Mass Spectrometric Discrimination of Acyclic Stereoisomers via Competing Unimolecular Decompositions

One of the most difficult challenges of structural analysis is to determine the relative stereochemistry of two asymmetrically substituted centers in an acyclic system. Mass spectrometry has long been known (although perhaps not widely recognized) to have the capacity to accomplish this. The subject has been reviewed, most recently a decade ago (1–3). In the intervening time, instrumentation and computational methods have made signal advances, which warrant not only an outline of newer developments but also a discussion of older work in light of current understanding. This article focuses upon the problem of differentiating acyclic stereoisomers having two asymmetrically substituted tetrahedral centers, a category that embraces not only stereogenic carbon atoms, but also other elements, as well (see Chapter 4 (this volume): Unimolecular Dissociation of Organic Ions: Reactions that Reveal Stereochemistry). Consider a molecule with two asymmetric tetrahedral atoms. Each asymmetric center can have two absolute configurations, R or S. The molecule can therefore have four separable stereoisomers. The R,R and S,S isomers (nonsuperimposable mirror images of one another) will have identical spectroscopic properties (except with regard to circularly polarized light), as will the S,R and R,S isomers. Nonsuperimposable mirror images are called ‘enantiomers’. Stereoisomers that are not mirror images of one another (such as R,R and R,S) are called ‘diastereomers’ and will have different spectroscopic properties. Figure 1 illustrates these relationships for the carboxylate anions of the amino acid isoleucine. The general theme, which will be presented here, is that diastereoselection in the unimolecular fragmentations of acyclic ions arises as a consequence of cyclic transition states. The placement of substituents in three dimensions imposes steric constraints on a ring, which can lead to different branching between competing pathways in one stereoisomer relative to another. Accordingly, this article is organized in terms of the size of the cyclic transition state(s) that have been discussed (in successive order: six-, five-, three-, and four-membered cyclic transition states). In some cases, isotopic labeling or theory justifies the inferred transition state; in others, the mechanism remains a subject of speculation. It is possible for molecular symmetry to remove the chirality of a pair of enantiomers. For example, 5,7undecanediol, illustrated in Fig. 2, possesses twofold molecular symmetry, such that the S,R and R,S configurations are superimposable. Therefore, this diol has only three stereoisomers, rather than four. The S,R/R,S isomer is achiral (since it has a plane of symmetry) and is called meso. The R,R and S,S isomers are sometimes called a d,l pair (or, if they are in a 50:50 mixture, the rac diastereomer). 3B2v7:51c GML4:3:1 Emas : 00016 Prod:Type: pp:1212ðcol:fig::NILÞ ED: PAGN: MOHANAT SCAN: