of 2 (20 8C, MeCN). Carbanions[a] 1 a (R = NMe2)
1 b (R = OMe)
1 c (R = H)
Ar3C + [b] 5a 5b 5c 5d 5f 5g 5b 5c 5d 5e 5c 5d 5e 5f 5g
kH [m1 s1]
kobs [s1]
3 [c]
2.70 10 1.30 101 [c] 2.49 101 [d] 1.79 102 [d] 4.67 102 [c] 5.49 102 [c] 1.45 102 [d] 5.88 102 [d] 3.19 101 [d] 9.17 101[d] 1.74 102 [d] 1.12 101 [d] 3.64 101 [d] 7.59 103 [e] 7.67 103 [e]
[a] Counterion: K + . [b] Counterion: BF4 . [c] Derived from the increasing absorption of 2 a. [d] Derived from the decreasing absorption of the tritylium ion 5. [e] Derived from the increasing absorption of 2 c.
Figure 6. a) Time-dependent UV/Vis spectra of the reaction between 5 g–BF4 (c0 = 9.47 105 m) with 1 a-K (c0 = 3.38 103 m) in acetonitrile at 20 8C. b) Instantaneous fading followed by a slow increase of the absorbance, A, at 450 nm during the reaction of 5 g (c0 = 9.47 105 m) with 1 a (c0 = 3.38 103 m). c) Independence of the first-order rate constant of the concentration of carbanion 1 a.
Figure 5. Correlations of the second-order rate constants, lg kH, for the hydride transfer from the carbanions 1 a–c to the tritylium ions 5 in acetonitrile at 20 8C with the empirical electrophilicity parameters, E, of 5.
Scheme 5. Kinetically and thermodynamically controlled products of the reactions of carbanions 1 with the tritylium ions 5.
1
H NMR (Table 5) as well as by UV/Vis spectroscopy (Figure 6 a, b). According to Scheme 5, the decay of the concentration of 5 and the increase of the concentration of 2 follow the rate laws in Equations (2) and (3), respectively. Based on the UV/Vis spectroscopic monitoring of the reaction (Figure 6 a, b), we conclude that the attack of the highly Lewis acidic tritylium ions 5 at the oxygen of carbanions 1 to give the trityl enol ether 7 is much faster than the competing hydride transfer (kO @ kH). Owing to the negligible remaining concentrations of free carbocations 5, we can assume a quasi-stationary concentration of the tritylium ion 5 in the second phase of the reaction (d[5]/dt = 0), which allows us to rearrange Equations (2)–(4). Combination of Equation (3) with Equation (4) results in Equation (5). According to Equation (5), the rate of formation of the unsaturated product 2 is independent of the carbanion con&
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centration [1], in agreement with the results shown in Figure 6 c.
d½5=dt ¼ k O ½1½5k O ½7 þ k H ½1½5
ð2Þ
d½2=dt ¼ kH ½1½5
ð3Þ
For d[5]/dt = 0 in the second part of the reaction (conversion of 7 to 2 and 6):
½1½5 ¼ ðk O ½7Þ=ðk O þ kH Þ 6
ð4Þ
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Full Paper d½2=dt ¼ ½7 ðk H kO Þ=ðk O þ kH Þ
provided unequivocal evidence for the formation of this product of O-attack, because the alternative structure arising by C5attack should show resonances for two methyl and only one carbonyl carbon (in analogy to adducts 4). The ratio [7 b]/[2 b] changed from initially > 98:2 to 92:8 within 2.5 h at 20 8C (see the Supporting Information). After being warmed at ambient temperature, the 1H resonances of 7 b had vanished completely and the resonances of the hydride transfer products 2 b and 6 h could be detected. Thus, the observations made by NMR spectroscopy mirror those made by photometry (Figure 6) and corroborate the mechanistic proposal in Scheme 5.
ð5Þ
For kO @ kH :
d½2=dt ¼ ½7ðk H kO Þ=k O ¼ ðk H =K O Þ½7
ð6Þ
Since kO @ kH, Equation (5) simplifies to Equation (6) and, because of the relation KO = kO/kO, finally yields kobs = kH/KO. Using the N and sN parameters of 1 a and 1 c from Figure 5 and the electrophilicities E of the tritylium ions 5 f and 5 g from Table 4 Equation (1) allows the calculation of the second-order rate constants kH for the hydride transfer reactions listed in Table 7 that gave kinetics for the formation of the arylidene Meldrum’s acids 2, which are independent of the concentration of the enolates 1. Equilibrium constants for the O-attack, KO, can then be derived for these enolate-carbocation combinations from the ratio kH/kobs (Table 7).
