A-PDF Split DEMO : Purchase from www.A-PDF.com to remove the watermark Figure 7.5 (a) Transition state for E2H-syn elimination. (b) Transition state for E2H-anti elimination. (c) Transition state for E,C elimination. tion state similar to that shown in Figure 7.5~is expected, since base attacks the molecule backside to the leaving group but frontside to the /3 hydrogen. Let us now turn to the experimental results to see if these predictions are borne out in fact. It has long been known that E2H reactions normally give preferentially anti elimination. For example, reaction of meso-stilbene dibromide with potassium ethoxide gives cis-bromostilbene (Reaction 7.39), whereas reaction of the D,L-dibromide gives the trans product (Reaction 7.40).lo2 A multitude of other examples exist-see, for example, note 64 (p. 355) and note 82 (p. 362). E2H reactions do, however, give syn elimination when: (1) an H-X di- hedral angle of 0" is achievable but one of 180" is not or, put another way, H and X can become syn-periplanar but not trans-periplanar ; (2) a syn hydrogen is much more reactive than the anti ones; (3) syn elimination is favored for steric reasons; and (4) an anionic base that remains coordinated with its cation, that, in turn, is coordinated with the leaving group, is used as catalyst. The very great importance of category 4 has only begun to be fully realized in the early 1970s. lo2 P. Pfeiffer, 2. Physik. Chem. Leibrig, 48, 40 (1904). 1,2-Elimination Reactions 371 An example of category 1 is found in the observation by Brown and Liu that eliminations from the rigid ring system 44, induced by the sodium salt of 2- cyclohexylcyclohexanol in triglyme, produces norborene (98 percent) but no 2-de~teronorbornene.~~~The dihedral angle between D and tosylate is O", but Crown ether present: No Yes that between H and tosylate is 120". However, when the crown ether (45), which is an excellent complexing agent for sodium ion, is added to the reaction the amount of syn elimination drops to 70 percent (the sodium ion fits into the center of the crown ether molecule). Apparently, coordination of the sodium ion to both the leaving group and the base in the transition state, as in 46, is responsible for some of the syn elimination from 44 in the absence of crown ether (category 4 above) .Io4 OTs Category 2 is exemplified by E, elimination from 47, in which the tosylate group can become periplanar with either H, or H,. However, H, is activated and lo3 H. C. Brown and K.-J. Liu, J. Amer. Chem. Sac., 92, 200 (1970). lo4 R. A. Bartsch and R. H. Kayser, J. Amer. Chem. Sac., 96, 4346 (1974). When the leaving group is positively charged, reduced ion pairing reduces the amount of syn elimination: J. K. Borchardt and W. H. Saunders, J. Amr. Chem. Sac., 96, 3912 (1974). H, is not; when treated with potassium t-butoxide in t-butanol at 50°C, elimina- tion of HI is greatly preferred.lo5 However, when the crown ether, 48, is added, the amount of syn elimination is reduced. The results shown below are obtained. Again coordination of the cation must be partially responsible for the syn elimi- nation.lo8 Product of Elimination from 47 SOURCE:From R. A. Bartsch, E. A. Mintz, and R. M. Parlrnan, J: Am.Ch. Soc., 96, 4249 (1974). Reprinted by permission of the American Chemical Society. The role of steric factors in determining the synlanti ratio has been investi- gated by Saunders and co-workers. From experiments with deuterated substrates they calculated that formation of 3-hexene from t-pentoxide-catalyzed decom- position of 3-n-hexyltrimethylammonium iodide (49) proceeds 83 percent by syn and 17 percent by anti elimination. They also found that syn elimination gives almost entirely trans olefin, but anti elimination gives cis product, a phenomenon noted previously and called the syn-anti dichotomy. Saunders proposed that the reason for the small amount of anti elimination is that the bulky trimethyl- ammonium group forces the terminal methyl groups on the n-hexyl moiety as far away from it as possible, and thus hinders approach to an anti hydrogen. (The two staggered rotamers of 49 in which one hydrogen is anti are shown in 49a and 49b.) The anti hydrogen is less hindered in 49b, so that the anti elimination that does take place gives cis olefin. The major pathway, syn elimination, could occur from rotamers 49a, 49b, or 49c, but syn elimination from 49b or loss of HI from 'OK C. H. DePuy, R. D. Thurn, and G. F. Morris, J. Amcr. Chern. Soc., 84, 1314 (1962). lo6 R. A. Bartsch, E. A. Mintz, and R. M. Parlman, J. Arncr. Chcrn. Soc., 96, 4249 (1974). 