2298
J . Org. Chem. 1990,55, 2298-2303
This compound was synthesized from l b (90%): mp 88-90 "C (ether); [ a ] D -183" ( c 0.80, CHCI,); IR (KBr) 2930, 1460, 1430, 1175,1130,1060cm-'; MS m/z 438 (M+ + l),437 (Mt), 380 (100), 117 (51), 73 (95). Anal. Calcd for Cz1H3,O3NS,Si: C, 57.63; H , 7.14; N, 3.19; S, 14.65. Found: C, 57.90; H, 7.23; N, 2.99; S, 14.35. Methyl 2,3,4-Trideoxy-6-0-(tert -butyldimethylsilyl)-2S - (2-benzot hiazolyl)-2-thio-a-~threo -hex-3-enopyranoside (4b). This compound (85%)was synthesized from Id: [ a ] D -23" (c 0.9, CHC13);IR (film) 2940, 2860, 1465, 1430, 1255, 1115, 1060 cm-';MS m / z 424.4 (Mt + 1),423.4 (Mt),366 (67),73 (100). Anal. Calcd for C,oH2903NSzSi: C, 56.70; H, 6.90; H , 3.31; S, 15.14. Found: C, 56.90; H, 7.02; N, 3.27; S, 14.98. General Procedures for the Reaction of (Allyloxy(thi0))benzothiazole Derivatives with Organocopper Reagents. (A) The Grignard reagent was prepared in diethy ether (5 mL) from Mg (3.07 mmol) and Me1 (3.07 mmol). This solution was cooled to -30 "C, and CUI (1.5 mmol) was added in one portion under argon. Stirring was continued during 30 min a t -30 "C, and then a solution (15 mL) of the substrate (1.06 mmol) in ether was added; the mixture was allowed to warm slowly to room temperature and stirred for 6 h. The reaction was diluted with diethyl ether and treated with concentrated aqueous NH4C1and a few drops of NH,OH, while vigorously stirring, to obtain a green suspension in a blue aqueous solution. The two layers were separated, and the ethereal phase was filtered and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was directly desilylated with tetrabutylammonium fluoride (4 mmol) in T H F (20 mL). After 2 h a t room temperature, the mixture was diluted with diethyl ether (20 mL) and washed with water (10 mL). The organic layer was dried (MgS04) and evaporated. Column chromatography of the residue (hexane-ethyl acetate, 7:3) yielded the product. (B) CUI (1.5 mmol) was added to a solution of the substrate (1.06 mmol) in diethyl ether (15 mL) a t 0 "C under argon. After 30 min the Grignard reagent (3.07 mmol), prepared in E t 2 0 , was then added dropwise with stirring. After 1 h the reaction was worked up as above. Identical procedures were followed by changing diethyl ether
to THF, stoichiometric amounts of CUIto catalytic amounts (5701, and IMgCH, to MeLi. We also tested the effect of substituting CUI by CuBr. In no case these changes have an appreciable effect on the final products. Ethyl 2,3,4-Trideoxy-%-C-methyl-a-~-erythro -hex-3-enopyranoside (3a). This compound was synthesized from 2a (68%): ["ID +21.9" (c 0.42, CHCl,); IR (film) 3435,2975,1660, 1455 cm-'. Anal. Calcd for CgH1603: C, 62.77; H , 9.36. Found: C, 62.93; H , 9.45. Ethyl 2,3,4-Trideoxy-2-C-methyl-a-~threo -hex-3-enopyranoside (3b). This compound was synthesized from 2b (70%): ["ID +194" (C 0.3, CHCl3); IR (film) 3440,2980,2880,1660,1455, 1370, 1190, 1115 cm-l. Anal. Calcd for C9Hl6O3:C, 62.77; H, 9.36. Found: C, 62.86; H , 9.48. Methyl 2,3,4-Trideoxy-4-C-methyl-a-~-erythro -hex-2-enopyranoside (5a). This compound was synthesized from 4a (68%): ["ID +89.2" ( c 0.42, CHCI,); IR (film) 3430, 2970, 1660, 1400,1185,1100 cm-'. Anal. Calcd for C8HI4O3:C, 60.74; H, 8.92. Found: C, 60.87; H , 8.97. Methyl 2,3,4-Trideoxy-4-C-methyl-a-~-threo -hex-2-enopyranoside (5b). This compound was synthesized from 4b (72%): [ ( ~ ] ~ - 1 0 . 9(C"0.25; CHCl,); IR (film) 3430,2970,1660,1400,1120 cm-'. Anal. Calcd for CBHI4O3:C, 60.74; H, 8.93. Found: C, 60.95; H, 9.05.
