Ethers, methyl cyclohexenyl

Very few pericyclic reactions of carbene complexes have been studied that are not in the cycloaddition class. The two examples that are known involve ene reactions and Claisen rearrangements. Both of these reactions have been recently studied and thus future developments in this area are anticipated. Ene reactions have been observed in the the reactions of alkynyl carbene complexes and enol ethers, where a competition can exist with [2 + 2] cycloadditions. Ene products are the major components firom the reaction of silyl enol ethers and [2 + 2] cycloadducts are normally the exclusive products with alkyl enol ethers (Section 9.2.2.1). As indicated in equation (7), methyl cyclohexenyl ether gives the [2 -t- 2] adduct (84a) as the major product along with a minor amount of the ene product (83a). The t-butyldimethylsilyl enol ether of cyclohexanone gives the ene product 9 1 over the [2 + 2] cycloadduct. The reason for this effect of silicon is not known at this time but if the reaction is stepwise, this result is one that would be expected on the basis of the silicon-stabilizing effect on the P-oxonium ion. 

N-Methylaminopropyltrimethoxysilane Methyl t-butyl ether Methyl cocoate 2-(4-Methyl-3-cyclohexenyl)-2-propanol N-Methylcyclohexylamine Methylcyclohexyldichlorosilane Methylcyclohexyldimethoxysilane Methyidichlorosilane Methyl dichlorostearate Methyidiethanolamine... 

Fig. 4.7. Br0nsted relation for the hydrolysis of methyl cyclohexenyl ether. (Reproduced from reference 21 by permission of the American Chemical Society.)...

Br0nsted relation for hydrolysis of methyl cyclohexenyl ether... 

Another example is the hydrogenation of the homoallylic eompound 4-methyl-3-cyclohexenyl ethyl ether to a mixture of 4-methylcyclohexyl ethyl ether and methylcyclohexane. The extent of hydrogenolysis depends on both the isomerizing and the hydrogenolyzing tendencies of the catalysts. With unsupported metals in ethanol, the percent hydrogenolysis decreased in the order palladium (62.6%), rhodium (23 6%), platinum (7.1%), iridium (3.9%), ruthenium (3.0%) (S3). 

In general, hydrogenolysis of vinylic compounds is favored by platinum and hydrogenation by ruthenium and rhodium 31,55,59,72,106). In the reduction of 4-methyl-1-cyclohexenyl ether, the order of decreasing hydrogenolysis to give methylcyclohexane was established as Pt Ir > Rh > Os Ru = Pd (52). 

A quantitative comparison of metals in the hydrogenation of vinyl ethers has been made, The extent of hydrogenolysis in hydrogenation of l-ethoxy-3-methylcyclohexene decreased in the order Pt Os > Rh Ir > Pd > Ru U24e)-, in the case of ethyl 4-methyl-1-cyclohexenyl ether, the order was Pt Ir > Rh > Os Ru Pd (124d). In ethanol, ketal formation is a... 

Under comparable conditions the submitters found that the corresponding dihydropyran derivatives were similarly obtained by the condensation of acrolein with methyl vinyl ether in 80-81% yield, with ethyl vinyl ether (77-85% yield), with w-butyl vinyl ether (82% yield), with ethyl isopropenyl ether (50% yield), and with w-butyl cyclohexenyl ether (40% yield). Other <, /3-un-saturated carbonyl compounds that have thus been condensed with ethyl vinyl ether are crotonaldehyde (87% yield), meth-acrolein (40% yield), a-ethyh/3-n-propylacrolein (54% yield), cinnamaldehyde (60% yield), /3-furylacrolein (85% yield), methyl vinyl ketone (50% yield), benzalacetone (75% yield), and benzal-acetophenone (74% yield). 

This type of coordination is useful for highly stereoselective syntheses of cyclopropane derivatives. Reaction of A -cyclohexenyl methyl ether with the Simmons-Smith reagent gives CM-2-bicyclo[4.1.0]heptyl methyl ether without the trans isomer 103). The Simmons-Smith reaction with 7-tCT f-hutoxynorbornadiene gives syn-exo- IV) and syn-endo isomer (V) without the anti isomers 260). 

The products of the asymmetric alkylation have been used as key building blocks in syntheses of morphanes, phyllanthocin, and periplanone B natural products. In the case of the synthesis of the morphane skeleton, a phenolic nucleophile was reacted with cyclohexenyl methyl carbonate and the resulting ether was subjected to a europium-induced Claisen rearrangement followed by an intramolecular aldehyde-ene reaction to generate the key tricyclic intermediate. Scheme 27 [56]. 

