Transition-state structures Subject

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

A high degree of stereoselectivity can be realized under chelation control, where an oxygen atom of an ether function (or more generally a Lewis base) in the a-, P- or possibly y-position of carbonyl compounds can serve as an anchor for the metal center of a Lewis acid. Since Cram s pioneering work on chelation control in Grignard-type addition to chiral alkoxy carbonyl substrates [30], a number of studies on related subjects have appeared [31], and related transition state structures have been calculated [32], Chelation control involves Cram s cyclic model and requires a Lewis acid bearing two coordination sites (usually transition metal-centered Lewis acids). 

Physical organic chemists have used isotope effects for years to give information on mechanisms and transition state structures, and the interested reader should consult standard books on the subject (91, 92). It was only In 1975, however, when Northrop discovered the way to combine deuterium and tritium isotope effects on V/K to obtain an estimate of the intrinsic isotope effect on the bond-breaking step, that isotope effects became a practical tool for the enzy-mologist (93). We give a quick sketch of the methods here, but the reader may wish to consult other recent reviews (94 -96). 

The subject of laser interactions with molecular processes has generated great interest both experimentally and theoretically. This interest has been enhanced by the possibilities for laser-catalyzed chemical reactions, isotopic selectivity, and perhaps even the determination of the transition state structure. The degree of success in this area has been limited by the extreme difficulties of the experiments involved and also the lack of simple and qualitatively accurate theoretical models that can be applied to a wide range of systems. 

The large number of research programs aimed at the syntheses of steroids produced a phenomenal wealth of reaction methods for organic synthesis. The development of the asymmetric proline-catalyzed Robinson annulation reaction for the preparation of the Wieland-Miescher ketone (36, Equation 3) in the early 1970s [41] is noteworthy and marks an important milestone for catalysis by small organic molecules. Asymmetric amine-catalyzed aldol reactions represent an additional variant of the stereoselective aldol addition reaction. The mechanism of the proline-catalyzed aldol addition reaction has been the subject of extensive debate, but the general consensus, based on recent mechanistic studies and quantum mechanical calculations, supports the notion of the involvement of a single amino acid molecule in the transition state structure (39, Scheme 4.4) [42]. 

Gosh independently reported another anti-selective aldol addition process employing aminoindanol-derived esters 114 (Equation 11) [72]. These were subjected to enolization with excess TiCl, and Hiinig s base to furnish titanium 2-enolates, as determined by NMR spectroscopy. Addition reactions with a variety of aliphatic and unsaturated aldehydes, precomplexed with TiCl4, furnished the anti aldol adducts such as 116 in 44—97% yields and up to 99 1 anti/syn ratios of diastereomers. The stereochemical outcomes of the reactions have been attributed to chelated Zimmerman-Traxler transition state structures, such as 115. It is interesting to note that benzaldehyde, as the only aromatic aldehyde examined, yielded a 1 1.1 mixture of antijsyn products. 

It is interesting that the molecular structure in the transition state is also subject to a solvent effect. Compared to the gas phase, the solute molecular geometry at the transition state shifts toward the reactant side in aqueous solution the C—N and C—Cl distances... 

Equilibrium structure (geometry) may be determined from experiment, given that the molecule can be prepared and is sufficiently long-lived to be subject to measurement. On the other hand, the geometry of a transition state may not be established from measurement. This is simply because it does not exist in terms of a population of molecules on which measurements may be performed. 

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