5580
Memory Effects in Multiple Carbonium Ion Rearrangements. 111. The Effects of ,&Methyl Substitution on Selectivity and Reactivity in the Ring Expansions of 7-Norbornylcarbinyl and 7-NorbornenylcarbinylDerivatives1’2a-d Jerome A. Berson,2e Dennis S. Donald, and William J. Libbey Contribution from the Department of Chemistry, UniGersity of Wisconsin, Madison, Wisconsin 53706. Received March 29, 1969 Abstract: A methyl substituent at C-7, in the 6 position relative to the initial site of heterolysis, causes marked changes in the products of carbonium ion reactions in the 7-norbornylcarbinyl system. Under kinetically controlled conditions of deamination in glacial acetic acid, at room temperature, almost all of the ring-expanded product from 7-methylnorbornyl-7-carbinylamine is the once-rearranged tertiary acetate, 2-methylbicyclo[2.2.2]oct-2-yl acetate, 10-OAc. Doubly rearranged product of the l-methylbicyclo[3.2,1]oct-exo-2-yl structure, 8-OAc, is formed in acetolysis at 120 of the 7-methylnorbornyl-7-carbinyl p-bromobenzenesulfonate, but this is largely a product of thermodynamic control, resulting from the instability of the tertiary acetate under the solvolysis conditions. New syntheses of 7-methylnorborn-2-enyl-anti- and -syn-7-carbinyl derivatives (12 and 13) and of 1-methyltricyclo[3.2.1.02~7]oct-6-ylderivatives (26, 27, 32) are described. Ring expansions of the anti-7-carbinyl system might be expected to parallel those in the unmethylated series by giving products derived from l-methyltricyclo[3.2.1.O2t7]oct6-yl cation (L ’), but this cation is unstable and suffers “crossover” to the 1-methylbicyclo[3.2.lloctenyl allylic cation of the G ’ series. In the ring expansion of the syn system, the G ’ cation expected as the major product of double rearrangement is more stable. The difference in product distributions shows that even though the once-rearranged cation is tertiary, a memory effect persists in the twice-rearranged products of deaminative ring expansion. An important side reaction in the syn system is ring closure between the double bond and the syn-7-carbinyl side chain to produce l-methyltricyclo[3.3.0.02~7]octan-4-yl cation, which gives rise to five new products. Two of these are identified as the corresponding acetates by independent synthesis from l-methyltricyclo[3.3.0.0*~7]octan-4-one, for which a new synthesis is reported. Ratios of acetolysis rate coefficients at 120.4’ (roughly corrected for the direct displacement component) permit the evaluation of the effect of 6-methyl substitution. The ratio of rates (7-methyl/ unsubstituted) is 6.3 for the syn-7-carbinyl system, 3.3 for the anti-7-carbinyl one, and 10.6 for the saturated one. The latter figure is in close (but probably fortuitous) agreement with a ratio of about 11 deduced from values in the literature for the ratio of rates of 1methylcyclopentylcarbinyl and cyclopentylcarbinyl p-toluenesulfonates. O
M
emory effects in ring-expanding multiple rearrangements of norbornylcarbinyl (l),zb 2-norbornenylsyn-7-carbinyl (2),2a2-norbornenyl-anti-7-carbinyl (3),2a and 0 t h e r ~ ~ 3systems ~J manifest themselves as a preference for migration in the second rearrangement step by the group more remote from the site of heterolysis. A number of questions remain on the scope of such ef-
1
2
3
fects and their interpretation. One of the most important and most difficult of these concerns the nature of the species formed in the first rearrangement step. It has been convenient to formulate this as a true metastable intermediate, and indeed there is compelling evidence in somezd,abut not allZanbcases of memory effects that it (1) This work was supported in part by grants from the National Institute of Arthritis and Metabolic Diseases (AM-07505) and the Wisconsin Alumni Research Foundation. (2) For closely related studies, see papers I, 11, IV, and V in this series: (a) J. A. Berson, J. J. Gajewski, and D. Donald, J . A m . Chem. SOC.,91, 5550 (1969); (b) J. A. Berson, M. S. Poonian, and W. J. Libbey, ibid., 91, 5567 (1969); (c) J. A. Berson, D. Wege, G. M. Clarke, and R. G. Bergman, ibid., 91, 5594(1969); (d) J. A. Berson, R. G. Bergman, G. M. Clarke, and D. Wege, ibid., 91,5601 (1969). (e) Please address inquiries to this author at Sterling Chemistry Laboratory, Yale University, New Haven, Conn. 06520. (3) (a) J. A. Berson and P. Reynolds-Warnhoff, J . Am. Chem. Soc., 84,682 (1962); (b) ibid., 86,595 (1964); (c) J. A. Berson and D. Willner, ibid., 84, 675 (1962); (d) ibid., 86,609 (1964).
