Catalytic bifurcation step

Adam and coworkers have characterized [Mn (salen)] complexes by ESI-MS/ MS [80]. The group proposed that cis and trans epoxide formation followed separate pathways, and the possibility that the reaction mixture had multiple, rapidly equilibrating oxidizing species, each of which preferentially followed one of the reaction pathways, could not be excluded. Herein, they suggested a bifurcation step in the catalytic cycle to account for the dependence of the diastereoselectivities on the oxygen source as depicted in Scheme 5.21 [80bj. 

The first step of the catalytic process is the hydrogen bond directed assembly and orientation of the reactants. In this example, the azlactone and methanol form a ternary starting complex with the organocatalyst (Fig. 1) [39]. The pseudo-Lewis acidic thiourea forms two bifurcated, nearly symmetric hydrogen bonds (2.147 A, < (0,H,N) = 155.5° and 2.146A, <(0,H,N) = 155.8°) to the carbonyl oxygen atom of the azlactone. 

A vital constituent of any chemical process that is going to show oscillations or other bifurcations is that of feedback . Some intermediate or product of the chemistry must be able to influence the rate of earlier steps. This may be a positive catalytic process , where the feedback species enhances the rate, or an inhibition through which the reaction is poisoned. This effect may be chemical, arising from the mechanistic involvement of species such as radicals, or thermal, arising because chemical heat released is not lost perfectly efficiently and the consequent temperature rise influences some reaction rate constants. The latter is relatively familiar most chemists are aware of the strong temperature dependence of rate constants through, e.g. the Arrhenius law,... 

Furthermore, reversibility of the early steps of the catalytic cycle implies that different pathways are converging in this system. Indeed, the solvate complex A can first react either with the substrate yielding B or with dihydrogen affording F. However, this is not a bifurcation point separating two different mechanisms. An addition of dihydrogen to B or of a substrate to molecule F would produce the common intermediate D that connects numerous interconverting intermediates of the two pathways... 

Practically it means that the whole network of possible catalytic pathways that may be converging and/or may contain bifurcation points must be computed before a reliable decision on the nature of the enantioselective step can be made. This, in turn, requires accurate knowledge of all possible experimenfal data on the relative stabilities of the intermediates, structure of fhe resting state, kinetics, etc., to calibrate and control the computational results. 

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