The acrylate Is adds to cyclopentadiene (2) affording the corresponding adduct 3s with a d.r. >99.5 0.5, and its addition to 1.3-butadiene in the presence of titanium(lV) chloride produces the (7 )-cyclohexenyl ester in excellent chemical and optical yields (98% d.r. >97.5 2.5)17. This crystalline acrylate constitutes the first example of a dienophile bearing an auxiliary fulfilling most of the precited prerequisites. The increased efficiency exhibited by Is vs. lr is caused by the fact that the ether side chain is forced closer to the acrylate by the methyl group at C-10. 

The 4-methoxy group present in the des bases C and D may be present in tazettine itself or introduced in the course of the methylation with dimethyl sulfate. Kondo and co-workers preferred the latter alternative they formulated tazettine as an enol which was converted to an enol methyl ether in the preparation of methyltazettine methiodide. Such a concept is inadmissible since 0-acetyltazettine does not have the spectral or chemical properties of an enol acetate. Further, the hydrolytic conditions required to convert methyltazettine methochloride to tazettine methochloride (in poor yield) were more vigorous than those usually required for the hydrolysis of a 1-cyclohexenyl methyl ether. It is evident then that the methoxyl group of tazettine is in the 4-position of CXXV, and it follows that the double bond is located in the 2,3-position. 

As an example, treatment of allyl as-5-methyl-2-cyclohexenyl ether (5) with butyllithium in tetrahydrofuran at —85 JC affords the [2,3] Wittig product 6. which is then transformed to the oxy-Cope product 7 by reaction with potassium hydride in the presence of 18-crown-6. However, this two-step sequence is accompanied by the tandem process 5 -> 6 -> 7. since reaction of 5 gives a 62 14 mixture of 6 and 7. The overall transformation proceeds with exclusive cis selectivity1178. 

The conversion of the cyclohexenyl methyl carbonate shown, to an ether with loss of carbon dioxide in preference to trans-esterification was effected by heating with phenol and small quantities of Pd2(dba)3 and 1,4-bis(diphenylphosphino)butane in tetrahydrofuran at 60°C during 12 hours to give an 82% yield of cyclohex-2-enyl phenyl ether (ref.34). 

An additional method of ACEC synthesis was based on hydroxybenzoic acids as the starting materials [32]. The synthesis starts from esterification of the acid with 3-cyclohexenyl-1-methyl alcohol. The following hydroxybenzoic acids were used 2-hydroxybenzoic (salicylic), 2,4-di-hydroxybenzoic ( 3-resorcylic) and 3,4,5-trihydroxybenzoic (gallic) acid. The phenolic hydroxyls in the cy-clohexenylmethyl esters were transformed in glycidyl ethers in the usual way (reaction with excess ECH followed by dehydrochlorination). Eventually, epoxidation with PAA was carried out (Scheme 51). The epoxide groups content in the ACECs thus prepared was above 85% of the calculated value. 

Flexible epoxy resins were synthesized by the polymerization of epoxy compounds in the presence of an unsaturated alcohol (Scheme 56) followed by the epoxidation of the double bond with PAA. If a glycidyl ether of a cyclohexenyl ring-containing alcohol is used as the epoxy compound, a polyether-epoxy resin is obtained (Scheme 57). The polymerization of 3-cyclohexenyl-1-methyl glyci-... 

A 10 3 2 mixture of butyl vinyl ether, EtjN, and cyclohexenyl triflate treated with a little Pd(OAc)2 in DMSO, and heated to 60-5° with stirring for 3h - 1-(1-butoxyethenyl)cyclohexene. Y 87%. Significantly, vinylation takes place at the a-position (whereas with aryl triflates a mixture of regioisomers is obtained). F.e. with both cyclic and alicyclic enol triflates, and conversion to methyl a,(3-ethyleneketones s. C.-M. Andersson, A. Hallberg, J. Org. Chem. 54, 1502-5 (1989). 

Methylcyclohexanone diethyl acetal heated with 0.1% anhydrous p-toluenesulfonic acid at 100-110° under ca. 100 mm pressure with distillation of the resulting ethanol 4-methyl-1-cyclohexenyl ethyl ether. Y 82%. F. e. s. U. Schmidt and P. Grafen, A. 656, 97 (1962). 

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