1,2-Elimination Reactions 373 49c would cause the two alkyl groups to be eclipsed in the transition state. These are the two pathways for syn elimination leading to cis olefin. Syn elimination from 49a and loss of H, from 49c allows the two alkyl groups to be anti in the transition state. Therefore syn elimination gives trans olefin.lo7In accord with Saunders' theory, other bulky ammonium salts also show the syn-anti dichotomy, whereas unhindered ones appear to eliminate entirely anti.lo8 E,C reactions give entirely anti elimination. This fact seems to be universal, and the need for anti elimination is ,even more important than formation of the most stable product.log. 11° Thus, for example, 50 with N(Bu),Cl gives > 99.9 percent 51, whereas the other diastereomer, 52, gives > 99.9 percent 53.ll1 Of course, 51 is the more stable olefin. Because of the greater acidity of a vinylic than an alkyl proton, vinyl halides, RHC=CRX, are more likely than alkyl halides to undergo E,cB elimination. However, when the proton is not rendered even more acidic by a vicinal electron-withdrawing group, and when the basic catalyst is not too strong, E, reaction obtains. Then anti elimination is much the preferred pathway. loT D. S. Bailey and W. H. Saunders, Jr., J. Amer. Chem. Soc., 92, 6904 (1970). lo8 D. S. Bailey, F. C. Montgomery, G. W. Chodak, and W. H. Saunders, Jr., J. Amer. Chem. Soc. 92, 6911 (1970). log See (a) note 86, p. 364; (b) note 95, p. 368. ' "O G. Biale, A. J. Parker, S. G. Smith, I. D. R. Stevens, and S. Winstein, J. Amer. Chem. Soc.. 92, 115 (1970). ll1 See note 95, p. 368. Thus, for example, 54 gives entirely 55 when treated with NaOMe in methanol, but under the same conditions 56 gives only the allene 57.112 CHdCHz)z\ ,,Br NaOMe /C=C A CH3(CH2),CGC(CH~)~CH~ \ MeOH H (CH2)2CH3 (7.44) CH3(CH2)2\ /CH2CH2CH3 NaOMe /C ==C CH3(CH2)2C=C=CHCH2CH3 \ MeOH H Br I H (7.45) 56 57 The substrate /3-Alkyl substituents affect the rate of E2 eliminations differently depending on the leaving group. In ammonium and sulfonium salts they have little effect (but generally decrease the rate slightly), whereas in halides and tosylates they usually increase the rates.l13 These facts can be readily accommodated by the Winstein-Parker spectrum of transition states. The leaving group in an 'onium salt is relatively poor and strongly electron-withdrawing. Therefore eliminations from such compounds lie toward the E2H end of the spectrum and /3-alkyl groups, which decrease the acidity of the /3 hydrogen, decrease the rate of elimination. Eliminations from halides and tosylates lie farther toward the E,C end of the spectrum, in which the double bond is more well developed. Since alkyl groups increase the stability of a double bond, sub- stituents increase the rate of these reactions. a-Alkyl substituents have little effect on E,H-type reactions. However, they increase the rate of E2C-type reactions-again presumably because of the stabilizing effect of the alkyl group on the incipient double bond in the transition state.l14 In terms of hard and soft acid-base theory, it might also be said that alkyl substituents on the carbon make that carbon a softer acid and thereby render it more susceptible to attack by a soft base. Thus 58 reacts approximately 250 times faster than 59 with N(Bu),C1.115 CH3 CH3 I I CH3-C-CH3 CH3-C-H I I The leaving group The relative reactivity of a leaving group in an E2 elimination depends on where, in the spectrum of transition states, the transition state of the particular reaction lies. If the reaction is very E2C-like, the reactivities 112 S. W. Staley and R. F. Doherty, J. Chem. SOG.,D, 288 (1969). 113 See note 82, p. 362. 114 See note 86, p. 364, and note 95, p. 368. 116 See note 95, p. 368. 1,2-Elimination Reactions 375 -5 -4 - 3 -2 log kJ Figure 7.6 Response of rates of elimination of HX (log kE) and substitution (log k,) of cyclohexyl X, induced by NBu,CI in acetone containing lutidine at 75OC, - to change of leaving group X. From P. Beltrame, G. Biale, D. J. Lloyd, A. J. Parker, M. Ruane, and S. Winstein, J. Amer. Chem. Soc., 94, 2228 (1972). Reprinted by permission of the American Chemical Society. of the leaving groups correlate very well with their corresponding reactivities in the S,2 reaction. For example, Figure 7.6 shows such a correlation between the i rate of elimination of HX from cyclohexyl X by C1- and the rate of bimolecular substitution of X in cyclohexyl X by C1-.