Journal of the American Chemical Society
91:20
can be intercepted by external nucleophiles before the second rearrangement step. This paper is the first of a series examining this transient intermediate further by experiments in which appropriate substitutions are made to control the rate of the second rearrangement step. In the present work, the strategy is to introduce a methyl group at C-7 of 1, 2, and 3, thereby making the product of the first rearrangement a tertiary cation and retarding the rate of the second rearrangement. Further studies will be reported soon on systems designed to accelerate the second rearrangement step by methyl substitution two carbons removed from the site of heterolysis. Ring Expansion of the 7-Methyl-7-norbornylcarbinyl System, 4. The profound modifying effect of methyl substitution becomes apparent immediately in the behavior of the 7-methyl-7-norbornylcarbinyl system, 4. The unmethylated analog, the 7-norbornylcarbinyl system, 1, gives ring-expanded products which are both singly ( 5 ) and doubly ( 6 ) rearranged, the memory effect being revealed by position labeling with deuterium.2b The cationic intermediate leading to bicyclo[2.2.2]octyl and to exo-bicyclo[3.2. lloctyl products 5 and 6 has positive charge at each of two secondary sites,-and nucleophilic capture occurs readily at each. In the 7-methyl series, 4, the first ring-expanded 2-methylbicyclo[2.2.2]oct-2-yl cation, 7,has most of the charge at one tertiary center, and capture in the doubly rearranged l-methylbicyclo[3.2.l]oct-exo-2-ylform, 9, should be much less favorable than in the unmethylated series. In practice, this bias could cause insuperable difficulties if it were
/ September 24, 1969
5581
born-2-enyl-syn-7-carboxylic acid (14 and 15) is obtained by direct methylation (sodium triphenylmethide, methyl iodide) of a mixture of the syn- and anti-unmethylated esters 16. The anti-carbomethoxy compound 14 predominates by 8 :I in the mixture, which can be separated
1
COZCH, 1
6
5
6
u
16
14
4
8
strong enough to preclude formation of doubly rearranged product 8. The acetolysis of 7-methylnorbornyl-7-carbinyl p-nitrobenzenesulfonate (4-OBs) at 100" does in fact give some of the twice-rearranged secondary acetate 8-OAc. In addition to the 11.7x of this material, there are 59.1 % of unrearranged primary acetate 4-OAc, 15.5 % of once-rearranged tertiary acetate 10-OAc, and 3.6 % of the product, 11-OAc, resulting from methyl shift. CH,-OAc
d-57 10
CH3CH2yOAc
& 11
This encouraging result is deceptive, however, for it is quite likely that the desired twice-rearranged product 8-OAc is an artifact arising from the instability (established by control experiments) of the tertiary acetate 10 under the solvolysis conditions. Further, under the milder conditions of deamination of 4-NH2(room temperature, glacial acetic acid), none of the doubly rearranged product 8-OAc is formed. Ring expansion is very efficient, but the rearrangement stops sharply after the first step, giving 90 % of once-rearranged material (82% 10-OAc, 8 % 10-OH). The remainder of the product is unrearranged primary material 4-OAc. These results preclude the examination of the memory effect in the saturated 7-methyl compounds 4 and shift attention to the unsaturated series. The starting materials and most of the anticipated products of this study are not reported in the literature, and a number of syntheses and stereochemical assignments must be made before the ring expansion work can begin. Synthesis of the syn- (and anti-) 7-Methylnorborn-2enyI-anti- (and -syn-) 7-carbinyI Systems (12 and 13). A mixture of the methyl esters of syn-7-methylnorborn2-enyl-anti-7-carboxylic acid and anti-7-methylnor-
15
by preparative vapor chromatography (vpc). The stereochemical assignments to 14 and 15 rest upon an unambiguous alternate synthesis of the syn-carbinol, 13-OH (Scheme I). anti-7-Methyl-exo-2-hydroxynorbornane-syn-7-carboxylic acid lactone (17)4 is reduced to the diol 18, which readily forms a di-p-toluenesulfonate 19, together with variable amounts of the ether 19a. Potassium t-butoxide in t-butyl alcohol converts 19 to the unsaturated p-toluenesulfonate 13-OTs, admixed with 3-methylnortricyclyl-3-carbinyl p-toluenesulfonate (20-OTs) in the approximate ratio 4 : 1 13-OTs-20-OTs. The mixture of p-toluenesulfonates is reduced by lithium in liquid ammonia5 to a mixture of the corresponding alcohols, 13-OH and 20-OH, which are separated by vpc. Alcohol 13-OH is identical with that prepared by lithium aluminum hydride reduction of the minor ester 15 from the direct methylation and is readily distinguishable from the other stereoisomer, 12-OH, prepared from the major ester 14. Since the direct methylation gives only modest yields of esters 14 and 15, and moreover the syn-carbomethoxy compound 15 is the minor component, the alternative synthesis uia lactone 17 affords a practical route to 13-OH as well as a firm basis for stereochemical assignments to the entire series. Synthesis and Characterization of the Products Expected from Ring Expansions of 12 and 13. By analogy to the reactions of the unmethylated compounds 2 and 3,2aring-expanded products from 12 and 13 are expected to fall into two categories. One of the sets of products should be related to the tricyclic cation 21 (L'), which would result from interaction of the double bond with the cationic site in the second rearrangement step. The other set should derive from the allylic cation 22 (G'). In addition, there might be either or both of the stereoisomeric products formally derivable from the once-rearranged 2-methylbicyclo[2.2.2]oct-5-en-2-ylcation 23 (see Scheme 11). These products 24 and 25 from 23 are readily obtained as a vpc-separable mixture by the action of methyl Grignard reagent on bicyclo[2.2.2]oct-5-en-2-one.6 Their stereochemistry is assigned6in part on the basis of the difference in chemical shift of the methyl protons in the parent compounds and a series of derivatives; additional grounds for the assignments come from perman(4) S.Beckmann and H. Geiger, Chem. Ber., 94,48 (1961). ( 5 ) (a) W. D. Closson, P. Wriede, and S. Bank, J . A m . Chem. Soc., 88, 1581 (1966); (b) H. L. Goering and R. W. Thies, ibid., 90, 2967 ( 1968). (6) N. Kundu, Ph.D. Thesis, University of Wisconsin, 1966.
