Bonding Theory and Stereoselection

In a series of communications, Woodward and Hoffmann (1965 Hoffmann and Woodward, 1965 Woodward, 1967) gave a beautifully simple solution to the problem of stereoselection in molecular reactions. 

By molecular reactions, we mean that group of concerted reactions which are neither ionic, nor radical, and which have no mechanism (Rhoads, 1963). The basic idea is that those reaction paths are favored in which orbital symmetry is conserved. Their work quickly provoked contributions from theoreticians and experimentalists alike. Fukui (1965, 1966 Fukui and Fujimoto, 1965, 1966), for example, must be credited with extending their ideas to include heterolytic and homolytic reactions. All of this work will be considered in detail. 

We shall discuss several types of no-mechanism reactions first and some-mechanism reactions second. From an orbital viewpoint, all heterolytic rearrangements would be subsumed under sigmatropic reactions heterolytic substitutions and additions (eliminations) turn out to be versions of cycloadditions (cycloeliminations). Nevertheless, we have retained categories on the basis of mechanism, because these are familiar, and because the trend is from the relatively simple to the complex mechanism. 

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A I Cycloaddition reactions are among the most powerful reactions available to the organic chemist. The ability to simultaneously form and break several bonds, with a wide variety of atomic substitution patterns, and often with a high degree of stereocontrol, has made cycloaddition reactions the subject of intense study. The productive interplay between theory and experiment has resulted in sophisticated models which often allow one to predict reactivity, regioselectivity, and stereoselectivity for given cycloaddition partners. 

It is of interest to investigate the usefulness of this theory to the chemical change involving the interaction between the conjugated systems 56,62,145). Such a-n interactions are frequently stereoselective. The addition to olefinic double bonds and the a, -elimination are liable to take place with the fraMS-mode 146h The Diels-Alder reaction occurs with the cis-fashion with respect to both diene and dienophile. 

Whereas FMO theory correctly predicts the regioselectivity for cycloadditions in simple alkyl-substituted olefinic systems,51,58 extension of similar calculations for cycloadducts (7a,b-lla,b)120 predicts the formation of regioisomer a, although, except in the case of 7 and 8, the b isomer is the predominant one. The differences between prediction and experiment in stereoselectivity have been attributed primarily to double bond rehybridization arising from double bond distortion in bridgehead olefins,142 which also explains their enhanced reactivity.96,120 Also double-bond deformation that will alter the normal mixing of alkyl substituent orbitals with localized rc-bond orbitals may explain the unexpected formation of 8b.120 Attempts to explain the formation of the b isomers, based on a two-step diradical mechanism, also have failed.120... 

If one subscribes to the oxocarbenium-centric theory of glycosidic bond formation [20, 21], it is apparent from Scheme 5.2 that the grounds for stereoselective bond formation are slim. This is because neither of the two possible interconverting halfchair conformers of the oxocarbenium ion (4H5 and 5H4) appear to exhibit any overwhelming steric preference for one face of the system over the other [22],... 

A related method to interpret the diastereofecial selectivities of the reactions of double bonds has been proposed by Dannenberg and coworkers [8, 13, 14,]. Tins method also relies on the 7t frontier orbitals of non symmetrical molecules, and proposes breaking the symmetry of the n or it orbitals due to polarization induced by the substituents. Application of frontier molecular orbital theory, taking into account only the substrate MOs, gives a qualitative trend of stereoselection in a number of nucleophilic (reductions of carbonyl compounds) and electrophilic reactions. 

This chapter is divided into two sections, largely separating stereospecific reactions from the merely stereoselective. The first (Section 5.1) deals largely with stereospecific reactions, and the explanations based on molecular orbital theory for the sense of that stereospecificity. The second (Section 5.2) deals with stereoselective reactions, in which a new stereocentre is created selectively under the influence of one or more existing stereocentres or stereochemical features. The way in which a resident stereocentre controls which of two surfaces of a n bond is attacked is also sometimes a question of how the orbitals interact. The stereospecificity that is such a striking feature of pericyclic reactions is covered in the next chapter. 

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