Methylenecyclohexane, and

The effect of introducing -hybridized atoms into open-chain molecules was discussed earlier, and it was noted that torsional barriers in 1-alkenes and aldehydes are somewhat smaller than in alkanes. Similar effects are noted when sp centers are incorporated into six-membered rings. Whereas the fiee-energy barrier for ring inversion in cyclohexane is 10.3 kcal/mol, it is reduced to 7.7 kcal/mol in methylenecyclohexane and to 4.9 kcal/mol in cyclohexanone. ... 

Figure 13.21 (a) The 1H NMR spectrum of cyclohexylmethanol, the product from hydroboration/oxidation of methylenecyclohexane, and (b) the 1H NMR spectrum of 1-methylcyclohexanol, the possible alternative reaction product. 

FIGURE 4.48 Substrates (3,3,6,6-tetradeuterocyclohexene, methylenecyclohexane, and/ -pinene) used to determine the mechanism of cytochrome P450-catalyzed allylic hydroxylation. 

The material obtained in this manner is of high purity before distillation it has the same refractive index as the distilled methylenecyclohexane, and no impurities could be detected by gas chromatographic analysis on two different columns. 

Devise a synthesis for each compound, starting with methylenecyclohexane and any other reagents you need,... 

The reaction is not regioselective for methylenecyclohexane and its 4-substituted derivatives (entries 1 and 2), slightly regioselective in the case of the 2-alkoxy-substituted alkene (entry 3), and completely regioselective for the enol lactone (entry 5). 

The configuration of the produced diol is influenced by the relative stabilities of the benzyl- or alkylcarbonium ions formed during the reaction. Similar reactions were investigated earlier. The rate and stereochemistry of the diborane reaction is altered by a small quantity of LiCl. Wide-ranging research has been performed with regard to the mechanism and stereochemistry of the diborane reduction in connection with cyclic and aliphatic a, 3-unsaturated and allylic epoxides, on diterpene models, " and by study of the reduction of epoxy-methylenecyclohexane and 2,3-epoxy-3-methylcyclohexanone. ... 

The purpose of preparing aliphatic amine oxides is usually their thermal decomposition to cis alkenes and N,N-dialkylhydroxylamines (Cope rearrangement) [156, 161, 1187]. Thus A, A -dimethylcyclohexylmethylamine is oxidized with 30% hydrogen peroxide in methanol to its oxide, whose decomposition at 90-100 °C at 10 mm of Hg and at 160 °C for 2 h furnishes 79-88% of methylenecyclohexane and 78-90% of A, A -dimethylhydroxyl-amine [161], Another example is the preparation of cw-cyclooctene from dimethylcyclooctylamine (equation 502) [1187]. 

Exocyclic double bonds generally also form the expected complexes. However methylenecyclohexane and 1 -methylcyclohexene are converted mainly into toluene. 

The fundamental principles of asymmetric synthesis employed throughout also apply to ene reactions. Chiral additives, chiral auxiliaries, and the preparation of chirons all lead to good enantioselectivity when applied to the ene reactions. Most chiral ene reactions seem to involve addition of a chiral catalyst or the use of a chiral auxiliary. Oppolzer et al. utilized a chiral auxiliary in 713 to prepare 714 (90 % de) in a synthesis of (+)-a-allokainic acid.515 Yamamoto used the chiral aluminum catalyst 715 for the intermolecular ene reaction of 1,6-dichlorobenzaldehyde and 2-phenylthio-l-propene to give 716 in 96% yield (65 % ee).5i6 These catalysts are similar to those used in Section 11.9.B. A similar titanium catalyst (717) was used to couple methylenecyclohexane and methyl glyoxalate, giving 89% of 718 (98 % ee). The titanium catalyst... 

In the presence of methanol as solvent and 1,4-dicyanobenzene as acceptor, photoinduced electron transfer from 1,4-bis(methylene)cyclohexane gives 4-(methoxymethyl)-1 -methylenecyclohexane and 4-(4-cyanophenyl)-4-(methoxy-methyl)-l-methylenecyclohexane which arise by nucleophilic attack of the solvent on the radical cations, followed either by reduction and protonation, or by combination with the radical anion of the electron acceptor.These observations are in accordance with the proposed mechanism of the nucleophile-olefin combination, aromatic substitution (photo-NOCAS) reaction. The same group has also investigated the use of cyanide ion as nucleophile and report that irradiation of a mixture of 1,4-dicyanobenzene in the presence of biphenyl as donor, KCN, and 18-crown-6 gives a mixture of (79) and (80). These workers have also extended the scope of NOCAS to fluoride ion. In particular, use of 2,3-dimethylbut-2-ene and 2-methylbut-2-ene gives 4-cyanophenyl substituted... 