Berson, Donald, Libbey J 7-Norbornylcarbinyl and 7-Norbornenylcarbinyl Derivatives
5582 Scheme I
'& +cxH + 17
18
19
19a
p0.t-R~
CH,OH
20-OH
C
Li/NH,
13-OH
x
C
13-OTs
X
T
s
20.0Ts
t 15
14
12-OH
Scheme I1
12
21 (L'i
or
21 (L'j
11
13 21 (L')
ganate oxidations in which the endo-hydroxy isomer 24-OH gives a lactonic acid but the exo-hydroxy compound 25-OH gives a dibasic hydroxy acid.'
OH 240H
26-OH
refrigeration and filtration of a concentrated hexanesolution of the mixture, which removes most of the 4-methyl isomer, 28-OH. Conversion of the acid to the acid
CH, 25-OH
27-OH
The epimeric I-methyltricyclo[3.2.1 .02~7]octan-6-ols, 26-OH ( e x o ) and 27-OH (endo), which derive from cation 21 (L') are obtained from the corresponding ketone, 32, which in turn is synthesized by the sequence shown. 31 30 Diels-Alder addition of isoprene to methyl acrylate gives a mixture of methyl esters of 4- and 3-methylcyclohex-3-ene-I-carboxylic acids (28-OCH3 and 29-OCH3). Saponification to the free acids and recrystallization afCHI fords the major component, the 4-methyl isomer, 32 28-OH, in pure form.8 The desired 3-methyl isomer, 29-OH, can be brought to about 88 purity by repeated chloride and addition of the latter to an ethereal solution of diazomethane give the diazo ketone 31 along with the (7) D. G . Morris, unpublished work. isomeric 4-methyl diazo ketone and variable amounts (8) H. E. Hennis, J . Org. Chem., 28,2570 (1963). Journal of the American Chemical Society / 91:20 / September 24, 1969
5583
of chloro ketone 30. Addition of this mixture in high dilutioneto powderedcopper suspended in boiling hexane produces 1-methyltricyclo[3.2. 1.02~7]octan-6-one (32) admixed with unreacted chloro ketone 30 and 2-methyltricyclo[3.2.1 .02y7]octan-6-one(33) which is present because of the approximately 12 % of 4-methylcyclohex-3ene-1-carboxylic acid (28-OH) in the starting material. The product is purified partially by vpc to give a 96:4 mixture of 32 and 33, which upon reduction with lithium aluminum hydride gives a mixture of three alcohols easily separable by vpc.
cx-x -
-
r
12
&OH
&OH
iH,
dH, 33
dH, 35
34
The major component of the reduction mixture ( 8 4 x ) is 1-methyltricyclo[3.2.1 .02~7]octan-endo-6-01 (27-OH); this stereospecificity is reminiscent of that observed in the sodium borohydride reduction of the parent ketone, tricyclo[3.2.1 .02s7]octan-6-one.lo Stereochemical equilibration (aluminum isopropoxide in isopropyl alcohol) gives a mixture of 80% exo-alcohol 26-OH and 20% endo 27-OH, a result that is again in accord with the observations in the parent series. lo The remaining two alcohols from the borohydride reduction of ketone 32 are l-methyltricyclo[3.2.1.02~7]octan-exo-6-ol (26-OHY 10 %) and 2-methylthe tricyclo[3.2.1 .02*7]octan-endo-6-01 (34-OH, 5 latter material arising from the contaminant ketone, 33. A small amount of the 2-methyl-exo-6-01 (35-OH) undoubtedly is formed but escapes detection. The products related to cation 22 (G') are allylic alcohols, which fall into two pairs of epimers: l-methylbicyclo[3.2.l]oct-2-en-exo-and -endo-4-ols (36-OH and 37-OH), and 1-methylbicyclo[3.2.Iloct-3-en-exoand -endo-2-ols (38-OH and 39-OH). The corresponding acetates are conveniently prepared merely by heating a mixture of the two unsaturated tertiary acetates 24OAc and 25-OAc at 120" in acetic acid. The two exo allylic acetates 36-OAc and 38-OAcYaccompanied by the endo isomers 37-OAc and 39-OAcYare formed in
x),
I
OAc 24OAc
36-OAc
C,H,
-
x-cx 1-
A
! I
A
Control experiments show that this mixture of allylic acetates is formed under thermodynamically controlled conditions from ring expansion of either of the 7-methylnorborn-2-enyl-7-carbinyl systems, 12 or 13. A 7-ethylnorborn-2-en-7-yl cation 40 would result if vicinal methyl shift occurred before ring expansion in either 12 or 13. Of course, the same cation need not
I
13
40
necessarily be formed from both precursors, but in any case, a 7-ethylnorborn-2-en-7-01 product might be expected. One of the isomers of this structure, probably syn-7-ethylnorborn-2-en-7-anti-01 (41) results from the action of ethyl Grignard reagent on norborn-2-en-7-one (42). The stereochemistry is not critical for our purposes and is assigned here merely by analogy to the reaction of 42 and methyl Grignard reagent. l 2 0
41-OH
42
Acetolytic ring expansions are found to be unsuitable for the study of memory effects in the 7-methylnorborn2-en-7-carbinyl system because of the instability of several of the important products to the reaction conditions (see below). There are several other aspects of the chemistry of the derived carbonium ions under acetolysis conditions that nevertheless are relevant and are described here. Nitrosative deamination conditions do permit an examination of the memory effect, and the results are given in a later section of this paper. The sodium acetate buffered acetolyses of syn-7-methylnorborn-2-enyl-anti-7-carbinyl p-bromobenzenesulfonate (12-OBs) and the anti-7-methyl-syn-7-carbinyl isomer (13-OBs) at 120" for 0.5 half-life give product
1 f
CH3 25-OAc
37-OAc
nearly quantitative yield. The structures are assigned by comparison of the spectroscopic properties with those of independently synthesized l 1 authentic samples. (9) Cf.W. von EI Doering, E. T. Fossel, and R. L. Kaye, Tetrahedron, 21, 25 (1965). (10) N. A. LeBel and J. E. Huber, J . Am. Chem. SOC.,85, 3193 11963). --,(1 I ) J. M McKenna, Ph.D. Thesis, to be submitted to the University of Wisconsin, 1969.
