Base-Catalyzed Decarboxylation of Mandelylthiamin: Direct Formation of Bicarbonate as an Alternative to Formation of CO₂

Abstract

The decarboxylation of mandelylthiamin is subject to general base catalysis (β = 0.26), an outcome that is inconsistent with the expected dissociative transition state in which CO(2) forms along with a residual carbanion. The results implicate a previously unrecognized associative route in which addition of water to a carboxylate followed by base-catalyzed proton transfer and C-C cleavage produces bicarbonate directly. Various reports of the presence or absence of base catalysis in decarboxylation reactions are consistent with the associative route's occurrence in cases where nucleophiles would be generated along with CO(2) in the usual dissociative route.

Catalyzing decarboxylation by taming carbon dioxide

“…Further examination showed that the decarboxylation of MTh is subject to general base catalysis. The catalytic reaction has a relatively low β value (0.26), indicating that there is a real but small degree of proton transfer in the same step as C-C cleavage [11]. There is no mechanism that we could cite to explain these conclusions in terms of production of CO 2 from MTh in a single step.…”

“…Howe found that malonate monoanion is indeed a catalyst for the decarboxylation of MTh. However, when he tested the same reaction with acetic acid/acetate buffer, he saw acceleration as with malonate [11]. Further examination showed that the decarboxylation of MTh is subject to general base catalysis.…”

“…In a similar manner, enzymes that promote hydrolysis of proteins and nucleic acids overcome the kinetic barrier by providing pathways that do not exist in the normal milieu in which the compounds exist [10]. The possible similarity of the mechanisms for catalysis in hydrolytic and decarboxylation pathways has only recently begun to be recognized [11,12]. In this review our objective is to illustrate how decarboxylation is hindered by the nature of CO 2 and how that can be overcome by alternatives that achieve the same outcome in terms of the conversion of reactants to products by altering the nature of the precursor to CO 2 in the reaction mechanism.…”

“…We realized the possible existence of alternatives to CO 2 itself when we were confronted with observations that could not fit within mechanisms where CO 2 forms directly by cleavage of a C-C bond [11]. If direct formation of CO 2 in such a pathway is problematic, what is the nature of that problem and how can it be overcome by catalysis?…”

“…Upon C-C cleavage with transfer of a proton to the Brønsted base, bicarbonate rather than CO 2 is formed when the C-C bond breaks [11]. This would help overcome internal return as bicarbonate is polar and much more soluble than CO 2 [53], with those properties driving the reaction forward.…”