Table 7. Calculation of equilibrium constants for the O-attack (KO) from the experimental (kobs) and extrapolated (kH) hyride transfer rate constants. Carbanion
Ar3C +
kH[a] [m1 s1]
kobs[b] [s1]
KO [m1]
1 a (R = NMe2)
5f 5g 5f 5g
3.19 104 6.48 104 5.55 102 1.02 103
4.67 102 5.49 102 7.59 103 7.67 103
6.8 105 1.2 106 7.3 104 1.3 105
1 c (R = H)
[a] Calculated by substituting N (and sN) from Figure 5 and E from Table 4 into Equation (1). [b] From Table 6.
Scheme 6. Reversible formation of the O-adduct 7 b from 1 b and 5 h at 20 8C and its conversion to the final products 2 b and 6 h after being warmed to ambient temperature.
Since the substituent R is not in direct conjugation with the carbanionic center of 1, carbanion 1 a is only slightly more Lewis basic than 1 c. In agreement with their similar pKR + values (Table 4), the tritylium ions 5 f and 5 g possess similar Lewis acidities towards 1 a and 1 c. Though the reactions of 1 a,c with 5 f,g were thus postulated to quantitatively generate the corresponding adducts 7 at ambient temperature, the NMR spectroscopic characterization of species 7 was unsuccessful because of the fast subsequent conversion of 7 to the products of hydride transfer 2 and 6. As decreasing stabilization of the tritylium ion 5 can be expected to affect the equilibrium constants KO more than the rate constants kH, Equation (6) predicts a prolonged life time of adducts 7 when less stabilized tritylium ions are employed. Indeed, mixing of the parent tritylium tetrafluoroborate 5 h-BF4 with 1 b-K in CD3CN at ambient temperature resulted in the detection of a new species by 1H NMR spectroscopy that disappeared within minutes to produce the known resonances of the hydride transfer products 2 b and 6 h (Scheme 6). By lowering the reaction temperature to 20 8C, we finally succeeded in trapping the O-adduct 7 b formed by addition of the parent tritylium ion 5 h to the methoxy-substituted carbanion 1 b (Scheme 6). The life time of 7 b in CD3CN solution at 20 8C was sufficiently long to record 1H and 13C NMR spectra that Chem. Eur. J. 2014, 20, 1 – 10
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The appearance of an additional singlet at dH = 2.09 ppm, assigned to the formation of acetone (ca. 35 %), indicated that the pathway shown in Scheme 6 is accompanied by a subordinate second process. In accord with literature reports,[33] a retro-hetero-Diels–Alder reaction of 7 b might account for the formation of the traces of acetone. This side reaction is not shown in Scheme 6 as it does not affect the kinetics [Eqs. (2)– (6)] of the formation of the unsaturated arylidene Meldrum’s acids 2. Variation of X will have the same, but opposite effect on DG0 of the hydride abstraction from the carbanions 1 by any carbocation R + as on DG0 of the hydride addition to the benzylidene Meldrum’s acids 2. Yet, Scheme 7 shows that replacement of X = H by OMe retards the hydride addition about twotimes more than it accelerates the hydride abstraction, whereas replacement of X = OMe by NMe2 has a seven-times larger effect on the hydride addition than on the hydride abstraction. This trend corresponds to our previous observation that in hydride transfer reactions to carbocations, substituent effects in the hydride acceptors have a much greater impact on the 7
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Full Paper only be generated in such small equilibrium concentrations that they were not detectable. For this reason, it is possible to measure the second-order rate constants for the hydride abstractions from 1 by these carbocations. Since hydride abstractions by tritylium ions can be described by Equation (1), it is possible to calculate N and sN for the hydride donor abilities of 1 a–c and compare them with those of other hydride donors (Scheme 9). As the parameters N for the hydride donicities of 1 a–c are 8–10 units smaller than for their C-reactivities, benzhydrylium ions react exclusively with CC bond formation.
