Reactive asymmetry

R.J. Beuhler, Jr. and R.B. Bernstein, Crossed-beam study of the reactive asymmetry of oriented methyl iodide molecules with rubidium, J. Chem. Phys. 51, 5305-5315 (1969). 

An important subject of this paper is that of reagent preparation and stereoselectivity. Experimental techniques for production of oriented (and of aligned) molecules and their theoretical description are outlined. Reactive asymmetry experiments using oriented molecule beams are briefly reviewed, and new approaches described. Results are presented of recent experiments which take advantage of the inherent mutual orientation of the molecules in a van der Waals complex, i.e., "precursor geometry-limited" bimolecular reactions. Finally, a new technique is described for real time, picosecond, clocking of the collision complex in such bimolecular reactions. Results are reported for the time-dependent birth of OH from H + CO2. 

The first such "reactive asymmetry" experiments succeeded in demonstrating the orientation dependence of the reactivity of CH3I with alkali atoms [25] ... 

Large differences in reactivity were observed for "heads" vs. "tails" orientations. However, the results were only qualitative and no useful theoretical framework for describing the reactive asymmetry was yet available. 

Similarly resolved rotational states (in oriented molecule beams) have been reported independently [56]. Elegant reactive asymmetry measurements have been carried out with oriented NO and N2O molecules, as reviewed in Ref. 47. In the chemiluminescent (GL) reaction of oriented N2O with Ba[57a], i.e.,... 

New UCLA experiments [62] represent a test of this concept, and demonstrate by a purely physical method the degree of orientation of an "oriented molecule beam", hitherto inferred from crossed molecular beam reactive asymmetry experiments. (The only related observations are those of Ref. 63 in which a partially state-selected and oriented beam of CH3I was subjected to UV photoionization and the anisotropy of the photoelectron angular distribution measured.)... 

So far we have discussed the approach motion of the reactants. But there are usually other requirements, besides the closeness of the approach, for a reaction to take place. In particular, there may be steric requirements, some configurations of the colliding molecules may be more conducive to reaction. A direct experimental verification of the steric requirement can be obtained using oriented reactant molecules. The experiment allows the determination of the reactive asymmetry or the relative reactivity for the two configurations, say... 

Here f and u stand for favorable and unfavorable alignment configurations (CH3I molecules have been oriented by the use of a specially designed configuration of electrical fields). For nearly head-on b 0) collisions the experimental reactive asymmetry is shown schematically in Figure 1.4. See also Figure 10.1. 

The simplest intuitive idea of an atom ora group being in the way ofthe reaction corresponds to a barrier that has a constant height Eq for all approach angles y < Yo, and is infinitely repulsive otherwise. Then yniax = Yo and the cone of acceptance is -independent. This model for o(y) is simpler than Eq. (3.36) but captures well the idea of a steric hindrance and the reactive asymmetry. It leads to a steric factor p given (1 — cos yo)/2. We expect the size of molecules to... 

In the laboratory, the well-defined direction is that of the initial velocity v. Therefore the laboratory orientation angle yl is defined as the angle that the axis of the molecule makes with respect to v. For low impact parameters the two angles are essentially the same because R is essentially in the direction of v and the collision is nearly head on. Otherwise, a transformation is needed. Implicit in such a transformation and in our entire discussion is the assumption that the axis of the molecule is hardly rotating during the collision. Dynamicists are very used to file idea that rotation of molecules is slow compared with the duration of a collision or a vibrational motion. That is correct, and is why experiments using selected reactants can demonstrate the reactive asymmetry between the two ends of a molecule. On the other hand, the intermolecular forces are not isotropic and can channel reactants preferentially into the cone of reaction or away from it. Only the detailed computations that we discuss in Chapter 5 can fully address such issues. 

The optically active a-sulfinyl vinylphosphonate 122 prepared in two different ways (Scheme 38) is an interesting reagent for asymmetric synthesis [80]. This substrate is an asymmetric dienophile and Michael acceptor [80a]. In the Diels-Alder reaction with cyclopentadiene leading to 123, the endo/exo selectivity and the asymmetry induced by the sulfinyl group have been examined in various experimental conditions. The influence of Lewis acid catalysts (which also increase the dienophilic reactivity) appears to be important. The 1,4-addition of ethanethiol gives 124 with a moderate diastereoselectivity. 

Both the alkyl and the acyl have two asymmetric centers the iron and the )3-carbon. Accordingly, each composition exists as a pair of racemic mixtures. When the two diastereomeric racemic mixtures of the acyl are separately subjected to the decarbonylation in Eq. (54), only partial (<50%) epimerization is observed by NMR spectroscopy. This indicates that in the reactive intermediate, presumably three-coordinate CpFe(PPh3)COCH2-CH(Me)Ph, the iron substantially retains its asymmetry, and is therefore not planar. 