Acknowledgment. Financial support from CICYT and a Caja d e M a d r i d scholarship to A.M.G. a r e gratefully acknowledged. Thanks are expressed to Prof. P. Rollin (Universite d'orleans) for sending us information regarding the cross-coupling reaction and preparation of an analogue of 2b. Registry No. la, 23339-15-3; lb, 58888-62-3; IC, 51385-38-7; Id, 124944-63-4;2a, 124944-64-5;2b, 124944-65-6;3a, 124944-68-9; 3b, 124944-69-0;4a, 124944-66-7;4b, 124944-67-8;5a, 124944-70-3; 5b, 124944-71-4; tri-0-acetyl-D-glucal, 2873-29-2; methyl 2,6-di0-benzoyl-a-D-glucopyranoside, 26927-44-6; 2-chlorobenzothiazole, 615-20-3: 2-mercaptobenzothiazole, 149-30-4.
Solvation and Steric Effects on Electrophilic Reactivity of Ethylenic Compounds. 1. Stereochemistry and Bromination of Congested Adamantylidenealkanes Marie-Franqoise Ruasse,* Shahrokh Motallebi, Bernard Galland, and John
S. Lomas
Institut de Topologie et de Dynamique des Systdmes de l'liniversitd Paris 7, associt? a u CNRS, I , rue Guy de la Brosse, 75005 Paris, France Received May 9, 1989 In order to evaluate the dependence of the steric effects of alkyl groups on the crowding of the double bond, bromination rate constants of adamantylidenealkanes 1, Ad=CRR with R = H or Me and R' = H, Me, i-Pr, t-Bu, or neo-Pe, and similarly substituted isopropylidenealkanes 2, Me2C=CRR', are compared. Since the bromination rate of l a (R = R' = H) is that expected by considering only the polar effect of two gem-isopropyls, the adamantyl group in 1, like the gem-methyls in 2, clearly does not exhibit any intrinsic steric effect. However, branched substituents R slow the reaction of 1 twice as much as that of 2. This difference between the effects on 1 and 2 does not arise from differences in the stereoarrangement of R and R since, according to MM2 calculations, they adopt exactly the same conformation in both alkene series. Comparison of the bromination rates of 1 in methanol with those measured in acetic acid reveals that the solvent effect ( k M e O H / k A c O H about 4) is markedly smaller than that (kMeOH/kAdH = 25) on linear alkenes, which suggests that greater steric retardation in adamantylidenealkanes can be attributed to mechanistic changes: inhibition of nucleophilic solvent assistance in the ionization step and/or return resulting from a slow product-forming step.
