Fluorous biphasic hydrolytic kinetic resolution of terminal epoxides

Although application of light-fluorous techniques facilitates the isolation of reaction products from the hydrolytic kinetic resolution (HKR) of terminal epoxides catalysed by cobalt complexes of salen ligands, the extension of the original fluorous biphasic approach to this reaction is far from being a trivial exercise. The nature of the counter anion has a dramatic effect on the catalytic activity of heavily fluorinated chiral (salen) cobalt(III) complexes. Excellent enantioselectivities are obtained in the fluorous biphasic HKR of 1,2-hexene oxide when fluorinated anions are introduced (e.e.s up to 99% both for the diol and the epoxide), with C₈F₁₇COO^- affording reaction rates even higher than those observed with non-fluorous systems.     

Mechanistic investigation leads to a synthetic improvement in the hydrolytic kinetic resolution of terminal epoxides

The mechanism of the hydrolytic kinetic resolution (HKR) of terminal epoxides was investigated by kinetic analysis using reaction calorimetry. The chiral (salen)Co-X complex (X = OAc, OTs, Cl) undergoes irreversible conversion to (salen)Co-OH during the course of the HKR and thus serves as both precatalyst and cocatalyst in a cooperative bimetallic catalytic mechanism. This insight led to the identification of more active catalysts for the HKR of synthetically useful terminal epoxides.     

Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)Co(III) complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols

The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral (salen)Co(III) complex 1 x OAc affords both recovered unreacted epoxide and 1,2-diol product in highly enantioenriched form. As such, the HKR provides general access to useful, highly enantioenriched chiral building blocks that are otherwise difficult to access, from inexpensive racemic materials. The reaction has several appealing features from a practical standpoint, including the use of H(2)O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable, commercially available catalyst. In addition, the HKR displays extraordinary scope, as a wide assortment of sterically and electronically varied epoxides can be resolved to > or = 99% ee. The corresponding 1,2-diols were produced in good-to-high enantiomeric excess using 0.45 equiv of H(2)O. Useful and general protocols are provided for the isolation of highly enantioenriched epoxides and diols, as well as for catalyst recovery and recycling. Selectivity factors (k(rel)) were determined for the HKR reactions by measuring the product ee at ca. 20% conversion. In nearly all cases, k(rel) values for the HKR exceed 50, and in several cases are well in excess of 200.     

Chiral Co(III)(salen)-catalysed hydrolytic kinetic resolution of racemic epoxides in ionic liquids

In the chiral Co(III)(salen)-catalysed HKR of racemic epoxides, in the presence of ionic liquids, Co(II)(salen) complex is oxidised without acetic acid to catalytically active Co(III)(salen) complex during reaction and, moreover, this oxidation state is stabilised against reduction to Co(II) complex which enables the reuse of the recovered catalyst for consecutive reactions without extra reoxidation.     

Self-assembly approach toward chiral bimetallic catalysts: bis-urea-functionalized (salen)cobalt complexes for the hydrolytic kinetic resolution of epoxides

A series of novel bis-urea-functionalized (salen)Co complexes has been developed. The complexes were designed to form self-assembled structures in solution through intermolecular urea-urea hydrogen-bonding interactions. These bis-urea (salen)Co catalysts resulted in rate acceleration (up to 13 times) in the hydrolytic kinetic resolution (HKR) of rac-epichlorohydrin in THF by facilitating cooperative activation, compared to the monomeric catalyst. In addition, one of the bis-urea (salen)Co(III) catalyst efficiently resolves various terminal epoxides even under solvent-free conditions by requiring much shorter reaction time at low catalyst loading (0.03-0.05 mol %). A series of kinetic/mechanistic studies demonstrated that the self-association of two (salen)Co units through urea-urea hydrogen bonds was responsible for the observed rate acceleration. The self-assembly study with the bis-urea (salen)Co by FTIR spectroscopy and with the corresponding (salen)Ni complex by (1)H NMR spectroscopy showed that intermolecular hydrogen-bonding interactions exist between the bis-urea scaffolds in THF. This result demonstrates that self-assembly approach by using non-covalent interactions can be an alternative and useful strategy toward the efficient HKR catalysis.     

New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions

The solvent-free hydrolytic kinetic resolution of terminal epoxides catalyzed by a new oligomeric (salen)Co complex 2 is described. Extremely low loadings of catalyst were used to provide all epoxides examined in good yields and >99% ee under ambient conditions within 24 h.     

Chiral cobalt salen complexes containing Lewis acid: A highly reactive and enantioselective catalyst for the hydrolytic kinetic resolution of terminal epoxides

A type of chiral salen complexes bearing Lewis acid, including FeCl₃, AlCl₃, ZnCl₂, and SnCl₄ has been synthesized. The prepared complexes proved to be reactive and enantioselective in the hydrolytic kinetic resolution of terminal epoxides. The catalysts could be recovered and reused several times with simple treatment after reaction, without loss of activity and enantioselectivity. (salen)Co(II) and Lewis acid in mol ratios of 1: 1, 1: 2, and 1: 3 showed the same activity, enatioselectivity, and stability. The characterization of the complexes in-situ generated by the reaction of (salen)Co(II) and Lewis acid in mol ratios of 1: 1, 1: 2, and 1: 3 in CH₂Cl₂ was performed by UV-Vis, which showed an identical spectrum and did not display any change along with the time prolonged. Thus, the present catalysts can be applicable for large scale processes for HKR reaction of racemic epoxides.     

