1.6- Disubstituted cyclohexenes

This method provides a useful route to ds-3,5-disubstituted cyclohexenes. However, the original method for decomplexation to give 4 proceeds in low yield, and the conditions are too drastic for sensitive functional groups. A novel demetallation of complexes such... 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

Diethylaminobutadiene reacts with ethyl acrylate and exclusively gives 3,4-disubstituted cyclohexene product (Scheme 13a) [13, 14], The reaction of... 

Butadiene with an electron donating group at the 2-position has the largest HOMO amplitude on C, (Scheme 15). A bond forms between Cj of the dienes and Cp of the dienophiles (Scheme 17b). This is in agreement with the exclusive formation of 1,4-disubstituted cyclohexene in the reaction of 2-ethoxybutadiene with methyl acrylate (Scheme 13b) [13, 14]. 

Most of the studies to date have employed either palladium [222—229] or platinum [220,224,226,228—235], commonly as Adams reduced platinum oxide, although nickel [228,236,237], rhodium [238,239], ruthenium [239], iridium [239], iron [237] and tungsten [237] have also been used. Many of these studies have been concerned with the stereochemistry of the hydrogenation of disubstituted cycloalkenes. Table 32 shows some typical results for the platinum- and palladium-catalysed hydrogenation of disubstituted cyclohexenes. Table 33 shows comparative results for the hydrogenation of 1,4-dialkylcyclohexenes over palladium, platinum and rhodium catalysts. 

In a related reaction, stereochemical control during epoxidation of A4- .v-l, 2-disubstituted cyclohexenes 141 with MCPBA depends upon the hydroxyl functionality195. A free alcohol (141a) or an acetate (141b) affords. vyw-cpoxides exclusively. Epoxidation of a t-butyldimethylsilyl ether (141c) gives predominantly the rmtf-cpoxide (54%). 

It became apparent early on that compounds of the 1,2-disubstituted cyclohexenes allow exploitation of a wide range of synthetic opportunities, leading to their frequent use in natural product synthesis the application of chemo-synthetic routes for selected monoterpenoid indole alkaloid alone are summarised here [86]. 

Here we are primarily concerned with the fact that this ortho -adduct may occur in the form of two diastereomers. The diastereomers are formed as a 57 43 cis/trans-mixtme in the absence of A1C13, but a 95 5 cis/trans-mixture is obtained in the presence of A1C13. In the latter case, thus, one is dealing with a Diels-Alder reaction that exhibits a substantial simple diastereoselectivity (see Section 11.1.3 for a definition of the term). Here, the simple diastereoselectivity is due to kinetic rather than thermodynamic control, since the preferentially formed ds-disubstituted cyclohexene is less stable than its irans-isomer. 

The versatility of the 1,4-disubstituted cyclohexene derivatives as synthesis intermediates, with emphasis on stereo control, was demonstrated by substitution procedures. Direct Sn2 with malonate anion proceeds selectively for Cl with inversion, and Pd°-catalyzed substitution also proceeds selectively at Cl, but with retention. A second substitution, Pd°-catalyzed, using dimethylamine in this case, leads to replacement of the acetate with retention (Scheme 24). ... 

The raws-3,4-disubstituted cyclohexene 84 affords the corresponding 2-oxazolidinone 9 by treatment with bromonium dicollidine perchlorate. 

Formation of the cis-oxirane 11 in the case of 1,6-disubstituted cyclohexenes can be justified by the occurrence of torsional strain (Eq. 2a). ... 

The Stereochemistry of the Hydrogenation of Cyclic Olefins The hydrogenation of disubstituted cyclohexenes and of substituted methylenecyclohexanes is generally observed to yield a mixture of the cis- and trans- isomers of the corresponding cyclohexane (see Section II, A). The isomer composition is a function of hydrogen pressure (13, 15, 20) (see Fig. 17) and of the nature and position of the substitu-... 

Garbisch has demonstrated, from the application of NMR spectroscopy, that many 1,6-disubstituted cyclohexenes existed predominantly in the conformer having the C6-substituent axial [4]. Garbisch also noted that the 6-equatorial substituent in 1-arylcyclohexenes was held more nearly in C2-C1-C6 plane (due to conjugation effects) than the 6-equatorial substituent in 1-alky Icy clohexenes. The interaction between the aryl group and C6-equatorial substituent leads to a... 

The same calculated hydrogenation energy must be used for both o- and p-xylene. While o-xylene might be better modeled by [2 (cyclohexene) + 1 Affjj2 (1,2-dimethylcyclohexene)], there is no measured enthalpy of formation value for the disubstituted cyclohexene. 

This was eventually obtained by replacing the silicon reagent with a boron one, as described in Fig. 10 [47]. Here, treatment of 1 with a mild LA gave the unstable imine 9 that underwent reaction with a variety of differently boron-disubstituted cyclohexen-2-yl... 

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