Chiral Autoamplification Meets Dynamic Chirality Control to Suggest Nonautocatalytic Chemical Model of Prebiotic Chirality Amplification

Oxidative kinetic resolution of 1-phenylethanol in the presence of manganese complexes, bearing conformationally nonrigid achiral bis-amine-bis-pyridine ligands, in the absence of any exogenous chiral additives, is reported. The only driving force for the chiral discrimination is the small initial enantiomeric imbalance of the scalemic (nonracemic) substrate: the latter dynamically controls the chirality of the catalyst, serving itself as the chiral auxiliary. In effect, the ee of 1-phenylethanol increases monotonously over the reaction course. This dynamic control of catalyst chirality by the substrate has been unprecedented; a consistent kinetic model for this process is presented. The reported catalyzed substrate self-enantioenrichment mechanism is discussed in relation to the problem of prebiotic chirality amplification.

The mixture was stirred overnight at r. t., diluted with water (2 mL), and extracted with CH 2 Cl 2 (3×5 mL). Combined organic extracts were washed with aqueous NaCl, dried with CaSO 4 , and evaporated under reduced pressure. The crude product was purified on a short SiO 2 column (eluent: acetone; acetone:MeOH 5:1), to yield the desired product (173 mg, 70 %).

Kinetic resolution procedures
Kinetic resolution of scalemic 1-phenylethanol Scelemic 1-phenylethanol mixtures were prepared by mixing calculated volumes of racemic and non-racemic 1-phenylethanol (either homemade 92 % ee (S)-1-phenylethanol or commercial (R)-1- phenylethanol, >99.0 % ee, SigmaAldrich). The resulting mixture with total amount of 1phenylethanol of 0.18…0.23 mmol and of appropriate manganese complex (0.2 µmol) in CH 3 CN (0.40 mL; or 0.8 or 0.2 mL in the case of experiments presented in Figure 2, red, and green curves, respectively) was prepared and analyzed by chiral HPLC (twice) to obtain the initial enantiomeric imbalance (ee 0 ). The mixture was thermostated at -10 °C, and 30 % aqueous H 2 O 2 was added in appropriate portions (typically 2-5 µL every 0.5 h. At the end of each 0.5 h period, 2.5 µL aliquot was taken, dissolved in 0.25 mL of i-propanol, and analyzed by chiral HPLC to obtain the relative concentrations of the alcohol and the ketone, and the alcohol ee at several different conversions. The results were presented in the form of ee vs. conversion and [S]/[R] vs. conversion plots.

Kinetic resolution of scalemic alkyl mandelates
The solution of the appropriate racemic alkyl mandelate and enantiopure (R)-alkyl mandelate (total amount of alkyl mandelate 0.2 mmol) and of appropriate manganese complex (0.2 µmol) in CH 3 CN (0.40 mL) was prepared and analyzed by chiral HPLC (twice) to obtain the initial enantiomeric imbalance (ee 0 ). The mixture was thermostated at -10 °C, and 30 % aqueous H 2 O 2 was added in appropriate portions (typically 2-5 µL every 0.5 h. At the end of each 0.5 h period, 2.5 µL aliquot was taken, dissolved in 0.25 mL of i-propanol, and analyzed by chiral HPLC to obtain the relative concentrations of the alcohol and the ketone, and the alcohol ee at several different conversions. No increase in the ee was observed over the reaction course.
Assuming that the enantiomerization equilibrium of the free catalyst is the fastest reaction in We notice the following self-evident relationships: which in combination with eq. (S1), (S2) and (S3) leads to the following equation Taking into account that, evidently, k S R = k R S and k S S = k R R , multiplying left and right parts of (S6) by R 0 /S 0 (R 0 and S 0 are the initial concentrations of the ( Parameters A and B can be revealed by fitting the ee vs. conversion or, better, er vs. conversion dependencies to the experimental points. For this purpose, the following obvious relationships have been used:     The corresponding ee vs. conversion and er vs. conversion curves are presented in Figure S2.   Figure S4. Enantiomeric excess (ee) vs. conversion plots for the kinetic resolution of -(S)-1-phenylethanol in the presence of achiral catalyst 1 (wine, ee 0 = 15.7%; entry 3 of Table 1); -(S)-1-phenylethanol in the presence of achiral catalyst 2 (blue, ee 0 = 19.4%; entry 6 of Table 1); -(S)-1-phenylethanol in the presence of achiral catalyst 3 (orange, ee 0 = 12.8%; entry 7 of Table 1); -(R)-methyl mandelate in the presence of achiral catalyst 1 (red, ee 0 = 17.4%; entry 8 of Table 1).
S--+ X-ray crystallography X-ray data for complex 1 and 3 Single-crystal diffraction data for 1 and 3 were collected at room temperature on a Bruker Kappa Apex II CCD diffractometer using φ, ω scans of narrow (0.5°) frames with Mo Kα radiation (λ = 0.71073 Å) and a graphite monochromator. The structures were solved by direct methods and refined by full-matrix least-squares method against all F 2 in anisotropic (isotropic for H) approximation using the SHELX-97 programs set. S1 Absorption corrections were applied based on intensities of equivalent reflections using SADABS programs. S2 The hydrogen atoms positions were calculated geometrically and refined in riding model exept the water hydrogens refined independently with restriction of O-H bond length of 0.83 Å. Free solvent accessible volume for compound 2 derived from PLATON S3,S4 routine analysis was found to be 11.6% (449.8 Å 3 ). This volume is occupied by highly disordered solvent molecules that could not be modeled as a set of discrete atomic sites. We employed PLATON/SQUEEZE procedure to calculate the contribution to the diffraction from the solvent region and thereby produced a set of solvent-free diffraction intensities. The most probable solvents can be H 2 O and/or acetonitryl. Asymmetric unit of 5 contains two independent molecules.
The crystallographic data and details of the structure refinements are summarized in Table   S4. Selected bond distances and angles are listed in Table S5 for 1 and Table S6 for 3.
In contrast to previously reported bipyrrolidine-and 1,2-ethylenediamine derived aminopyridine Mn triflates, in 1 and 3, only one of the triflates is coordinated to Mn, while the other Mn cite is occupied by H 2 O molecule ( Figure S7). In both complexes, hydrogens of the Mncoordinated water molecules form О-Н···О hydrogen bonds with the outer-sphere triflates, forming associates (supermolecules) consisting of two Mn complexes and two triflate molecules ( Figure S8).
Geometry optimizations were carried out without symmetry restrictions. Solvation effects (with CH 3 CN or H 2 O) were incorporated using polarized continuum model (PCM) method as implemented in GAUSSIAN 09. The results are presented in Table S8 and Figure S9. Notice: Artifacts, originating from the eluent "front" are observed at 3-5 min: they were not integrated.