Diastereotopic groups

The Use of Diastereotopic Groups as a Probe for the Determination of the Configurational Stability at the Tin Atom... 

Organotin compounds with diastereotopic groups can be used to determine how rapidly tin inverts its configuration. This is shown below if a racemic mixture M + M is examined by NMR, two distinct signals are expected for the diastereo-... 

The determination of the Concentrations in pyridine [N] which cause the coalescence of the signals of the diastereotopic groups of a 0.262 M solution methylneophyl-t-butyltin bromide (6) and of 0.332 M solution methylneophylphenyltin chloride (3) at 22 °C at respectively 60, 100 and 270 MHz shows12) that the k2 term is much smaller than the k3[N] term. From these results, it is clear that the inversion of the configuration of the metal atom of triorganotin halides is second-order in the nucleophile pyridine. An analogous rate equation has been found for the racemiza-tion of triorganosilicon halides 29), for which the activation entropy AS is about —50 e.u. Several mechanisms with increase of coordination number 30) can be proposed to account for this second order in the nucleophile 31) ... 

The general subject of asymmetric synthesis has been reviewed extensively (1-5). The term asymmetric synthesis has been defined in more than one way (1,4) however, a useful definition is the one given by Morrison and Mosher (1) a process which converts a prochiral unit [refs. 6 and 7] into a chiral unit so that unequal amounts of stereoisomeric products result. The stereoisomeric products may be enantiomeric or they may be diastereomeric. The substrate molecule must contain either enantiotopic or diastereotopic groups or faces (8,9), since the attack of a reagent at equivalent groups or faces cannot lead to isomeric products. 

The pyramidal inversion of phosphorus was studied by dynamic NMR spectroscopy using the H signals of N—Me diastereotopic groups in (60) and P signals in Z- and -diastereomers of (61). Kinetics at coalescence temperature revealed the value of AG to increase in the order of increasing electronegativity Si < Sn < Ge <82JOM(224)247>. 

Assignment of diastereotopic groups (e.g., (3-protons of aromatic amino acids, methyl groups in Val or Leu, both a-protons of Gly, pro-R or pro-5) is necessary for reliable conformational analysis but it is normally not important for proof of the constitution (Section 7.5.3). 

Finally, special descriptors, re and si, are logically required for achirotopic diastereotopic groups as in X(AAFF). The reason has already been explained in conjunction with two-dimensional "pscudoasymmetric figures in Section 1.1.2.2.2. 

In retrospect, it seems unfortunate that in 1971 Morrison and Mosher8 generalized the definition, while keeping the term, an asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereoisomeric products arc produced in unequal amounts ( Footnote The substrate molecule must have either enantiotopic or diastereotopic groups or faces) . Obviously the phrase "an achiral unit in an ensemble of substrate molecules is too inexact and requires a great deal of additional explanation, which was partially given by the footnote (note that molecule, i.e., singular, was used ). Currently, the Morrison-Mosher term appears to be equivalent to stereoselective reaction. Unfortunately, this term was only defined in the modem sense by Izumi in 1971, i.e., in the same year the Morrison-Mosher definition was published. 

In many other cases besides the most intensely investigated MTPA derivatives, addition of shift reagents can increase the differences in chemical shifts of diastereotopic groups, detectable in all kinds of nuclei. Some examples are mentioned in the respective sections. 

Asymmetric bond disconnection is less frequently employed than asymmetric bond formation for the synthesis of chiral, nonracemic compounds. The substrates for these transformations contain either enantiotopic (diastereotopic) hydrogen atoms or enantiotopic (diastereotopic) functional groups. In some cases the classification of a given transformation of such a substrate as asymmetric bond disconnection or bond formation is somewhat arbitrary. Thus, enantiotopic and diastereotopic group differentiation is also described at appropriate places in various sections but more specifically in part B of this volume. 

Enantiotopic functional group differentiation is the domain of enzymes, whose use for such purposes is now well established as a method of broad applicability. This topic has been reviewed extensively 84 90-90a. The utility of nonenzymatic methods to achieve enantiotopic group differentiation is less well established. This topic has also been reviewed3. Diastereotopic group differentiation thus far involves substrates with chiral amide groups. 

Constitutionally Heterotopic and Diastereotopic Groups Differ in all scalar properties and are distinguishable under any conditions, chiral or achiral. Asymmetric molecules cannot contain homotopic or enantiotopic groups, only diastereotopic or constitutionally heterotopic groups. 

Table 2. Chemical Shift Differences (ppm) of Diastereotopic Groups in Compounds 75 and 76...

A—B and C-C with a closely related complex containing diastereotopic groups on C-C. 

Chiral molecules may be studied by a great many techniques. Without optical resolution, chiral structures can be detected by the magnetic nonequivalence of diastereotopic groups in NMR spectroscopy. Diaste-reoisomeric pairs of enantiomers, with and without separation, as well as resolved optically active compounds can be used for the investigation of stereochemical problems. Although stereochemical information can be obtained in many ways, the chiroptical properties of optically active compounds constitute an additional handle" for assignment and correlation of configuration that is not available to optically inactive probes. 

---