Conformations ring-flipping

The stereochemical product ratio for the reduction of cyclic ketones by hydrides is affected by the structure of the cyclic ketone and the nature of the hydride used. The reduction of substituted cyclohexanones avoids product interconversion by conformational ring flip because of conformationally locked cyclohexanones. In such cases, axial attack is preferred over equatorial attack. 4-fert-Butylcyclohexanone (6.50) is reduced by NaBH4 and by LiAlH4 to give 86% and 92% of trans-4-fert-butylcyclohexanol (6.51), respectively. Hindered hydrides such as f-BusBHLi show more selectivity. 

An argument similar to that for the hydrolysis of D-gluconolactone leads us to 59 as the final product, wherein the label O18 has been incorporated. The transformation 57 —> 60 is not allowed for the lack of support by the requisite two stereoelectronic effects. Conformational ring flip from 57 to 61 is energy requiring. It may therefore be claimed not to compete with the fast cleavage of 57 to 58 because the latter is supported by two stereoelectronic effects. Let us see the turn of events assuming that the said conformational flip does compete and 61 is indeed formed. 

In cri-l,2-dimethylcyclohexane, one methyl group is axial and the other is equatorial (Rg. 5.38). The conformational ring flip does not alter the structure—the axial methyl becomes equatorial, and the equatorial methyl becomes axial. The equilibrium constant between these two equivalent compounds must be 1. 

We have seen that alkanes are not locked into a single conformation Rotation around the central carbon-carbon bond m butane occurs rapidly mterconvertmg anti and gauche conformations Cyclohexane too is conformationally mobile Through a process known as ring inversion, chair-chair mterconversion, or more simply ring flipping, one chair conformation is converted to another chair... 

The most important result of ring inversion is that any substituent that is axial in the original chair conformation becomes equatorial in the ring flipped form and vice versa... 

The methyl groups are described as cis because both are up relative to the hydrogen present at each carbon If both methyl groups were down they would still be cis to each other Notice that ring flipping does not alter the cis relationship between the methyl groups Nor does it alter their up versus down quality substituents that are up m one conformation remain up m the ring flipped form... 

Conformational inversion (ring flipping) is rapid in cyclohexane and causes all axial bonds to become equatorial and vice versa As a result a monosubstituted derivative of cyclohexane adopts the chair conforma tion in which the substituent is equatorial (see next section) No bonds are made or broken in this process... 

Ring inversion (Section 3.9) Process by which a chair conformation of cyclohexane is converted to a mirror-image chair. All of the equatorial substituents become axial, and vice versa. Also called ring flipping, or chair-chair interconversion. 

What effect does a ring flip have on substituent positions Do all of the substituents change position or only certain ones If the latter, then which substituents are affected Obtain the energies of the two conformers. Which conformer is preferred Why ... 

Make a sketch of each decalin isomer, and label the orientation of the bridgehead hydrogens with respect to each ring (equatorial or axial). Build a plastic model of each isomer and determine its conformational flexibility (a flexible molecule can undergo a ring flip, but a locked molecule cannot). Is flexibility responsible for stabihty ... 

H321). Tliese radical cations exist in a nonplanar conformation. With fra s-3,4-dimethyl substituents, the barrier to ring flip was estimated to be >5 kcal/mol. In connection with reactions of thiirane with the thiirane radical cation, ab initio calculations were reported on the 1,2-dithietane radical cation (93JA12510). 

Because chair cyclohexane has two kinds of positions, axial and equatorial, we might expect to find two isomeric forms of a monosubstituted cyclohexane. In fact, we don t. There is only one methylcyclohexane, one bromocydohexane, one cycJohexanol (hydroxycyclohexane), and so on, because cyclohexane rings are confbnnationally mobile at room temperature. Different chair conformations readily interconvert, exchanging axial and equatorial positions. This interconversion, usually called a ring-flip, is shown in Figure 4.11. 

Thomson fOV Click Organic Interactive to learn to recognize the most stable conformations of cyclohexanes following ring-flips. 

Chair cyclohexanes are conformationally mobile and can undergo a ring-flip, which interconverts axial and equatorial positions. Substituents on the ring are more stable in the equatorial position because axial substituents cause 1,3-diaxial interactions. The amount of 1,3-diaxial steric strain caused by an axial substituent depends on its hulk. 

A A trisubstituted cyclohexane with three substituents—red, yellow, and blue—undergoes a ring-flip to its alternative chair conformation. Identify each substituent as axial or equatorial, and show the positions occupied bv the three substituents in the ring-flipped form. 

Active Figure 17.20 Dehydrochlorination of menthyl and neomenthyl chlorides, (a) Neomenthyl chloride loses HCI directly from its more stable conformation, but (b) menthyl chloride must first ring-flip before HCI loss can occur. The abbreviation "Et represents an ethyl group. Sign in at www.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Figure 27.11 Steroid conformations. The three six-membered rings have chair conformations but are unable to undergo ring-flips. The A and B rings can be either cis-fused or trans fused.

Ring-flip (Section 4.6) A molecular motion that converts one chair conformation of cyclohexane into another chair conformation. The effect of a ring-flip is to convert an axial substituent into an equatorial substituent. 

EXERCISE 6.30 Below you will see one chair conformation of a substituted cyclohexane. Draw the other chair (i.e., do a ring flip) ... 

Figure 5.20 trans- 1,2-Dimethylcyclohexane has no plane of symmetry and exists as a pair of enantiomers (a and b). [Notice that we have written the most stable conformations for (a) and (b). A ring flip of either (a) or (b) would cause both methyl groups to become axial.]... 

Similar correlated rotations are observed in 1,1-diarylalkenes [5 Z = CH2] (Kaftory et al., 1990) and benzophenones [5 Z = O)] (Rappoport et al., 1990). A key feature of the pathway for conformational change in the benzophenones is that maximum v overlap is maintained between the carbonyl group and one of the aromatic rings, so that a one-ring flip pathway, [5]<— [5 ], is strongly preferred. The observed structure set... 

Lindner (171) developed his own tt-SCF MO force field that is similar to MMPI in construction. This program was applied to simulate racemization of metacyclophane (48) and hexahelicene (50). In metacyclophane the m-phenylene ring flips readily at room temperature. Two mechanisms can be conceived one operates by way of a high steric energy conformation (48b) the other involves a biradical intermediate (49). The calculated activation energies are 17 and 32 kcal/mol, respectively. The experimental value is 17.7 kcal/mol, in accord with the first mechanism (172). The structures and energies of seven types of cyclophane have been calculated (172). 

The chair is not the only conformation that cyclohexane might adopt. An alternative boat conformation is attained if the ring flip-type process is confined to just one carbon. The name boat comes from the similarity to boats formed by paper... 

The ring flipping conformational mobility in the unsubstituted compound cyclohexane has little practical significance but, when the ring is substituted, we have to take ring flip into account, because one particular conformation is usually favoured over the other. 

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