Cyclohexane derivatives alkyl, conformation

Other examples of the formation of six-membered rings by means of an intramolecular alkylation of an ester enolate are given in Table 7. Entry 6, i.e., stereoselective transformation of the epoxy ester into the cyclohexane derivative, should be discussed briefly as a representative for the other cases. The probable reason for the unexpectedly high selectivity i.e., the nonappearance of the diastereomer 8, can be demonstrated by the two transition-state-like conformations 9 and 10. 9 displays a very severe 1,3-diaxial interaction in comparison to 10, thus, formation of the diastereomer 7 from conformation 10 is highly favored113. 

Recently, Crabb, Turner, and Newton (68) have observed that perhydropyrido-[1.3]oxazine exists as a =9 1 mixture of the trans and the cis forms 97 and 98. The cis form 98 has two anomeric effects (-2.8 kcal/mol), two gauche forms of butane (1.8 kcal/mol) and one gauche form of -propyl ether (0.4 kcal/mol) whereas the trans form 97 has only one anomeric effect (-1.4 kcal/ mol). On that basis, the trans form 97 should be more stable than the cis form 98 by about 0.8 kcal/mol, in agreement with the experimental result. Katritzky and co-workers (69) have also shown that 1-oxa-3,5-diaza and 1,3-dioxa-5-aza cyclohexane derivatives exist respectively in the conformations 99 and 100. With an alkyl group in the axial orientation, both conformations gain two anomeric effects. 

In cyclohexane derivatives with larger alkyl substituents, the strain caused by 1,3-diaxial interactions is even more pronounced. The conformation of tert-butylcyclohexane with the rm-butyl group equatorial is estimated to be approximately 21 kJ moP more stable than the axial form (Fig. 4.20). This large energy difference between the two conformations means that, at room temperature, 99.99% of the molecules of tert-butylcyclohexane have the r rt-butyl group in the equatorial position. (The molecule is not conformationally locked, however it still flips from one chair conformation to the other.)... 

By analogy with acyclic aldehydes and ketones, an alkyl group at C(2) of a cyclohexanone would be expected to be more stable in the equatorial than in the axial orientation. The equatorial orientation is eclipsed with the carbonyl group, and corresponds to the more stable conformation of open-chain aldehydes and ketones. By analogy to derivatives of cyclohexane, an alkyl group at C(2) would also be expected to be more stable in the equatorial orientation, owing to decreased... 

Among several chiral cyclic and acyclic diamines, (R,R)-cyclohexane-l,2-diamine-derived salen ligand (which can adopt the gauche conformation) was most effective in providing high enantioselectivity [38]. Further, the introduction of substituents at the 3,4, 5 and 6 positions on the aromatic ring of catalyst 39c was not advantageous, and resulted in low enantioselectivity [32,37,39]. The metal ions from first-row transition metals - particularly copper(II) and cobalt(II) - that could form square-planar complexes, produced catalytically active complexes for the asymmetric alkylation of amino ester enolates [38]. 

For the 1,4-dithiane skeleton, two S-alkyl-l,4-dithianium salts 72 and 73 were studied by variable temperature NMR spectroscopy in the solid state (13C CP-MAS) (99JMS93) line shape variations were attributed to the conformational motion of the six-membered ring (cf. Scheme 26). Also, the vibrational frequencies of the 1,4-dithiane derivative were analysed in detail it was corroborated that the molecule exists in the C2h configuration similar to the chair form of cyclohexane (99SA(A)121). 

Enolates derived from cyclic compounds such as cyclohexane carboxylic acid or cyclohexane carboxalde-hyde generate enolates that are unique. These enolates have an exocyclic double bond that can exist as ( ) and (Z) isomers. The facial and orientational bias in alkylation and condensation reactions of such enolates is influenced by the conformation of the ring it is attached to. Alkylidene cyclohexane enolates show a preference for equatorial attack, just as cyclohexanone derivatives do (sec. 4.7.C,D). 

The temperature-dependent NMR spectra of cyclohexane itself were investigated more than 25 years ago by NMR using several methods and solvents The barrier for chair-to-chair interconversion was determined to be 10.25 kcal mol Subsequently, simple alkyl-substituted derivatives were examined by NMR, for example methylcyclohexane and 1,2-dimethylcyclohexane (Figure 9). The chemical shifts observed in the low-temperature region are in line with the steric interactions and the conformational increments discussed in Section ILB.4. 

Let us consider the bromination of (i )-4-f rf-butylcyclohexene. Recall that in derivatives of cyclohexane in which interconversion between one chair conformation and the other is not possible or is severely restricted, the trans diaxial product is isolated. If a cyclohexane ring contains a bully alkyl group, such as fert-butyl (Section 2.6B), then the molecule exists overwhelmingly in a conformation in which the fert-butyl group is equatorial. Reaction of bromine with enantiomerically pure (R)-4-fert-butylcyclohexene occurs at both faces of the six-membered ring. Because bromine atoms must add in an axial manner, each bromonium ion intermediate reacts with bromide ion to give the same product. In the favored chair conformation of this product, fert-butyl is equatorial, the bromine atoms remain axial, and only a single diastereomer is formed. 

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