Scheme 7. Rate constants (at 20 8C) for hydride abstractions from 1 a–c by carbocations R + (kH, in MeCN, from Table 6) and hydride additions to benzylidene Meldrum’s acids 2 a–c (kadd, in dichloromethane, from ref. [38]).
rate constants of hydride transfer than the same substituent variation in the hydride donor (Scheme 8).[39] Our explanation that electron donors generally reduce the rate of the identity reactions and, therefore, reduce the hydride-accepting ability of the carbocation more than they increase the hydride-donating ability of the alkene[40] can analogously Scheme 8. Hydride transfer between carbocations and be employed to rationalize the unsaturated hydride donors. trends in Scheme 7. Scheme 9. Comparison of the hydride donating abilities of carbanions 1 a– c with those of various other CH, SiH, SnH, and BH hydride donors (in dichloromethane or acetonitrile if not mentioned otherwise, from ref. [28]).
Conclusion With nucleophilicity parameters 12 < N < 15, the 5-benzylsubstituted anions of Meldrum’s acid have similar nucleophilic C-reactivities as the anion derived from the parent Meldrum’s acid (Table 3), in line with previous observations that methyl groups at the carbanionic center of diethyl malonate or acetylacetonide anions have little effect on their nucleophilic reactivities.[9, 14] Obviously, C-nucleophilicity is much greater than the hydride-donating ability, as in none of the reactions of the carbanions 1 with the benzhydrylium ions 3 the formation of the hydride abstraction products 2 was observed. We have repeatedly mentioned that steric effects are not explicitly considered by Equation (1), which, therefore, cannot be used for reactions of bulky reagents (e.g., tritylium ions)[34, 35] though we have recently reported that Equation (1) is applicable to reactions of trityl cations with primary amines and hydride donors.[28, 34, 41, 42] Indeed, tritylium ions do not react with the anions 1 to form CC bonds. Highly reactive tritylium ions react with the oxygen of the anions 1 to give trityl enol ethers, which subsequently decompose with formation of the hydride transfer products 2 and 6 and, to a minor extent, by retrohetero-Diels–Alder pathways.[33] In contrast, the Lewis acidities of the dimethoxy and better donor-substituted tritylium ions 5 a–e are so low that the intermediate trityl enol ethers 7 can &
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Experimental Section Study of C reactivity The kinetics of the reactions of the carbanions 1 with the benzhydrylium ions Ar2CH + (3) were followed photometrically at or close to the absorption maxima of Ar2CH + by using stopped-flow UV/Vis spectroscopy. The pseudo-first-order rate constants kobs [s1] were obtained by least-squares fitting of the decaying absorbance of Ar2CH + to the monoexponential function At = A0 exp(kobs t) + C. The second-order rate constants kC [m1 s1] were then obtained from the slopes of the linear correlations of kobs with the concentrations of the carbanions.
Study of hydride transfer rates The reactions of the carbanions 1 with the triarylmethylium ions Ar3C + (5) were followed photometrically at or close to the absorption maxima of either 5 or the benzylidene Meldrum’s acids 2 by using conventional or stopped-flow UV/Vis spectroscopy. The pseudo-first-order rate constants kobs [s1] were obtained by leastsquares fitting of the decaying absorbance of 5 to the monoexponential function At = A0 exp(kobs t) + C or of the increasing absorbance of the unsaturated products 2 to the monoexponential func-
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Full Paper tion At = A0·[1exp(kobs t)] + C. The second-order rate constants kH [m1 s1] were then obtained from the slopes of the linear correlations of kobs with the concentrations of the carbanions. The kobs of the formation of 2 a and 2 c through the reactions of tritylium ions 5 f,g with carbanions 1 a and 1 c, respectively, were found to be independent of the concentrations of the carbanions. For further details, see the Supporting Information.
[25] [26]
Acknowledgements Financial support by the Deutsche Forschungsgemeinschaft (SFB 749, project B1) is gratefully acknowledged. We thank Dr. Peter Mayer (LMU Mnchen) for determining the X-ray crystal structure of 4 af.
[27]
[28]
Keywords: alkylation · ambident reactivity · carbocations · kinetics · linear free energy relationships
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Received: April 18, 2014 Published online on && &&, 0000
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FULL PAPER & Ambident Reactivity
Several options: Carbocations react with the anions of 5-benzylated Meldrum’s acids by attack at the enolate carbon or oxygen or through hydride abstraction (see illustration). Kinetic studies with benzhydrylium and tritylium ions reveal the preferred pathways.
X. Chen, Y. Tan, G. Berionni, A. R. Ofial,* H. Mayr && – && Di- and Triarylmethylium Ions as Probes for the Ambident Reactivities of Carbanions Derived from 5Benzylated Meldrum’s Acid
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Chem. Eur. J. 2014, 20, 1 – 10
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2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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