That t h e r e is n o general m e t h o d of describing steric effects q u a n t i t a t i v e l y severely limits t h e scope of s t r u c 0022-3263/90/1955-2298$02.50/0
ture-reactivity relationships for t h e quantitative analysis a n d prediction of reactivity data, as well as for the un-
C 1990 American Chemical Society
Electrophilic Reactivity of Ethylenic Compounds
J . Org. Chem., Vol. 55, No. 8, 1990 2299
derstanding of mechanisms.'S2 Neither the earlier approaches based on steric parameter ~ c a l e snor ~ * more ~ recent methods such as force field c a l c u l a t i o n ~or~ ~topo~ logical treatments2y5 give satisfactory results over wide reactivity ranges. Most of the difficulties arise from the fact that, because of nonbonded interactions which vary along the reaction pathway, kinetic steric effects are not additive. Among the numerous reactions whose sensitivity to steric effects has been investigated, electrophilic addition to olefins is of particular interest since up to four branched substituents can interact mutually and with the entering electrophile.6 It is well known, for example, that steric effects considerably retard the bromination of alkenes with branched alkyl substituent^.^,^ The rate reduction is noticeable, even when the double bond bears only one moderately bulky group: 3-methyl-l-butene, iPrCH=CH,, reacts in methanol 1.7 times more slowly than l - b ~ t e n e . ~ The effect is significantly more important in tetrasubstituted alkenes? from 2,3-dimethyl-2-butene, Me2C=CMez, to 2,3,4-trimethyl-2-pentene, iPrMeC=CMez, the rate falls by a factor of 9. The limit, where steric effects totally inhibit any reaction of the double bond with bromine, is reached for alkenes which do not appear very highly congested, such as tetraisobutyl-9or tetraisopropylethylene.lo Not only steric but also polar effects of alkyl groups contribute to the bromination rates." The additive polar contribution is easily determined by the previously established equation', (eq 1) where log k, is 6.89 in metha(log k)poi = -3.03CU* + 0.43d + log k, (1) no1,12 13.8 in water,13and 5.51 in acetic acid,14 and d = 1 for gem-disubstituted and trisubstituted alkenes and d = 0 for the others. The steric contribution6 can then be estimated from the difference between the experimental rate constant and that predicted by eq 1. Numerous attempts have been made to analyze the steric effects on bromination rates quantitatively by various methods, in particular, steric parameter scales which work more or less satisfactorily for alkenes involving only one bulky subs t i t ~ e n t . Relationships ~,~ valid for limited sets of data have thus been obtained. For example, Grosjean et al. found for the reactivity of 15 tetrasubstituted alkenes a fairly good correlation with Hancock's E,' (eq 2), erroneously suggesting that poiar effects are negligible in the bromilog k = 1.29EE,'
+ 6.32
(2)
(1) Shorter, J. Correlation Analysis of Organic Reactivity; Research Studies Press, Wiley: New York, 1982. Shorter, J. Advances in Linear Free Energy Relationships; Chapman, N. B., Shorter, J., Eds.; Plenum Press: London, 1972; p 71. (2) (a) Gallo, R. Progr. Phys. Org. Chem. 1983, 14, 115. (b) Hunger, S. H.; Hansch, C. Ibid. 1976, 12, 91. (3) (a) Taft, R. W., Jr. Steric Effects in Organic Chemistry; Newman, M. S., Ed.; Wiley: New York, 1956. (b) Charton, M. Progr. Phys. Org. Chem. 1973, 10,81. (4) (a) Allinger, N. L. Adv. Phys. Org. Chem. 1975, 13,1. (b) Boyd, D. B.; Lipkowitz, K. B. J . Chem. Ed. 1982, 59,269. (c) Lomas, J. S. L'actualitB Chimique 1986, May, 7. ( 5 ) (a) Balaban, A. T.; Chiriac, A.; Moto, I.; Simon, Z. Quantitative Fit in QSAR; Lecture Notes No. 15, Springer: Berlin, 1980. (b) Dubois, J. E.; Panaye, A,; Vieillard, A. New J . Chem. 1981, 371. (6) Ruasse, M. F.; Argile, A,; Bienvenue-Go&, E.; Dubois, J. E. J. Org. Chem. 1979,44, 2758. (7) Dubois, J. E.; Mouvier, G. Bull. SOC.Chim.Fr. 1968, 1426, 1441. (8) Grosjean, D.; Mouvier, G.; Dubois, J. E. J. Org. Chem. 1976, 41, 3872. (9) Andersen, L.; Berg, U.; Petterson, I. J . Org. Chem. 1985,50, 493. (10) Langler, R. F.; Tidwell, T. T. Tetrahedron Lett. 1975, 777. (11)Dubois, J. E.; Bienvenue-Goetz, E. Bull. SOC.Chim.Fr. 1968, 2094. (12) Bienvenue-Goetz, E.; Dubois, J. E. Tetrahedron 1978,34, 2021. (13) Bienvenue-Goetz, E.; Dubois, J. E. Tetrahedron 1968,24, 6777. (14) Ruasse, M. F.; Zhang, B. L. J . Org. Chem. 1984, 49,3207.
