The syntheses of a number of monosubstituted and 1,4-disubstituted cubanes are described, together with the measurement and analysis of their 100-MHz ' H N M R spectra. Typical coupling constants observed are 5.3 Hz (vicinal), 2.5 Hz (four bond), and -0.7 H z (five bond). A simple additivity rule is described whereby chemical shifts in CDCI, can be predicted to within d~0.02 ppm. Both chemical shifts and coupling constants are shown to var.y with substituent electronegativity. The derived correlations allow quick and effective identification of cubane derivatives from their ' H N M R spectra, and also aid in the interpretation of the more complex spectra of less symmetrical cage molecules. ResultsAnalysis of the Spectra. In all mono-or disubstituted cubanes, three geometries of proton spin-spin coupling are possible. Following Cole's designation2Q of cubane substitution patterns, we have termed these couplings oftho (along an edge of the cube), meta (across a face of the cube), and para (along a diagonal of the cube). The 1,4-disubstituted cubanes (I) form Ha Hn I J A B = JORTHO JAA,, JBBT = JMETA J'AB = JPARA an [AB13 spin system and the observed chemical shifts of HA and H B differ by < I ppm, depending upon the substituents X and Y. The monosubstituted cubanes (11) form a much more complex [AB]3C system, and in all the cases we have studied the B and C chemical shifts are very close (less than 0.05 ppm I1 J A W JR,. = JOKTHO J A A '~ JRH', JAC = JMWA J'AH = J i i A n Adifference). Thus their spectra are considerably more difficult to analyze than those of the 1,4-disubstituted cubanes.All spectra were analyzed using the LAOCN321 computer program and the results plotted on a Calcomp Plotter. Approximate values of coupling constants were estimated by first-order analysis of the nearly [AX13 spectra of the substituted 4-methylcubanes. These estimates were varied until the spectra computed from them were similar to the experimental spectra, and then the fit was optimized by iterative calculation. It is impossible to analyze the spectra exactly because of the enormous number of unresolved lines (less than 20 peaks and shoulders can be assigned in the average spectrum). Thus it is necessary to assign the calculated lines to fit under an ex-Edward, Farrell, Langford / Proton Magnetic Resonance Spectra of Cubane Derivatives 133.3' 376.7J " Chemical shifts in Hz at 100 MHz. All samples in CDC13 except as noted. Shifts calculated by eq 1. Same as HA. Hc shift. e OCH3 Unresolved singlet for A and B protons; IYIu d estimated from line width. The reverse assignment Solvent is D2O with TMT as external reference.shift. f CH3 shift. of A and B shifts is also possible. J CH20H shift, Ir R = (cubyl)C02CH3. C(CH3)3 shift. NHC02CH3 shift.Solvent is DZO/NaOD, with TMT as external reference.
. Can. J. Chem. 59,344 (1981). I-Methoxy-2-methyl-1,4-cyclohexadiene (3), 2-methoxy-I-methyl-1.3-cyclohexadiene (2), and 2-methoxy-1,5,5-trimethyl-1,3-cyclohexadiene (14) on heating with maleic anhydride give 1-methoxy-endo-7-methylbicyclo[2.2.2]oct-5-ene-syn-2,3-dicarboxylic acid anhydride (7) and its 6-methoxy-I-methyl(16a) and 6-methoxy-l,8,8-trimethyl(l6b) analogues, respectively. On hydrolysis 16a and 16b give the corresponding keto dicarboxylic acids, 18a and 18b, via keto anhydrides 17a and 17b. During the course of 13C nmr spectroscopic greatly favours the desired regiochemistry of the studies (1) and other work (2, 3) on bicyclo-Diels-Alder reaction in route C, alkyl substitution [2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octan-2-is rarely found to lead to regiospecific addition (6), ones we had occasion to synthesize several members and indeed it was observed (4) that the product of these series. We report this work here because we mixture from route A contained a small amount consider that it includes several features of intrinsic of 4-methylbicyclo[2.2.2]oct-5-en-2-one, the regiointerest.isomer of 1. We therefore thought it worthwhile to I-Methylbicyclo[2.~.2]oct-~-en-~-one and Related investigate an alternative route-for the preparationCompounds of the latter, and chose 1-methyl-2-methoxy-l,3-l-Methylbicyclo[2.2.2]oct-5-en-2-one (1) was hexadiene (2) as the dime component of a Dielsfirst obtained by routes A and B in Scheme 1 (4). In Alder reaction pathway to the desired producteach case 1 was formed as a component of a cornIt has been reported (7) that Birch reduction of plex mixture of products and it was isolated by 0-methylanisole gives a mixture of the 1,4-dienes 3 preparative gas-liquid c.,romatograp~y~ sub-and 4, which is converted on treatment with potassequently 1 was prepared in good yield by route c sium amide in liquid ammonia to a mixture of the in scheme 1 (5). ~l~h~~~h the uortho effect-1,3-dienes 2 and 5, in which the former is the major component; the structures of the conjugated dienes 'Present address: Raylo Chemicals, ~t d . ,8045 Argyll Road, were inferred from the Diels-Alder adducts that Edmonton, Alta., Canada T6C 4A9.they formed. However, although the Birch reduc-
The ketonic "C NMR signals of a series of 6-hydroxy-5-oxobieyclo[2.2.2]octt-7-ene-2-carboxylic acid lactones and of haplophytine and related N-substituted 3-piperidinones occur at exceptionally high field; the structural factors which are responsible have been elucidated by comparisons with related compounds.Carbonyl carbon signals in the 13C NMR spectra of organic compounds are usually readily identified since they normally occur in a region of the spectrum (6 170-225 ppm) in which few other types of carbon atoms give rise to signals.' They are of importance not only in revealing the presence of one or more carbonyl groups, but also in providing information concerning the functional environment of the carbonyl groups. Thus, simple saturated ketones normally give signals at 6 205-225 ppm and simple conjugated ketones at 6 190-200 ppm, while simple acids, esters, lactones, amides and lactams have signals at 6 170-190 ppm.l Gross deviations from these normal values are clearly of importance to organic chemists using 13C NMR spectroscopy as a tool for structural elucidation. We report our observations on such deviations in the cases of two classes of cyclic ketones (chemical shift values are given in ppm relative to internal TMS for solutions in CDCI,; negative values of differential shifts denote shielding effects).The first class comprises keto lactones of type 1,' whose ketonic carbon chemical shifts are listed in s~b s t i t u e n t ,~ but its magnitude is extraordinarily large. It can be compared with the effect of -5.3 pprn resulting on substitution of a 3-acetoxy group in 4a to give 4c. The effect is attributable largely to dipole-dipole interaction and its magnitude is considered to reflect, first, increased electrostatic interaction due to the rigidly held orientation of the lactone relative to the ketonic carbonyl group and, second, distortion of the geometry of the bicyclo[2.2.2]oct-5-en-2-one system.' A second factor is the P,y-ethylenic double bond. Introduction of such a double bond into cyclic ketones can lead to upfield shifts of their carbonyl carbon signals, which for bicyclo[2.2.2]octan-2-ones lie in the range of -4 to -6 ~p m .~,~ Comparison of la and 2 shows that here the ethylenic double bond leads to a shift of -5.6ppm. Such shifts are due in part to homoconjugation, but other effects play a role.5 The third factor is the presence at C-7 in l&li of a syn-or anti-carbomethoxy or -bromo substituent, which leads to a shift of -2.5 to -4ppm. Such y shielding effects on carbon by both gauche and anti electronegative p substituents have been observed previously.6 The only structural factors which lead to deshielding are the (Y -methyl substituents; however, their p deshielding
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