DOI: 10.1002/cctc.201402765 Recycling Powered by Release of Carbon Dioxide Anna Laurell Nash, Khalid Widyan, and Christina Moberg* [a] In a cyclic process, fed with external chemical energy generat- ed by the transformation of a compound with high chemical potential to carbon dioxide, the undesired enantiomer from a catalytic asymmetric reaction is continuously recycled to starting reagent. This minor enantiomer recycling is character- ized by gradually increasing yields and product enantiomeric ratios. The requirements for maintaining a cyclic procedure are discussed; the necessity of a coupled exergonic process is demonstrated experimentally. Recycling procedures have been invoked in several models for the emergence of homochirality in autocatalytic systems. [1–3] Whereas such procedures may be feasible in open systems, in- corporation of reverse reactions in models describing closed systems has been subject to intense discussions. [4] As pointed out already by Onsager, in a triangle reaction involving A, B, and C, at equilibrium each transformation is just as likely as its reverse, that is, transformation of A to B takes place as often as transformation of B to A (Scheme 1 a). [5] As each forward and backward reaction must balance, net cycling is not possible; a unidirectional cycle would necessarily involve a thermody- namically uphill process. Continuous addition of a reagent may serve to push the equilibrium for a forward reaction, and con- sequently for the entire cycle, but this shift does not help the reverse reaction to climb the high energy barrier. However, if a chemical process is performed in a system open to mass flow and coupled to a thermodynamically downhill reaction by transformation of a sacrificial reagent to a by-product with lower chemical potential, a cyclic process operating out of equilibrium may be maintained, [6] in analogy to the way cellu- lar work is powered by adenosine triphosphate through cou- pling of exergonic to endergonic reactions. Recycling of the undesired enantiomer to achiral starting material may also serve to improve the enantiomeric excess in catalytic reactions. Onsager’s example describes an isomeriza- tion process, but an analogous situation applies to a reaction network involving an enantioselective reaction with recycling of the minor enantiomer. If the forward, product-forming reac- tion favors formation of the R enantiomer, the principle of mi- croscopic reversibility states that the reverse reaction cannot favor the reaction of S. However, chemical energy input by influx of a sacrificial reagent (X) with high chemical energy and the removal of compounds (Y and/or Z) with lower energies may serve as the driving force for a cyclic process (Scheme 1 b). [6] For simplicity, it is assumed that the forward reaction of achiral reactant A with reagent X produces a racemic product, that is, k R = k S , in which k R and k S are the rate constants for for- mation of the R and S enantiomers, respectively, from A, and that the reverse reaction, which restores the starting reagent and produces by-products Y and Z, proceeds with high selec- tivity, such that k’ R  0, for which k’ R is the rate constant for de- composition of the R enantiomer. Under these assumptions, the processes are described by Equations (1)–(4), and the net reaction by Equation (5). The latter is composed of a selective forward reaction A + X !R accompanied by transformation of sacrificial reagent X to Y + Z. Provided this coupled transforma- tion is exergonic, a cyclic process may be realized. A þ X k R ! R ð1Þ A þ X k S ! S ð2Þ S k S 0 ! S 0 þ Y ð3Þ S 0 k A ! A þ Z ð4Þ __________________ A þ 2X ! R þ Y þ Z ð5Þ We have previously accomplished a cyclic process consisting of the acylcyanation of prochiral aldehydes [7] combined with enzymatic hydrolysis of the minor enantiomer to restore the starting aldehyde. [8] This process relied on the formation of acetate as the thermodynamic driving force and was character- ized by steadily increasing product yield and ee. We thought that evolution of CO 2 should serve as a viable alternative ther- modynamic driving force for a cyclic process, in analogy to the use of chemical energy to drive uphill processes in living sys- tems and the release of CO 2 as metabolic waste. Herein, we Scheme 1. a) Onsager’s triangle, in which A, B, and C represent isomers. b) Recycling of minor S enantiomer to starting reagent A via S’ by transfor- mation of sacrificial reagent X to low energy products Y and Z. [a] A. Laurell Nash, Dr. K. Widyan, + Prof. C. Moberg Department of Chemistry, Organic Chemistry KTH Royal Institute of Technology SE 10044 Stockholm (Sweden) E-mail : kimo@kth.se [ + ] Present address: Department of Chemistry Tafila Technical University, Tafila (Jordan) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cctc.201402765. # 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ChemCatChem 2014, 6, 3314 – 3317 3314 CHEMCATCHEM COMMUNICATIONS