Unhindered methylenecyclohexanes and related compounds show a moderate preference for axial epoxidation. In the epox-... 

Preparation of Tertiary Amines from Alkenes and Secondary Amines. A useful preparation of tertiary amines from alkenes can be achieved when a secondary ozonide is treated with a secondary amine (eq 50) 7 The reaction is quite versatile and provides tertiary amines when the reaction is carried out at reflux after addition of the amine. When the reaction medium was kept at room temperature, isolation of the enamine was observed, making this a clean, four-step, one-pot preparation of morpholino enatnines and tertiary amines for use in s)uithesis. Overall, the reaction performed best with morpholine some problems were encountered with methylenecyclohexane and piperidine, as it seems the enamine intermediate is difficult to form in such a hindered system. 

Again, using a basis scale of 1 mol of triphenylphosphine oxide target product produced this two-step sequence would result in the production of 0.096kg methylenecyclohexane and 0.278kg... 

The E-factor breakdown for this recycling reaction is as follows E-kernel = 0.57 E-excess = 0.046 E-auxiliaries = 7.74 and E-total = 8.35. If we link this recycling reaction with the scheme shown in Figure 11.6, which produces 0.096 kg methylenecyclohexane and 0.278 kg triphenylphosphine oxide, then we can calculate the total waste produced from the original two-step reaction and the recycling reaction. From the first two-step sequence, we produce 14.90-0.278 = 14.622 kg net waste. If we take the recovered 0.278 kg of triphenylphosphine oxide and subject it to the recycling reaction we will... 

Cyclohexenes and Cyclohexadienes. The stereochemistry of cycloadditions to methyl-enecyclohexanes has been a somewhat neglected area. Recently, the addition of dichloroketen and chlorosulphonyl isocyanate to methylenecyclohexane and 4-t-butylmethylenecyclohexane has been studied as models for a 2s + 2a allowed cycloaddition. The reaction is kinetically controlled and axial attack dominates, yielding the thermodynamically less stable isomer (as confirmed by a molecular mechanics calculation). There is complete regiospecificity due to the polar character of the transition state. 

Analyses of the C and n.m.r. spectra of 2-substituted methylenecyclo-hexanes (e.g. 2-methoxy-l-methylenecyclohexane) and 3-substituted cyclohexenes have demonstrated that a double bond stabilizes the axial or pseudoaxial con-former, respectively, when an electronegative substituent is present at the allylic position. Stabilization of the (pseudo)axial conformer by the double bond in both series is adequately explained in terms of double bond-no bond resonance [e.0. (641) <- (642)]. This effect is enhanced by a methoxy-group on the double bond, as in 2-methoxy-l-(methoxymethylene)cyclohexane. 

Scheme 932. The carbonyl ene reaction between methylenecyclohexane and methyl gly-oxalate (CH3O2CCHO) producing methyl 3-(l-cyclohexenyl)-2-hydroxypropanoate. Since addition can occur ou either the re or the si face of the carbonyl group, the product is racemic. The details of the Lewis add catalyst L have been omitted for clarity.

Scheme 9.33. The formation of a diasteromer of a 2-(l-methyl-l-phenyl)ethyl-4-methylcy-clohexyl 3-(l-cyclohexenyl)-2-hydroxypropanoate from tin(IV) chloride catalyzed ene reaction between methylenecyclohexane and the corresponding glyoxalate ester.

We have used inter- and intramolecular kinetic isotope effects to examine the mechanism of these Lewis acid catalyzed ene reactions. The Lewis acid catalyzed ene reaction has traditionally been though to proceed through either a concerted pericyclic mechanism or a stepwise reaction with a zwitterionic intermediate. We found that the intermolecular isotope effect in the Me2AlQ catalyzed ene reaction of formaldehyde is 1.3 with methylenecyclohexane and methylenecyclohex-ane-2,2,6,6- 4 and 1.4 with 2,3-dimethyl-2-butene and 2,3-dimethyl-2-butene- /i2. Since secondary iotope effects could be responsible for these results, these values are consistent with either a stepwise or concerted mechanism. Intramolecular isotope effects were determined to be 2.9 and 2.7 with 2 and 3, respectively. These substantial intramolecular isotope effects coupled with the small intermolecular isotope effects indicate that the reaction is stepwise with proton transfer following the rate determining step. In an intramolecular competition such as the ene reactions of formaldehyde with 2 and 3 an isotope effect will still be observed if the hydrogen transfer occurs... 

KHCOg, benzonitrile, methylenecyclohexane, and SO -HgOg added to methanol, stirred 18 hrs. with water-cooling below 30°, then warmed 4 hrs. at 45° - 1-oxa-spiro [5.2] octane. Y 73%.—The reagent is operative under mildly alkaline conditions. F. e. s. G.B. Payne, Tetrahedron 18, 763 (1962). 

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