Introduction Esters

Esters are one of the more common groups used in carbohydrate chemistry^^, since their early exploitation as protecting groups for alcohols which can be selectively removed under various conditions. Esters are similarly exploited in many synthetic processes^

Figure 2.1 illustrates the general structure of the ester group and the nomenclature that I employ in this dissertation.

Alkyl to oxygen bond Acyl to oxygen bond

Nomenclature fo r the conformational analysis o f ester group. Figure 2.1

The conformational analysis of the ester group is concerned with the populated conformation o f both the acyl-to-oxygen and the alkyl-to-oxygen bonds and the systems selected were the simplest: acetates ( R - CH3) and formates (R -H ).

The different possible conformations around the two bonds are shown in Figure 2.2 with the nomenclature that we propose to use. The alkyl-to-oxygen bond offers the possibility to study the ^gauche/eclipsed-anti conformational equilibrium and research has centred on sec-alkyl esters (especially acetates), because of previous eclipsed conformation studies"^^. The acyl-to-oxygen bond offers the possibility to study the cis(Z)-trans(E) equilibrium, and formates were the simple esters chosen for this purpose.

The introduction indicates why we use the term ±gauche/eclipsed to describe the range of H-C-O-Ac torsion angles from -60° to +60° for the alkyl-to- oxygen bond. Furthermore, with the acyl-to oxygen bond, for convenience in

writing and to avoid confusion over the name anti which has been used, we decided to follow the cis trans nomenclature employed by Eliel and many other authors^^. ,2\\' ^ Gauche/KclipscdZ-Gauche— Trans + (iauche/Eclipsed/-Gauche— ( i s Anti— Trans Anti— ( i s

7 he different conformational possibilities in esters.

Figure 2.2

Our interest in the alkyl-to-oxygen bond is related to previous investigation centred on ±gauche edip.sed and anti conformations in the saturated C-O bonds o f methyl ethers. The analysis o f the equilibrium between these conformations was well defined by Anderson et in a range o f methoxy compounds. When we turned our attention to esters, a previous investigation by Dunitz^^, on the basis o f a search in Cambridge Crystallographic Database^, showed the possibility o f finding further new information about the tendency o f saturated C -0 bonds to adopt an eclipsed conformation. I would like to review his investigation and take a different view o f a set o f structures now nine times larger than was available to Dunitz. An initial approach was carried out by Anderson and Nasser^^ in acetates but I want to expand this and extend it to formates.

The conformational analysis of acyl-to-oxygen bonds was a much-visited topic o f interest at the end of the twentieth century. IR^^, NM R^\ electron diffraction^^ and especially ab initio calculations at different levels of theory^^, are among the techniques exploited.

It has been established that cis is by far the preferred conformation in acyl-to-oxygen bonds in esters, and different explanations have been offered;

i) Dipole-Dipole: Interaction between the dipole in the C =0 bond and at the alkyl oxygen, make the cis less polar and more stable^^.

J

ii) The cis conformation has extra stabilisation due to n-o*c=o overlap involving an oxygen non-bonding pair of electrons antiperiplanar to the C =0 bond. Electrons of the alkyl oxygen are already involved with the 7c-bond due to the non-bonding 7i*-symmetry, which is why the 0-C (=0)R structure is planar. Only the oxygen o-lone pair is available and with the correct symmetry to overlap with the antibonding orbital a*c=o of the C =0 bond^"^, provided the conformation is cis.

iii) Repulsive interactions between R and R' groups (especially important in largest acetates) and between lone pairs on the oxygen atoms are the reasons reported for the instability o f the trans conformation^"^.

The situation for the acyl-to-oxygen bond seems clear in acetate or bigger esters. In formates however, there are quite a few points o f uncertainty and I hope to contribute to their resolution with a series o f investigations.

The techniques used in our search vary with the physical state o f the esters. The solid state has been investigated with a statistical analysis o f crystal structures retrieved from CCDB. Gas phase has been approached with the help o f theoretical calculations, mainly Molecular Mechanics (MM3 and MM2), but some of the stereotype compounds have been calculated using ab initio M O methods. The study in solution has been carried out by NMR and since spectra are temperature-dependent, NMR at various temperatures has yielded population

conformations and the thermodynamic parameters involved in their

interconversion.

The investigation o f ester conformations divides into two parts. The first is the investigation o f acetate esters and concentrates mainly on whether the alkyl-to-oxygen bond prefers to be ±gauche/eclipsed or anti. The second part, after applying the results from the first part for the alkyl-to-oxygen bond to formate esters, focuses on the question of the cis-trans conformational equilibrium for the acyl-to-oxygen bond.

2.2 Acetates

2.2.1 Results and discussion

In acetates R-0-C(=0)CH3, the probability o f the trans conformation for the acyl-to-oxygen bond is very low due to the repulsive interactions between the CHa and the alkyl group (R). In crystal structures, for example, over 6853 general examples, we have found only 13 with the trans conformation^^. Furthermore, for methyl acetate, the cis/trans enthalpy difference is 8.5 kcal/moP^. For these reasons we restrict our studies of acetates to the alkyl-to-oxygen bond, as is now described.