Conformations acyclic compounds

Acyclic Compounds. Different conformations of acyclic compounds are best viewed by construction of ball-and-stick molecules or by use of Newman projections (see Fig. 1.2). Both types of representations are shown for ethane. Atoms or groups that are attached at opposite ends of a single bond should be viewed along the bond axis. If two atoms or groups attached at opposite ends of the bond appear one directly behind the other, these atoms or groups are described as eclipsed. That portion of the molecule is described as being in the eclipsed conformation. If not eclipsed, the atoms... 

In the main, the physical and chemical properties of saturated and partially unsaturated alicyclic compounds closely resemble those of the analogous acyclic compounds formally derived by cleavage of the carbon ring at a point remote from any functionality. Relatively small, but often significant, differences in properties arise from conformational effects, and from strain effects in small rings, and these differences can be striking in properties which are particularly sensitive to molecular shape. 

The preceding prediction rules are largely restricted to acyclic compounds. But there is also a considerable need for parameter sets enabling the spectroscopist to calculate I3C chemical shifts of conformationally defined cyclic molecules, especially of the cyclohexane type. Methyl-group effects in methylcyclohexanes (100,101) that are to be added to the basic value for cyclohexane itself (8 = 27.3) are listed in Table 29. Analogous methyl-group parameters in tetralins and tetra-hydroanthracenes have been reported (403). 

However, note carefuUy that changing the conformation does not affect the spatial sequence about the chiral centres, i.e. it does not change the configuration at either chiral centre. This seems a trivial and rather obvious statement, and indeed it probably is in the case of acyclic compounds. It is when we move on to cyclic compounds that we need to remember this fundamental concept, because a common mistake is to confuse conformation and configuration (see Box 3.11). 

Eliel E, Wilen SH (1994) Stereochemistry of organic compounds. Conformation of acyclic molecules. Wiley, New York, pp 597-664, chap 10... 

We have already seen other meso compounds, although we have not yet called them that. For example, the cis isomer of 1,2-dichlorocyclopentane has two asymmetric carbon atoms, yet it is achiral. Thus it is a meso compound, cis-1,2-Dibromocyciohcxanc is not symmetric in its chair conformation, but it consists of equal amounts of two enantiomeric chair conformations in a rapid equilibrium. We are justified in looking at the molecule in its symmetric flat conformation to show that it is achiral and meso. For acyclic compounds, the Fischer projection helps to show the symmetry of meso compounds. 

You will see why such detailed conformational analysis of acyclic compounds is so important in Chapter 19 on eliminations where the products of the reactions can be explained only by considering the conformations of the reactants and the transition states. But first we want to use these ideas to explain another bl anch of organic chemistry—the conformation of ring structures. 

The answer to the first point, as you may already have guessed, is that the assumption that the rings arc planar is simply not correct. It is easy to see how large rings can fold up into many different conformations as easily as acyclic compounds do. It is less clear to predict what happens in six-membered rings. 

Diastereoselectivily in compounds without rings is different it is less well controlled, because there are many more conformations available to the molecule. But even in acyclic compounds, rings can still be important, and some of the best dia stereoselectivities arise when there is a ring formed temporarily in the transition state of the reaction. With or without cyclic transition states, in some cases we have good prospects of predicting which diastereoisomer will be the major reaction product, or explaining the diastereoselectivity if we already know this. That is the subject of the next chapter. 

Among the most widespread classes of acyclic compounds to exhibit stereoelectronic control over conformation are acetals. Take the simple acetal of formaldehyde and methanol, for example what is its conformation An obvious suggestion is to draw it fully extended so that every group is fully anti-periplanar to every other—this would be the lowest-energy conformation of pentane, which you get if you just replace the Os with CH2S. 

The proposed schemes for the synthesis of macrobicyclic tris-dioximates have most readily been realized in high yields for alicyclic dioximes, having a cis-conformation both in crystals and in solutions. The change of the acyclic dioxime conformation from trans to cis during complexation decreases the stability of the compounds formed. 

To achieve diastereoselectivity in electrophilic additions to a double bond in acyclic compounds, there must be a facial preference for attack. An A strain provides such an element for conformational control, as exemplified by hydroboration of the alkene shown below.The hydration of a double bond via hydroboration involves (1) anti-Markovnikov addition of the B-H bond, (2) cis addition of the B-H bond, (3) addition of the B-H bond from the less hindered side of the double bond, and (4) oxidation with retention of configuration. 

Usually this antiperiplanar conformation is easy to reach for acyclic compounds, because of the low energy barrier between the conformations. 

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