Table I. Rate Constants" for Free Bromine Addition to Adamantylidenealkanes 1 in Methanol and in Acetic Acid at 25 'C k.b M-'s-' 1 R R' MeOH AcOH 4.2 x 105 4.8 x 104 a H H 1.6 X lo6 b H Me C Et 1.2 x 106 H H i-Pr d 8.3 x 104 e H t-Bu 1.6 x 103 7.0 X lo2 9.1 x 103 f H neo-Pe 8.2 x 106 Me Me 2.5 x 107 g h Et Et 2.9 X lo6 i Me i-Pr 5.7 x 105 1.9 x 105 i-Pr i-Pr C c j Obtained by extrapolation to zero bromide ion concentration from measurements in the presence of sodium bromide (methanol) or lithium bromide (acetic acid). bTo *4%. CNoreaction.
nation of these olefins.8 The failure of the Taft type analysis is not unexpected since interactions between the entering bromine and the double bond substituents are probably the main rate-controlling factors. A rational approach to understanding steric effects on electrophilic addition should, therefore, be based on a stereochemical analysis of branched alkenes in order to identify the most favorable conformations for electrophilic attack and, then, to estimate their stabilities and the rotational barriers for conformational exchange. Unfortunately, experimental data on this topic, which calls for dynamic NMR and crystallography, are scarce;15aempirical force field calculations are more accessible15b but have mainly been applied to highly congested alkenes, tetraisopropy1ethylenel6 or the elusive tetra-tert-butylethylene,17which do not react with bromine. Recently, the static and dynamic stereochemistry of five alkenes bearing four primary alkyl groups has been investigated experimentally and the~retically.~These first results are of interest; for example, a barrier of 8.6 kcal mol-' to the rotation of one isobutyl group has been measured in solution, in agreement with the MM2 calculated value. It is, however, too early to apply this method extensively to the interpretation of the numerous olefin bromination data. T o tackle this problem more simply, we chose to investigate the electrophilic bromination of conformationally locked alkenes 1, derived from methylideneadamantane, la. The adamantyl cage, the tied-back equivalent of two eclipsed gem-isopropyl groups, is so inflexible that substituents R and R' are expected to adopt conformations probably different from and more constrained than those they have in acyclic isopropylidenealkanes 2 and 3. The comparison of the effect of the branched group R on the bromination rates of 1, 2, and 3 should give information as to the relationship between the conformation of R and the reactivity of the double bond toward bromine. Results Olefins la-h were synthesized from the corresponding tertiary alcohols18 obtained by the reaction of adamantanone and the appropriate organolithium reagents, according to classical procedures.19 l i and l j were prepared (15) (a) Rummens, F. H. A.; Lomas, J. S.; Tiffon, B.; Coupry, C.; Lumbroso-Bader, N. Org. Magn. Reson. 1982, 19, 35. (b) Ermer, 0.; Lifson, S. Tetrahedron 1974, 30, 2425. (16) Ermer, 0. Angew. Chem., Int. Ed. Engl. 1983, 95,998. (17) Lenoir, D.; Dauner, H.; Frank, R. Chem. Ber. 1980, 113, 2636. Farini, G.; Simonetta, M.; Todeschini, R. J. Comput. Chem. 1981,2,149. (18) Lomas, J. S.; Sagatys, D. S.; Dubois, J. E. Tetrahedron Lett. 1971, 599.
2300 J. Org. Chem., Vol. 55, No. 8, 1990
Ruasse et al.