Theoretical calculations have also permitted one to understand the simultaneous increase of reactivity and selectivity in Lewis acid catalyzed Diels-Alder reactions101-130. This has been traditionally interpreted by frontier orbital considerations through the destabilization of the dienophile s LUMO and the increase in the asymmetry of molecular orbital coefficients produced by the catalyst. Birney and Houk101 have correctly reproduced, at the RHF/3-21G level, the lowering of the energy barrier and the increase in the endo selectivity for the reaction between acrolein and butadiene catalyzed by BH3. They have shown that the catalytic effect leads to a more asynchronous mechanism, in which the transition state structure presents a large zwitterionic character. Similar results have been recently obtained, at several ab initio levels, for the reaction between sulfur dioxide and isoprene1. ... 

Ligand 73 was prepared directly from a single enantiomer of the corresponding naphthol of QUINAP 60, an early intermediate in the original synthesis, and both enantiomers of BINOL. Application in hydroboration found that, in practice, only one of the cationic rhodium complexes of the diastereomeric pair proved effective, (aA, A)-73. While (aA, A)-73 gave 68% ee for the hydroboration of styrene (70% yield), the diastereomer (aA, R)-73 afforded the product alcohol after oxidation with an attenuated 2% ee (55% yield) and the same trend was apparent in the hydroboration of electron-poor vinylarenes. Indeed, even with (aA, A)-73, the asymmetries induced were very modest (31-51% ee). The hydroboration pre-catalyst was examined in the presence of catecholborane 1 at low temperatures and binuclear reactive intermediates were identified. However, when similar experiments were conducted with QUINAP 60, no intermediates of the same structural type were found.100... 

Asymmetric diarylmethanes, hydrogenolytic behaviors, 29 229-270, 247-252 catalytic hydrogenolysis, 29 243-258 kinetics and scheme, 29 252-258 M0O3-AI2O3 catalyst, 29 259-269 relative reactivity, 29 255-257 schematic model, 29 254 Asymmetric hydrogenations, 42 490-491 Asymmetric synthesis, 25 82, 83 examples of, 25 82 Asymmetry factor, 42 123-124 Atom-by-species matrix, 32 302-303, 318-319 Atomic absorption, 27 317 Atomic catalytic activities of sites, 34 183 Atomic displacements, induced by adsorption, 21 212, 213 Atomic rate or reaction definition, 36 72-73 structure sensitivity and, 36 86-87 Atomic species, see also specific elements adsorbed... 

As discussed in this chapter, the fundamental host-guest chemistry of 1 has been elaborated to include both stoichiometric and catalytic reactions. The constrained interior and chirality of 1 allows for both size- and stereo-selectivity [31-35]. Additionally, 1 itself has been used as a catalyst for the sigmatropic rearrangement of enammonium cations [36,37] and the hydrolysis of acid-labile orthoformates and acetals [38,39]. Our approach to using 1 to mediate chemical reactivity has been twofold First, the chiral environment of 1 is explored as a source of asymmetry for encapsulated achiral catalysts. Second, the assembly itself is used to catalyze reactions that either require preorganization of the substrate or contain high energy intermediates or transition states that can be stabilized in 1. 

Some early kinetic studies on the enzymic reaction indicated that LADH exhibits pre-steady state half-of-the-sites reactivity. Bernard et al. reported that two distinct kinetic processes, well separated in rate, were observed for the conversion of reactants into products under conditions of excess enzyme.1367 They also reported that each of the two phases corresponded to conversion of exactly one half of the limiting concentration of substrate being converted to products. On the basis of this they proposed two possible models, the favoured one based on catalytically non-equivalent but interconvertible states of the two binding sites, with the possibility that the asymmetry of the sites may be induced by coenzyme binding. Further evidence for this non-equivalence of the subunits was obtained in similar subsequent studies using a chromophoric nitroso substrate, p-nitroso-A,JV-dimethylaniline with limiting NADH concentrations.1368... 

However, in their study of intermediates in the enzymic reduction of acetaldehyde, Shore and Gutfreund could find no inequivalence in the binding sites of the subunits at all NADH concentrations studied.1369 This conclusion that the two active sites are kinetically equivalent is supported by kinetic studies by Hadom et al.1370 and by Kvassman and Pettersson. 1 Work by Kordal and Parsons also supports this conclusion.13" They devised a method of persuading 3H-labelled NADH to bind to one site per enzyme molecule and then, using a stopped-flow technique, to react this with excess unlabelled product. Full site reactivity was observed in either direction. They concluded that no half site reactivity was observed, and that there was no indication of subunit asymmetry induced by either the coenzyme binding or by chemical reaction. 

A related phenomenon is half-of-the-sites or half-site reactivity, by which an enzyme containing 2n sites reacts (rapidly) at only n of them (Table 10.2). This can be detected only by pre-steady state kinetics. The tyrosyl-tRNA synthetase provides a good example, in that it forms 1 mol of enzyme-bound tyrosyl adenylate with a rate constant of 18 s1, but the second site reacts 104 times more slowly.13 However, as will be seen in Chapter 15, section J2b, protein engineering studies on the tyrosyl-tRNA synthetase unmasked a pre-existing asymmetry of the enzyme in solution. 

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