38-OAc
39-OAc
mixtures that are not kinetically controlled. Separate tests show that even after such relatively short exposures the two tertiary bicyclo[2.2.2]octeny1 acetates (24-OAc . and 25-OAc), as well as 1-methyltricyclo[3.2.1 .O2t7]octan-exo-6-yl acetate (26-OAc), all are converted entirely to the mixture Of allylic acetates 36-OAcY37-OAc,
\--
(12) R. K. Bly and R. S. Bly,J. Org. Chem., 28,3165 (1963).
Berson, Donald, Libbey 1 7-Norbornykarbinyl and 7-NorbornenyIcarbinyI Derivatives
5584 Table I. Percentage Composition of Products from the Acetolysis“ of 12-OBs and 13-OBs Productsb+ 41-OAc Ac
B CC 12-OAc Dc Ec 38-OAcd 37-OAc 36-OAc 13-OAc
26 0 0 0 33 0 0 9.5 2.6 29 0
38-OAc, and 39-OAc. The products of acetolysis from the two substrates 12-OBs and 13-OBs are given in Table I. The product distribution from the anti-7-carbinyl substrate 12-OBs is unremarkable. It consists of some unrearranged primary acetate 12-OAc, some product of methyl shift, 41-OAc, and some of a mixture of ring-expanded allylic acetates 36-OAc, 37-OAc, 38-OAc, and 39OAc. Acetolysis of thesyn-7-carbinylsubstrate,however, gives a sharply contrasting product mixture, which contains, in addition to a little methyl-shifted acetate 41OAc and substantial amounts of unrearranged (13-OAc) and ring-expanded (36-OAc, 37-OAc, 38-OAc, and 39-OAc) acetates, a set of five new compounds A, B, C, D, and E, totaling almost half of the products. These materials show no olefinic proton absorption in the nmr and presumably are tricyclic. A reasonable working hypothesis would attribute their formation to interaction between the double bond and the developing positive charge on the syn-carbinyl side chain, giving the tricyclic cation 43 or perhaps its nonclassical variant 44.
43
3. RsCI, I’y
OH 47
18
0.8 4.3 6.7 7.7 0 15 12 7.7 1.5 22 224
a The sodium acetate concentration in both runs was 0.0248 M. A separate run with 13-OBs in which the sodium acetate concentration was doubled produced an increase in the amount of primary product 13-OAc to 2 4 z . The rest of the relative distribution was unchanged. * Products present after 0.5 half-life. These are not kinetically controlled. c Product from attack on the double bond by the carbinyl carbon (see text). d A small amount of the endoallylic isomer 39-OAc undoubtedly is present but is not separated from 38-OAc under the analytical conditions. 3-Methylnortricyclyl-3-carbinyl acetate is not detectable among the products.
13-OBs
2. KOH
Starting material 12-OBs 13-OBs
48
49
&jOH
+
& I
46-OH
OH 45-OH
Lithium aluminum hydride reduction of ketone 49 gives two alcohols in a ratio of 5.6: 1. The major alcohol probably has the endo configuration 45-OH, but a firm basis for this assignment is not now available. Regardless of configuration, the method of synthesis and the spectroscopic data leave no doubt of the gross structure of these two alcohols. The acetate of the major alcohol from the tricyclic ketone 49 now proves to be identical in vpc retention time and ir and nmr spectra with the acetate D, the major “unknown” product from acetolysis of the syn-carbinyl p-bromobenzenesulfonate 13-OBs (Table I). The epimeric acetate from tricyclic ketone 49 has a vpc retention time identical with that of acetate B or C (Table I), which are not well resolved. Moreover, the p-toluenesulfonate of the major alcohol from ketone 49 (probably 45-OTs) gives upon acetolysis the same five acetates, A, B, C, D, and E, as are observed in the acetolysis of syn-carbinyl substrate 13-OBs (Table I). Aside from an excess of the acetate B (probably the exo compound, 46-OAc, epimeric with the starting 45-OTs), the relative proportions of the acetates from 45-OTs are virtually the same as those of this group from 13-OBs. Acetates A-E thus are clearly derived from tricyclic cation 43 (or 44) and its rearrangement products. These acetates amount to a total of 45 % of the product mixture from anti-7-methyl-syn-7-carbinyl substrate 13-OBs (Table I). This efficient cyclization involving the syn-carbinyl side chain and the double bond in the 7-methyl system 13-OBs is to be contrasted with the behavior of the 7-unsubstituted analog 2-OBs, which gives no detectable cyclization p r o d ~ c t s . ~ ” It J ~is conceivable that the 7-methyl group
44
Nucleophilic capture of these cations should lead to 1-methyltricyclo[3.3 .0.03~*]octan-4-endo-(and/or -em-) yl acetate, 45-OAc and/or 46-OAc. This speculation is confirmed by an independent synthesis of acetates 45 and 46, which starts with the previously described diol 18. By careful treatment with acetic anhydride-pyridine, 18 is converted to a mixture from which the primary monoacetate 47 can be separated by column chromatoggraphy in 50% yield, Successive steps of oxidation, saponification, and p-bromobenzenesulfonylation give the arenesulfonoxy ketone 48, which is converted by sodium hydride to the tricyclic ketone 49 in 85% yield.
