Cyclohexanes tetrasubstituted

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

Such a strategy follows the philosophy of resin capture, as introduced by Armstrong and Keating Keating TA, Armstrong RW. Postcondensation modifications of Ugi four-component condensation products 1-isocyano-cyclohexane as a convertible isocyanide. Mechanism of conversion, synthesis of diverse structures, and demonstration of resin capture. J Am Chem Soc 1996 118 2574-2583. See also Brown SD, Armstrong RW. Synthesis of tetrasubstituted ethylenes on solid support via resin capture. J Am Chem Soc 1996 118 6331-6332. 

If the fluoro-compounds be excepted the results in Tables 4 and 5 can be generalised as follows. Barriers for 1,1-disubstituted cyclohexanes are not consistently different from those of the unsubstituted compound while those in 1,1,4,4-tetrasubstituted cyclohexanes are slightly larger than in cyclohexane itself. ) Barriers to ring inversion in 1,1,3,3-tetrasubstituted cyclohexanes are slightly lower than in cyclohexane while those of 1,1,3,3,5,5-hexasubstituted cyclohexanes are substantially lower. 

Ye have chosen these substitution patterns since they must have axial substituents in any chair conformation, and 1,3 diaxial substituent-hydrogen interactions are expected to be the strongest van der Waals interaction in cyclohexane. We have excluded 1,1,2,2-tetrasubstituted cyclohexanes, since 1,2 interactions are presumably the principal factors in these molecules. 

Scheme 7.1 Enantioselective synthesis of tetrasubstituted cyclohexanes by Michael/ nitroaldol cascade reaction.

When unsaturated fatty acids are subjected to thermolytic cleavage, dimers, polymers and cyclic compounds are produced. The dimers include alicyclic mono-, di-, and triene dehydrodimers, saturated dimers with cyclopentene structures, tetrasubstituted cyclohexanes and bicyclic and tricyclic dimers (Nawar, 1985). Cyclic mononmers exhibit toxicity in experimental animals (Van Gastel et al, 1984), therefore, generation of cyclic monomers at high temperature frying with oils containing polyunsaturated fatty acids should be carefully monitored. 

Sutherland and his co-workers have established that tetrasubstituted cyclohexane epoxides can fulfil a useful role as cationic cyclization initiators." Several alk-3-enyl-2,3-epoxy-3-methylcyclohex-2-enones, e.g. (177), have been successfully cyclized to decalone derivatives, e.g. (178), in good yield on treatment with Lewis acids, and the acetylenic epoxides (179) and (181) have been cyclized in excellent yields to the expected decalin (180) and hydrindane (182) derivatives respectively." ... 

The substitution pattern in the enolate is crucial for the ring size of the cyclization product. Upon reaction with carbene complex 58 /3-substituted lithium enolates 59a H) lead to densely substituted cyclopentanols 60 suggesting a [2-i-2-i-l]cycloaddition pathway. /3-Unsubstituted lithium enolates 59b (R =H), however, form 1,3,3,5-tetrasubstituted cyclohexane-l,4-diols 61 that indicates a [2-I-2-I-1-I-1] sequence [41]. The branching point in the mechanism seems to be intermediate B formed upon addition of the allyl magnesium bromide to penta-carbonylchromate intermediate A. Intermediate B formed from /3-substituted enolates 59a is supposed to undergo an intramolecular carbometallation reaction to give cyclopentanol derivative 60. In contrast, intermediate B originating from... 

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