Asymmetric ring opening of terminal epoxides via kinetic resolution catalyzed by chiral (salen)Co mixture

The highly enantioselective hydrolytic kinetic resolution (HKR) of racemic terminal epoxides by bimetallic chiral (salen)Co and (salen)Co(III)-OAc mixture provides a simple and effective method for the synthesis of enantiomerically enriched terminal epoxides (ee > 99%) and diols. At the equimolar amounts of bimetallic chiral (salen)Co and (salen)Co(II)-OAc, the catalytic activity increases more than two times in comparison with (salen)Co(III)-OAc used alone. The mixed catalytic system can be recycled and reused. No significant loss of catalytic activity was observed after three runs.     

Chiral nanoporous metal-metallosalen frameworks for hydrolytic kinetic resolution of epoxides

Chiral nanoporous metal-organic frameworks are constructed by using dicarboxyl-functionalized chiral Ni(salen) and Co(salen) ligands. The Co(salen)-based framework is shown to be an efficient and recyclable heterogeneous catalyst for hydrolytic kinetic resolution (HKR) of racemic epoxides with up to 99.5% ee. The MOF structure brings Co(salen) units into a highly dense arrangement and close proximity that enhances bimetallic cooperative interactions, leading to improved catalytic activity and enantioselectivity in HKR compared with its homogeneous analogues, especially at low catalyst/substrate ratios.     

不具C2对称轴的Co（Ⅲ）（Salen)催化的末端环氧化合物的水解拆分

用（S）-3-甲基-1，2-丁二胺或（R）-1，2-丙二胺为原料与2-羟基-5-甲-3- 叔丁基苯甲醛缩合，得到不具C2对称轴的手性Salen, 与Co(Ⅱ）络各并氧化后得到 4a或4b.4a和4b成功地应用于外消旋末端环氧化合物的水解拆分，取得了较好的产 率，但产物的对映体过量值较低。     

Shell cross-linked micelle-based nanoreactors for the substrate-selective hydrolytic kinetic resolution of epoxides

Shell cross-linked micelles (SCMs) containing Co(III)-salen cores were prepared from amphiphilic poly(2-oxazoline) triblock copolymers. The catalytic activity of these nanoreactors for the hydrolytic kinetic resolution of various terminal epoxides was investigated. The SCM catalysts showed high catalytic efficiency and, more significantly, substrate selectivity based on the hydrophobic nature of the epoxide. Moreover, because of the nanoscale particle size and the high stability, the catalyst could be recovered easily by ultrafiltration and reused with high activity for eight cycles.     

The influence of solvent choice,acid activation and surfactant addition on the hydrolytic kinetic resolution (HKR) of terminal epoxides

The recently developed hydrolytic kinetic resolution (HKR) of epoxides catalysed by the Co-Jacobsen catalyst, is one of the most useful methods to obtain enantiomerically pure epoxides and/or diols. Several parameters can significantly influence the homogeneous reaction. Several factors including the used solvent, the activation of the catalyst and the use of surfactants, are investigated.     

Enantioselective aminolytic kinetic resolution (AKR) of epoxides catalyzed by recyclable polymeric Cr(III) salen complexes

Polymeric chiral Cr(III) salen complexes catalyzed regio-, diastereo-, and enantioselective aminolytic kinetic resolution (AKR) of trans-stilbene oxide, trans-β-methyl styrene oxide, and 6-CN-chromene oxide proceeded smoothly at room temperature, providing the desired anti-β-amino alcohols in high yields and enantiomeric excess (up to 100%).     

The use of solvent resistant nanofiltration in the recycling of the Co-Jacobsen catalyst in the hydrolytic kinetic resolution (HKR) of epoxides

The use of solvent resistant nanofiltration (SRNF) provides an elegant alternative to the classical heterogenization of homogeneous catalysts. The SRNF-membrane separates the catalyst from the reaction mixture and allows products and solvent to permeate. This concept is now applied to the Co-Jacobsen catalyst in the hydrolytic kinetic resolution (HKR) of epoxides. A range of commercially available NF-membranes and three laboratory prepared membranes were subjected to filtration tests in diethylether, isopropanol and under solvent-free conditions. The membranes with the best performance were selected to recycle the Co-Jacobsen catalyst under catalytic conditions. Finally, the membrane reactor developed for the IPA-system, was optimized through the screening of different process parameters, including temperature, pressure and membrane thickness.     

New chiral cobalt salen complexes containing Lewis acid BF3; a highly reactive and enantioselective catalyst for the hydrolytic kinetic resolution of epoxides

A new type of chiral cobalt salen complexes bearing BF₃ Lewis acid proved to be reactive and enantioselective in the hydrolytic resolution of terminal epoxides. The polymer type salen catalysts also showed a high enantioselectivity in the same reaction.     

Highly reactive and enantioselective kinetic resolution of terminal epoxides with H2O and HCl catalyzed by new chiral (salen)Co complex linked with Al

The asymmetric hydrolytic kinetic resolution (HKR) of racemic terminal epoxides by new easily synthesized dimeric chiral (salen)Co bearing Al, provides a practical and straightforward method for the synthesis of enantiomerically enriched terminal epoxides (>99% ee) and diols. An inorganic acid, HCl is applied first time for the asymmetric ring opening reaction of terminal epoxides. Reactions are conveniently carried out at room temperature under an air atmosphere.     

Asymmetric synthesis of (S)-vigabatrin and (S)-dihydrokavain via cobalt catalyzed hydrolytic kinetic resolution of epoxides

A concise route to the asymmetric synthesis of (S)-vigabatrin^® and (S)-dihydrokavain has been described using Co-catalyzed hydrolytic kinetic resolution of racemic epoxides and regiospecific opening of terminal epoxides with dimethylsulfonium methylide as the key steps.