13-OBs
2-OBS
of 13-OBs causes subtle distortions of molecular geometry that might produce this difference. Compressions of the C-7, C-I, C-2 and C-7, ‘2-4, C-3 angles, which would result from nonbonded repulsions between the 7-methyl group and the exo hydrogens at C-5 and C-6, would bring C-8 closer to C-2 and C-3 and thereby nar(13) R.K. Bly and R.S . Bly, J . O r g . Chem., 31, 1577 (1966).
Journal of the American Chemical Society / 91:20 / September 24, 1969
5585 Table II. Titrimetric Rate Coefficients for Acetolyses of pBromobenzenesulfonates at 120.4’ Substrated
k
x
105. S K - ~
1.76. (1.50)” 2OBs
1.37a (1.08)c 3.OBs CH,OEb
LE7
2.8ga(2.64)”
I-OBs
25” 13-OBs
9.0
cxBs 4.45b
12.OBs
28.06 50.OBs
Value corInterpolated from data of ref 13. * This work. rected for bimolecular component. d Initial concentration about 0.02M; sodium acetate initial concentration about 0.025-0.03 M.
row the energy gap between the ground state and the transition state for cyclization of C-8 and C-2 or (2-3. If this interaction occurred in the ionization step, ‘it would anchimerically assist the solvolysis rate. Kinetic studies of the solvolyses of 13-OBs and related substances provide a test of this. They also bear on the question whether the first step in the ring expansion may be anchimerically assisted and hence on whether the memory-preserving cationic intermediate so generated may be a nonclassical ion. Acetolysis Rates. Table I1 shows the effect of a syn-double bond and of a P-methyl group on the rate of acetolysis. The first three entries of the table give values for the 7-unsubstituted compounds 2-OBs, 3-OBs, and 1-OBs. They are taken from the data of Bly and Bly13 and serve as reference points for the 7-methyl series, 13-OBs, 12-OBs, and 50-OBs. The rate processes of interest here are the unimolecular components of the total displacement reaction. For some of these primary substrates, however, there is a strong presumption of a substantial bimolecular contribution, and in one case, 1-OBs, there is definite evidence of it.2b Accordingly the rate coefficients should be adjusted to some fraction of the observed values. Such adjustments are small and can be made to a good approximation for part of the bimolecular component, the direct displacement by the sodium acetate buffer. l 4 The corrected values are listed in parentheses in Table 11. These values, of course, still may contain a bimolecular component of unknown size because of solvent (14) D. S. Donald, Ph.D. Thesis, University of Wisconsin, 1969, and references cited therein.
Berson. Donald, Libbey
participation. This probably would not have a large effect on the search for r participation, since the contribution might be expected to remain roughly constant in comparisons between syn and anti or syn and saturated substrates. In evaluations of the P-methyl substituent effect, however, there would be a significantly larger bimolecular component in solvolyses of the isobutyllike 7-unsubstituted substrates than in those of the neopentyllike 7-methyl series. Therefore, the rate ratios calculated on the basis of the partially corrected values are minimum estimates of the magnitude of the P-methyl effect on the unimolecular rate. Bly and Bly13 have already concluded that r-bond participation is insignificant in the norborn-2-enyl-syn7-carbinyl system, 2-OBs, since the rate is not enhanced (Table 11) and no products of ring closure are observed. In the 7-methyl series reported here (Table II), it would be hard to make a case for a significant rate enhancement of the solvolysis of the syn-carbinyl compound 13-OBs. Although the rate is about twice as fast as that of the anti isomer, the increase is too small to require a special explanation. The rate for the saturated compound 50-OBs is about three times as fast as that of the syn isomer, an increase comparable in sense and size with that in the 7-unsubstituted series (Table 11). Thus, despite the ring closure of 45 of the product in the solvolysis of the 7-methyl-syn-7-carbinyl substrate, 13-OBs, no significant rate enhancement occurs. Apparently, the interaction of the K bond of 13-OBs with the carbinyl cationic center occurs late on the path to the ratedetermining transition state, or possibly even after it. Substitution of methyl for hydrogen at C-7 produces a modest rate enhancement in each case. The corrected ratios of acetolysis rate coefficients for the syn-carbinyl (13-OBs/2-OBs), for the anti-carbinyl (12-OBs/3-OBs), and for the saturated (50-OBs/l-OBs) pairs are 6.3, 3.3, and 10.6, respectively. Qualitatively, a rate enhancement by @methyl substitution is consistent with a hypothetically concerted ionization ring expansion (e.g., 51 -t 52), which would transfer some of the positive charge to the /3 position in the transition state of the rate-determining heterolysis. It is difficult, however,
d
51
52
53
to decide whether the magnitude of the effect is appropriate, because the interpretation of solvolyses of simple model compounds of the neopentyl type is still controversial.151l6 Perhaps the closest monocyclic analog of the 7-norbornylcarbinyl structure 51 is the cyclopentylcarbinyl system. Table I11 gives a series of acetolysis rate comparisons from the literature; 15-18 the values in parentheses are approximate ratios obtained by comparison of two rates through a common reference or a reasonable model compound. (15) (a) W. G. Dauben, J. L. Chitwood, and K. V. Scherer, Jr., J . Am. Chem. Soc., 90, 1014 (1968). (16) W. G. Dauben and J. L. Chitwood, ibid., 90,6876 (1968). (17) P. D. Bartlett, W. D. Closson, and T.J. Cogdell, ibid., 87, 1308 (1965). (18) G. Le Ny,Compt. Rend., 250,368 (1960).