R Me,C =C
‘R’
-1 a,
/R
R‘
2 -
Me$ = C
/Me \R,
’
3 -
R = R’ = H;b, R = H, R ‘ = Me; c, R = H, R ’ = Et; d, R = H, R’ = LPr; e, R = H,R’ = t-Bu; f, R = H, R‘ = neo-Pe; g, R = R’ = Me; h, R = Et, R = Et; i, R = Me, R’ = i-Pr; j, R = R = i-Pr
by the McMurry method.20 Rate constants, k , for free bromine addition to la-i in methanol and acetic acid are given in Table I; they have been obtained by extrapolating kinetic measurements carried out in the presence of added sodium bromide to zero bromide ion concentration.21s22 In protic solvents, bromination leads not only to the usual dibromide but also to solvent-incorporated products whose formation releases bromide ions. These latter react with bromine rapidly, forming tribromide ions, according to eq 3. Since Br,- is Br2 + BrBr3(3) an electrophilic species, two brominating agents coexist in the medium so that kinetic experiments carried out by following the overall bromine uptake give only composite rate constants related to both free bromine and tribromide ion additions. To simplify the situation, bromination is followed in the presence of bromide ions in excess with respect to alkene and bromine, thus keeping the ratio Br2/Br3-constant during the course of the reaction. The constants, k, for bromine addition and k g , - for tribromide addition, are then obtained from bromde ion effects on the experimental rate constants, keXp,by the following equation: kexp(l + K[Br-1) = k + KkB,,-[Br-] (4) where K is the constant of eq 3. The constants keXpa t several bromide concentrations and k and kBr,- calculated from eq 4 are given in Table SI (see supplementary material). kBlg-is not necessarily related to a single process since it can include not only the tribromide addition but also the bromide medium effect or free bromine addition assisted by bromide ion, these being kinetically indistinguishable p r o c e s ~ e s . ~Consequently, ~,~~ only constant k , which is unambiguously related to free bromine addition unassisted by bromide, is considered in the following discussion. In Table 11, the log k values for the reaction of acyclic alkenes 2 in methanol are presented with those of 1. The rate constants of 2, k,, , were previously obtained in methanol with 0.2 M adc!ed NaBr.24 The data reported here result from extended kinetic measurements, as described above, and correspond to the constants k for unassisted free bromine addition. Steric contributions6 of the branched substituents R and R’ to the bromination rates of alkenes 1 and 2 in methanol are also given in Table 11. They have been estimated by subtracting the polar contributions (calculated by eq 1) from the experimental data. In Table I11 are collected the rate data8 and the steric contributions of tetrasubstituted alkenes, 3. (19) Molle. G.: Briand. S.:Bauer. P.: Dubois. J. E. Tetrahedron 1984. 40, 5113. (20) McMurry, J. E.;Fleming, M. P.; Kees, K. L.; Krepski, L. R. J. Org. Chem. 1978,43, 3255. (21) Bartlett, P. D.; Tarbell, D. S. J . Am. Chem. SOC.1936, 58, 466. (22) Bienvenue-Goetz, E.; Dubois, J. E. Bull. SOC.Chim. Fr. 1968, 2089. (23) Dubois, J. E.; Huynh, X. Q. Tetrahedron Lett. 1971, 3369. (24) Grosjean, D.; Mouvier, G.; Dubois, J. E. J. Org. Chem. 1976, 41, 3869.
It has been observed that, in methanol, bromine does not add to alkene lj, the semi-tied-back analogue of tetraisopropylethylene. This result is not unexpected in view of the inertness of the highly crowded tetraneopentylethylenez5 and tetraisopropylethylene toward this electr~phile.~ Molecular mechanics calculations (MM2 program) have been performed on alkenes 1 and 2. For none of these is any distorsion of the ethylenic double bond plane observed. The most relevant geometrical feature of these alkenes is a noticeable pinching of the ethylenic bond angles. In 1, and in 2 as well, the angle RCR’ between the substituents and that between the bonds involved in the adamantyl cage or between the two methyls of 2 is in the 112-115’ range; it is as small as 111’ in the case of the highly congested li and 2i. This angle pinching is not associated with a significant C=C nor =C-C bond elongation. Strain energies and some relevant dihedral angles are shown in Tables IV and V, respectively (data for the whole set of alkenes are given in Table SIV, supplementary material).
Discussion Tetraisopropylethylene Analogues. The different behavior toward bromine of the three tetraisopropylethylenes, either non-tied-back, 4, or semi-tied-back, lj, or totally tied-back adamantylideneadamantane, 5 , deserves comment. Molecular mechanics calculations on 4, which does not react with bromine, reveal16 a strong preference for the C2hconformation, a (barrier to the rotation of one isopropyl group is about 15 kcal mol-’). When two gem-isopropyls are locked as in lj, the stabler conformation becomes /3 but bromine attack is not easier. Finally, for 5 the sole conformation is y and the electrophilic reactivity toward bromine is partially restored;26 bromine adds to 5 in carbon tetrachloride, but the reaction stops a t the formation of the bromonium-tribromide ion pair27insoluble in this solvent. Nucleophilic attack on this bromonium ion, usually the product-forming step, is totally inhibited; dissolution of the ion pair in methanol leads to the starting reagents.
Q=
