New Chiral Auxiliaries for Dynamic Kinetic Resolution: From Theory to Experiment

New efficient chiral auxiliaries for dynamic kinetic resolution (DKR) of bromides into amines are proposed, based on a theoretical rationalisation of known literature results. One example was synthesized and tested, affording diastereoselectivities up to 100 %. Several results of DKR reactions are known, based on oxazolidinone or imidazolidinone units as chiral auxiliaries. Nevertheless, their behaviour was not fully understood until a recent paper that we published. We now used our proposed mechanism to rationalize the behaviour of other similar chiral auxiliaries and to propose small structure changes in imidazolidinone rings which could largely improve their performance. We could show that the good performance of these molecules as chiral auxiliaries for DKR reactions where bromine is the leaving group and a primary or secondary amine is the nucleophile is due, in a first step, to the formation of a hydrogen bond between the amine and the ring carbonyl oxygen and, in a second step, to the strong electrostatic interaction between the leaving bromide and the carbonyl oxygen in the C‐3 substituent. Considering the behaviour of this substituent which rotates to minimize the electrostatic repulsion with the bromide when reaching the transition state, we proposed the introduction of a second substituent in the C‐4 position of the imidazolidinone ring, which prevents such rotation, thus increasing the energy difference between the transition states of the two distereoisomers. With such an auxiliary we were able to increase the best de known in literature (88 %), when benzylamine is used as nucleophile, to 99, or even 100 %, when iodide replaces the bromide in the substrate.     

New chiral auxiliaries for dynamic kinetic resolution: from theory to experiment

New efficient chiral auxiliaries for dynamic kinetic resolution (DKR) of bromides into amines are proposed, based on a theoretical rationalisation of known literature results. One example was synthesized and tested, affording diastereoselectivities up to 100%. Several results of DKR reactions are known, based on oxazolidinone or imidazolidinone units as chiral auxiliaries. Nevertheless, their behaviour was not fully understood until a recent paper that we published. We now used our proposed mechanism to rationalize the behaviour of other similar chiral auxiliaries and to propose small structure changes in imidazolidinone rings which could largely improve their performance. We could show that the good performance of these molecules as chiral auxiliaries for DKR reactions where bromine is the leaving group and a primary or secondary amine is the nucleophile is due, in a first step, to the formation of a hydrogen bond between the amine and the ring carbonyl oxygen and, in a second step, to the strong electrostatic interaction between the leaving bromide and the carbonyl oxygen in the C-3 substituent. Considering the behaviour of this substituent which rotates to minimize the electrostatic repulsion with the bromide when reaching the transition state, we proposed the introduction of a second substituent in the C-4 position of the imidazolidinone ring, which prevents such rotation, thus increasing the energy difference between the transition states of the two distereoisomers. With such an auxiliary we were able to increase the best de known in literature (88%), when benzylamine is used as nucleophile, to 99, or even 100%, when iodide replaces the bromide in the substrate.     

A Highly Stereoselective Chiral Auxiliary‐assisted Reductive Cyclization to Furoindoline

Highly stereoselective furoindoline derivatives were synthesized by exploring the imidazolidinone‐based chiral auxiliary‐mediated aldol adduct. The one‐pot reductive cyclization was achieved through NiCl₂.6H₂O/NaBH₄.     

A highly efficient stereoselective synthesis of β-lactams

An efficient strategy for a one-pot, single step synthesis of β-lactams employing an imidazolidinone based chiral auxiliary with various aldimines via asymmetric Mannich-type reaction has been described.     

Helical Poly(phenylacetylene) Bearing Chiral and Achiral Imidazolidinone‐Based Pendants that Catalyze Asymmetric Reactions due to Catalytically Active Achiral Pendants Assisted by Macromolecular Helicity

A series of optically active helical copolymers of phenylacetylenes are prepared by the rhodium‐catalyzed copolymerization of the imidazolidinone‐linked, catalytically active achiral phenylacetylenes and catalytically inactive chiral phenylacetylenes. The obtained chiral/achiral copolymers exhibit an induced circular dichroism in the UV–vis regions of the copolymer backbones resulting from a preferred‐handed helical conformation biased by the chiral imidazolidinone units incorporated in the copolymers. The copolymers are found to catalyze the asymmetric Diels–Alder reaction and produce the products with a moderate enantioselectivity in spite of the fact that the catalytically active units of the copolymers are achiral, indicating that the observed enantioselectivity totally originates from the helical chirality dynamically induced by the optically active, but catalytically inactive imidazolidinone units incorporated in the copolymers.

     

Chiral Dawson‐Type Hybrid Polyoxometalate Catalyzes Enantioselective Diels–Alder Reactions

Can achiral organocatalysts linked to chiral polyanionic metal oxide clusters provide good selectivity in enantioselective C?C bond formations? The answer to this question is investigated by developing a new active hybrid polyoxometalate‐based catalyst for asymmetric Diels–Alder reaction. Chirality transfer from the chiral anionic polyoxometalate to the covalently linked achiral imidazolidinone allows Diels–Alder cycloaddition products to be obtained with good yields and high enantioselectivities when using cyclopentadiene and acrylaldehydes as partners.     

有机催化不对称Michael加成反应

有机催化的不对称合成反应是目前研究最为活跃的领域之一. 不对称Michael加成反应是合成众多重要的手性合成子和药物中间体的有效手段. 目前报道的催化Michael加成反应的有机催化剂主要有脯氨酸及其衍生物、手性咪唑啉酮、手性(硫)脲、金鸡纳碱衍生物等. 对各类有机催化剂在有机催化不对称Michael加成反应中的应用, 以及不对称诱导反应的机理、催化剂分子结构及反应条件对其催化活性和不对称诱导作用的影响进行了评述.     