/ 7-Norbornylcarbinyl and 7-NorbornenylcarbinyI Derivatives
5586
Scheme I11
L’ product 4
~
12
55
Relative rate comparison G of Table I11 shows that @methyl substitution enhances the rate of acetolysis of a cyclopentylcarbinyl substrate by a factor of about 11. Previous workers 17- l9 have suggested that relief of strain by carbon participation may provide a driving force in the solvolysis of this system. On this basis, one might expect that in 7-norbornylcarbinyl solvolyses (51 + 52), relief of strain might be even more pronounced; if present, however, this effect is overcome by some other factor, since the 7-norbornylcarbinyl solvolysis is slower, not faster, than the cyclopentylcarbinyl one (ratio H, Table 111). The 10.6-fold acetolysis rate enhancement by 7-methyl substitution in the 7-norbornylcarbinyl system is almost exactly the same as that in the cyclopentylcarbinyl case (Table 111, G). This may well be fortuitous, but it seems reasonable to conclude that the importance, if any, of carbon participation in both the monocyclic and bicyclic systems is comparable. The modest 6-methyl effects and rather slow absolute rates observed in the present ring expansions are to be contrasted with the results of solvolyses of exo-norbornyl systems, which are widely (but not universally) believed to involve strong anchimeric assistance by carbon participation in a transition state leading to a nonclassical cationic intermediate. The exo norbornyl rates are fast,20 and a 6-methyl substituent increases the acetolysis rate by a factor of 68 at 25°.21 By themselves, the rather feeble rate effects in the 7-norbornylcarbinyl systems could hardly form a strong basis for the postulate of a nonclassical transition state (52) or intermediate (53) in the ring expansions. Yet such ions provide one of the few consistently useful working hypotheses for the interpretation of the memory effects. 2 2 Thus, if the memory-preserving ions encountered2a$bin 7-norbornylcarbinyl or norborn-2-enyl-7-carbinyl ring expansions are nonclassical, the kinetic tests used here fail to detect them with certainty. The memory effect, which uses a symmetry property as the means of detection, is a much more sensitive probe. (19) J. E. Nordlander, S. P. Jindal, P. von R. Schleyer, R. C. Fort, Jr., J. J. Harper, and R. D. Nicholas, J . A m . Chem. Soc., 88,4475 (1966). (20) J. A. Berson in “Molecular Rearrangements,” Vol. 1, Part 3, P. de Mayo, Ed., Interscience Publishers, New York, N. Y., 1963. (21) P. von R. Schleyer, as cited in ref 20, p 182. (22) J. A. Berson, Angew. Chem. Intern. Ed. En& 7,779 (1968).
Journal of the American Chemical Society
21 (L‘)
21
(L‘)
Tests for Crossover of Cation G’ + L’ and Vice Versa. Scheme I11 presents a basis for analysis of memory effects in the ring expansions of 7-methylnorborn-2-enyl-7-carbinyl derivatives analogous to that Table 111. Ratios of Acetolysis Rates
Compounds
-Relative rateCode letter Value 3.5
Temp, “C
80
2.5
17
18
75
19
75
14
(35)
75
a
(1)
75
b
(11)
75
c
13
115
114
0.33
E E CD.
Ref
* F is assumed to be unity.
13, 17, 18
G E E/BF.
usedZafor the parent 7-unsubstituted compounds. In order to preserve any of whatever stereochemical specificity is transmitted by the once-rearranged “twisted” cations 54 and 55, it is necessary that the twice-rearand 21 (L’) be trapped as products ranged ions 22 (G’)
1 91:20 1 September 24, 1969
5581
at rates that are at least competitive with the rates at which they interconvert with each other. An examination of the behavior of independently generated cations G’ and L’ provides some measure of how serious a problem the interconversion rate may be. Acetolysis of l-methylbicyclo[2.2.2]oct-5-en-endo-3-yl p-toluenesulfonate (56-OTs) at 40” gives a mixture of allylic acetates consisting mainly of the e m compounds 36-OAc and 38-OAc, with traces of the endo epimers 37-OAc and 39-0Ac.l’ Products (e.g., tricyclic com-
some such species as tertiary bicyclic cation 23. The presence of bicyclic acetates 25-OAc (2 1 %) and 24-OAc (5-6%) in the product mixture is consistent with this scheme. These background studies indicate that whatever memory effect inheres in the double rearrangement of syn-carbinyl compound 13 to cation G’ (Scheme 11) will persist in the product pattern, but that in the rearrangement of anti-carbinyl compound 12 to cation L’ it inevitably will be largely or wholly lost. 2 3 Memory Effects in the Deaminative Ring Expansions of the 7-Methylnorborn-2-enyl-7-carbinylamines. Nitrosative deaminations of the syn-carbinylamine 13NH2 and its anti isomer 12-NH2 in glacial acetic acid at room temperature give the mixtures of products shown in Table IV. The differences in product