Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory

Abstract

The mechanism of the Soai reaction has been thoroughly investigated at the M05-2X/6-31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non-enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2-methylpyrimidine-5-carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.

Natural Abundance Isotopic Chirality in the Reagents of the Soai Reaction

“…N is not included in our analysis, even if a very recent study has shown that chirality caused (only) by N-isotopes can control the enantiomeric outcome of the Soai reaction [43]. Some fragments of hypothetic intermediates [44][45][46] of the Soai autocatalysis show chiral arrangement of the Zn atoms. One of these fragments, the structure of which has been essentially supported by X-ray crystallography [47], will also be included in the present study.…”

“…Reasonable theoretical efforts at the elucidation of the structure of the possible intermediates have been published on the basis of "first principles" and other calculations [44][45][46]49], as well as kinetic/calorimetric/spectroscopic measurements [51,52] (only to mention the most cited ones). Very recently, even realistically designed and prepared model compounds could be crystallized and studied by X-ray crystallography [47].…”

“…This is a fundamental difference, especially from the viewpoint that in 2 the i-Pr groups are present before the C-C bond making it an alkylation step, while the i-Pr group in 3 represent a final stage; that is, the stage when the fate of the asymmetry of the critical carbon atom has already been decided. On the other hand, compound 3 appears as autocatalyst in the subsequent cycle(s) of the reaction in intermediate(s), the structure of which is actually known only from theoretical studies [44][45][46][47]49] The analysis of the eventual role of isotopically chiral i-Pr group(s) will be deduced step-by-step starting with the methyl group.…”

“…It appeared therefore challenging to identify (eventual) structural features in the polymetallic intermediates hypothesized for the Soai reaction [44][45][46] where the chirality is caused by spatial distribution of Zn isotopes. The most striking structural element of this kind was found in the number 9 intermediate suggested by Schiaffino and Ercolani [44] (S-E9), as shown in Figure 3A.…”

Stochastic and empirical models of the absolute asymmetric synthesis by the Soai-autocatalysis

“…We supposed, the fact of exclusion of simple stochastic formalisms for the description of the absolute AAS variant of the Soai reaction might indicate a more complicated mechanism, which might be described by a more complex stochastic law. Interestingly, while we were working on the statistical approach from this point of view, Ercolani and Schiaffino [81][82][83][84][85], in a couple of excellent papers arrived qualitatively at the same conclusion, on a very different basis, by theoretical calculations, in an attempt at identifying possible intermediates of the Soai autocatalysis.…”