distributions, although small, appear to be outside of experimental error. In particular, the G’/L’ ratio from syn-amine 2, and that from anti-amine 12-NH2is 13-NH2 is 18 10 f 2. It would seem that some memory is preserved, even in this system, where quasi-symmetrization to tertiary cation 23 (Scheme 11) might be expected to compete more favorably with cr or 7~ entrapment of “twisted” cations 54 or 55 than in the unsubstituted case. Because of the extensive crossover suffered by cation system L’, the L’/G’ ratio (or G’/L’ ratio) from anti- (or syn-) amine is not a meaningful measure of the memory effect, and experimental difficulties preclude an adjustment of the observed values to correct for crossover. Moreover, as is always the case in quasi-symmetrical rather than truly symmetrical systems,2a the product ratio is not directly translatable into a ratio of
*
pound 26-OAc) from the L’ cation 21, are present in no more than minor quantities. Crossover from the G ’ to the L’ cation series thus is slow at 40” in acetic acid, conditions similar to those used in the deaminations to be described. ,-
A
21 (L‘)
27-0T~
23
25-OAc
1
24-OAc
22 (c‘)
To test for crossover in the reverse direction (L’
27.0Ac
26-OAC
36.0Ac +
G’),we generate L’ cations from 1-methyltricyclo-
38-OAc
rates of u entrapment us. quasi-symmetrization because the “natural” partition ratio of the quasi-symmetric ion (e.g., in Scheme 111, the relative rates of 23 + G’and 23 --t L’) is unknown. Nevertheless, it is clear that mem-
[3.2.1.02~7]oct-endo-6-ol (27-OH). The p-toluenesulfonate 27-OTs is very unstable, but it is apparently formed when a cold Dvridine solution of 27-OH and (23) It is of incidental interest to inspect the products from the tertiary p-toluenesulfonyl chldr‘de is to stand‘ It is bicyclic cation system 23 generated in another way. These studies are acetolyzed by keeping in acetic acid* The acetate fratfragmentary, and results are available only for the deamination of the tion of the resulting product mixture contains not only two amines 24-NHz and 25-NHz. The endo-amino compound 24NHz gives 33 % bicyclic exo-acetoxy compound 25-OAc, 4 % endo epimer ~ and 2 7 - 0 ~ ~ 24-OAc, the expected I,’ products 2 6 - 0 ~(7.3 14% tricyclic L’ product 26-OAc, and 3 1 and IS%, respec(
+
Journal of the American Chemical Society
1 91:20 September 24, 1969
5589 and 20% 20-OTs, prepared as described above, in 40 ml of dry tetrahydrofuran and 13.3 ml of absolute methanol was placed in the dropping funnel and added dropwise to the stirred solution over a period of 1.5 hr. Stirring was continued for ca. 10 hr with Dry Ice cooling and without cooling for 8 hr while the ammonia was allowed to escape. The ether was replenished occasionally during this time. The addition of 34 ml of methanol brought about the discharge of the residual blue and bronze colors within 0.5 hr. About 150 ml of diethyl ether and 150 ml of water were added, the layers were separated, and the aqueous layer was extracted three times with a total of 150 ml of diethyl ether. The combined extracts were washed twice with 25-ml portions of 10% sodium hydroxide, once with saturated sodium chloride solution, and dried (CaSO,). Careful removal of the ether through a Vigreux column left 1.905 g of oil which solidified upon standing in the cold. Sublimation at 12-15 torr up t o 80" using ice-water cooling gave 1.537 g (65%) of white, waxy material with a strong camphorlike odor. Vpc analysis on column B (110", 50 psi) showed the presence of two compounds in a ratio of ca. 4 :1. Compound 13-OH was obtained pure by preparative glpc on column C at 138" and 60 psi under which conditions it had a retention time of 50 min as compared to ca. 65 min for the minor component, tricyclo[2.2.1.02~~]heptyl-3-methyl-3-carbinol (20-OH). The pressure was reduced to 18 psi during collection. The collection efficiency was 79%. After sublimation t o remove column bleed the title compound melted 109.5-110.6"; ir (KBr) 3300 cm-l, 3030, 2915,2849, 1015, 870, 847, 800, 714, 699; nmr (CCI,) 6 5.88 (t, 2 H, J = 1.8 Hz, olefinic protons), 3.44 (s, 2 H, 3CCHzO), 2.99 (s, 1 H, -OH), 2.35 (broad, 2 H , C-1 and C-4 bridgehead protons), 1.80 (m, 2 H, C-5 and C-6 exo protons), 0.93 (s, 3 H , C-7 methyl protons), 1.10.7 (m, 2 H , C-5 and C-6 endo protons). Anal. Calcd for C S H I 4 0 : C, 78.21; H , 10.21. Found: C, 78.67; H, 10.05. The p-bromobenzenesulfonate 13-OBs was prepared by standard procedure (C) in 90% yield. Recrystallization from methanol gave needles: mp 80.0-81.5'; ir (KBr) 1351, 1189, 1176 cm-l; nmr (CDCI,) 6 7.73 (s, 4 H, aromatic protons), 5.82 (t, 2 H, J = 1.8 Hz, olefinic protons), 4.08 (s, 2 H , 3CCH20-), 2.5-2.28 (broad, 2 H, C-1 and C-4 bridgehead protons), 2.1-1.2 (complex, 2 H, exo C-5 and C-6 protons), 1.2-0.7 (complex, 2 H , endo C-5 and C-6 protons), 0.94 (s, 3 H, C-7 methyl protons). Anal. Calcd for C15H17BrS03: C, 50.40; H, 4.80; Br, 22.39; S,8.97. Found: C, 50.45; H, 4.81; Br, 22.31; S,9.07. The 20% component of the mixture is tricyclo[2.2.1.0z~6]heptyl-3methyl-3-carbinol (20-OH) as indicated by its spectral properties, elemental analysis, and mode of synthesis. A sample was repassed as above and sublimed twice: mp 107-110"; ir (thin film) 3226 2941, 2874, 1460, 1025, 800 cm-l; nmr (CCl,) 6 3.42 (central lines of AB pattern, 2 H, J = 8 Hz, 3 CCHzOH), complex pattern from 2.0 to 0.6 (broad peaks at 1.72, 1.58, 1.42, 1.22, and a fairly sharp peak at 1.04,8 H), 0.93 (s, 3 H , methyl protons). Anal. Calcd for CsH140: C, 78.21; H, 10.21. Found: C, 78.07; H, 10.33. 2-Norbornenyl-anti-7-methyl-syn-7-carbinyl acetate (13-OAc) was obtained from the corresponding alcohol with acetic anhydridepyridine (procedure B-1). The crude product, obtained in 93.3% yield, gave only one peak on column B (1 lo", 50 psi). Bulb-to-bulb distillation gave the material as a clear, water-white oil: ir (neat) 1739, 1235, 1026, 719 cm-l; nmr (CC14) 6 5.93 (t, 2 H, J = 1.9 Hz, olefinic protons), 3.99 (s, 2 H, -CCH20), 2.40 (broad, 2 H, C-1 and C-4 bridgehead protons), 1.92 (s, 3 H, acetoxy methyl), 2.1-1.6 (m, 2 H, exo C-5 and C-6 protons), 1.2-0.80 (m, 2 H, endo C-5 and C-6 protons), 0.92 (s, 3 H, C-7 methyl). Anal. Calcd for C11HlS02: C, 73.30; H, 8.95. Found: C, 73.08; H, 8.85. 3-Methyltricyclo[2.2.1.0z~6]heptylcarbinyl Acetate (20-OAc). This material was prepared by procedure B-1 from the corresponding alcohol. Bulb-to-bulb distillation gave a water-white liquid : ir (neat) 3067, 2967, 2882, 1739, 1464, 1387, 1377, 1235, 1032,982, 907, 829, 800 cm-l; nmr (CCI,) 6 3.83 (AB pattern, 2 H ; JAB= 11 Hz, AVAB= 6.93 Hz, 3 CCHzO-), 1.97 (s, 3 H, CHaCOO), 1.78 (broad, 1 H), 1.60 (broadened singlet, 2 H), 1.24 (broadened singlet, 1 H), 1.18-0.70 (complex pattern with peaks at 1.13, 1.06,0.90, 0.82,0.74, 4 H ) , 0 . 9 4 ( ~ 3, H , 3CCH3). 7-Methyl-7-norbornylcarbinol(4-OH) was prepared by hydrogenation at atmospheric pressure of 0.2980 g (2.16 mmol) of 13-OH in methanol using 10% palladium on charcoal. After filtration to remove catalyst and careful removal of solvent through a Vigreux column, the crude alcohol was sublimed under aspirator vacuum, up to loo", using ice-water cooling, giving 0.2730 g (90.5z) of
material: mp 152.7-153.2"; ir (KBr) 3333, 1471, 1029, 998 cm-I; nmr (CCl,) 6 3.50 (s, 2 H, 3 CCHzO), 2.0-0.8 (complex, 10 H), 1.04 (s, 3 H , C-7 methyl). Anal. Calcd for CsH160: C, 77.10; H, 11.50. Found: C, 76.89; H, 11.23. The p-bromobenzenesulfonate (4-OBs) was prepared in 93.5 yield by standard procedure (C). Recrystallization from methanol gave white plates: mp 72.0-73.0'; ir (KBr) 1351, 1178 cm-l; nmr (CDCI,) 6 7.64 (broad s, 4 H, aromatic protons), 3.99 (s, 2 H, =CCH20), 2.0-0.8 (complex, 10 H), 0.99 (s, 3 H, C-7 methyl). Anal. Calcd for Cl6HlBBrSO~:C, 50.14; H, 5.33; Br, 22.24; S,8.93. Found: C, 50.12; H, 5.35; Br,22.26; S,8.90. 2-Norbornene-anti-7-methyl-syn-7-carbinylphthalimide. In a 25-ml one-necked flask equipped with a condenser and drying tube and closed to the atmosphere using a mercury bubbler were placed 0.3319 g (0.930 mmol) of 13-OBs, 0.2745 g (1.86 mmol) of phthalimide (recrystallized from ethanol and sublimed), 0.1280 g (0.930 mmol) of potassium carbonate, and 5.7 ml of dimethylformamide (shaken with potassium hydroxide and distilled from calcium oxide). The initially yellow solution containing solid potassium carbonate was placed in an oil bath at 160" whereupon the solid dissolved within 20 min with the evolution of gas. In ca. 45 min a solid began to form and after 15 hr the orange solution was cooled to room temperature and 15 ml of cold water was added and the stirring continued for 15 min. The slightly yellow solid which formed was filtered off and washed well with water, sucked dry, and dissolved in 20 ml of diethyl ether. The ether solution was washed with 5 ml of 2 % sodium hydroxide solution which gave no precipitate upon acidification. The ether solution was washed with saturated sodium chloride and dried over calcium sulfate. The ether was removed under a stream of nitrogen leaving 0.1760 g (71 %) of slightly yellow powder. Recrystallization from methanol gave white crystals: mp 122.0-123.0"; ir (KBr) 1757, 1701, 1385, 1058, 911, 733, 720, 714 cm-'; nmr (CCl,) 6 7.72 (two-line pattern with weaker lines, 4 H , J = 2 Hz, aromatic protons), 6.05 (A2X2 pattern appearing as a triplet, 2 H, J = 1.9 Hz, olefinic protons), 3.75 (s, 2 H, 3 CCH2N