Enantioselective α-heterofunctionalisation of carbonyl compounds: organocatalysis is the simplest approach

Enantioselective organocatalytic processes have reached maturity in recent years with an impressive number of applications now available. The application of these advantageous methodologies to the construction of chiral α-hetereofunctionalised carbonyl compounds allows us to obtain important chiral building blocks, such as α-amino acids, α-amino alcohols, aziridines, epoxides, 1,2-diols and α-sulfenylated, selenenylated and halogenated carbonyl derivatives. Proline, imidazolidinone derivatives, cinchona alkaloids and their ammonium salts, as well as Brønsted acid derivatives, have been used as chiral catalysts for these purposes. A survey of contributions in this field will be discussed throughout this review.     

Organocatalytic Asymmetric Direct C sp 3H Functionalization of Ethers: A Highly Efficient Approach to Chiral Spiroethers

Spiro compounds: An organocatalytic asymmetric method for the C?sp?3?H functionalization of the α?position of racemic cyclic ethers has been developed. The transformation, mediated by catalytic amounts of an imidazolidinone and strong acid, involves a tandem 1,5-hydride transfer/cyclization and provides access to a structurally diverse series of chiral spiroethers with high levels of enantioselectivity.     

Stereoselectivity in metal carbene and Lewis acid-catalyzed reactions from diastereomeric dirhodium(II) carboxamidates: Menthyl N-acetyl-2-oxoimidazolidine-4(S)-carboxylates

The influence of a chiral menthyl group as the pendant ester substituent on the N-acetyl-2-oxoimidazolidine-4S-carboxylate ligands in chiral dirhodium(II) imidazolidinone catalysts has been examined. Significant match/mismatch influences are evident in the observed stereocontrol for carbon–hydrogen insertion reactions with diazoacetates, but these effects are minimal in cyclopropanation reactions. Steric restrictions prevent effective enantiocontrol in hetero-Diels–Alder reactions using these menthyl-substituted catalysts.     

含L-氨基酸基团的手性功能单体及与N-异丙基丙烯酰胺共聚物的合成

以L-苯丙氨酸（L-Phe）、L-色氨酸（L-Trp）和L-亮氨酸（L-Leu）3种常见的氨基酸为手性源,经过酯化、缩合等步骤制备3种手性功能单体AAc-L-Phe(AAc:丙烯酸)、AAc-L-Trp和AAc-L-Leu,其结构经过IR、1H NMR确证。 并将手性单体AAc-L-Phe与温敏材料N-异丙基丙烯酰胺(NIPAam)共聚,制备了手性共聚物P(NIPAam-co-AAc-L-Phe),结构经IR确证,示差扫描量热分析测试证明其具有温敏性。 这些手性功能单体有可能用于制备环境响应性手性高分子聚合物。     

Contribution of cation-π interactions in iminium catalysis

Ab initio calculations were carried out for a benzyl-substituted iminium cation derived from (E)-crotonaldehyde and a chiral imidazolidinone that was developed as an organocatalyst by MacMillan et al. At the MP2 level of theory it is predicted that the phenyl group is close to the iminium moiety in the most stable conformer, suggesting that the cation-π interaction contributes to the stabilization of this conformer. Energy decomposition analyses on model systems indicate that the electrostatic and polarization terms make significant contribution to the attractive interactions between the benzene ring and the iminium cation.     

Enantioselective organocatalytic Mukaiyama-Michael addition of silyl enol ethers to alpha,beta-unsaturated aldehydes

[reaction: see text] A highly enantioselective, organocatalytic Mukaiyama-Michael addition reaction of silyl ethers and alpha,beta-unsaturated aldehydes has been developed. The process, catalyzed by MacMillan's chiral imidazolidinone, affords delta-keto aldehydes in high yields (56-87%) and high enantioselectivities (85-97% ee). Moreover, the reaction is applicable to a wide range of silyl ethers and alpha,beta-unsaturated aldehydes and, as such, provides access to a range of important synthetic building blocks.     

手性配位聚合物的构筑及其应用

手性配位聚合物因其结构多样性、可调控性以及潜在的多功能性,已经成为当前化学和材料学的研究热点。在合成中,可以通过选择特定的非手性配体、手性配体、手性溶剂或手性模板剂等来构筑手性配位聚合物。此外,还可以选择特定的金属离子赋予目标手性配位聚合物光、电、磁、催化和非线性光学等性能。本文详细综述了近年来纯手性配位聚合物的合成方法,以及在手性分离、手性催化、非线性光学、铁电和多铁等领域的应用研究进展。最后,对手性配位聚合物的合成方法及应用前景进行了展望。     

Cyclotrimerization of diisocyanates toward high‐performance networked polymers with rigid isocyanurate structure: Combination of aromatic and aliphatic diisocyanates for tunable flexibility

A series of networked polymers bearing isocyanurate moiety was synthesized by cyclotrimerization of diisocyanates, with employing methylenediphenyl 4,4′‐diisocyanate and 1,6‐hexamethylenediisocyanate (HMDI) in several feed ratios. In spite of the large difference in intrinsic reactivity between these two diisocyanates, their coannulation proceeded efficiently by using sodium p‐toluenesulfinate (pTolSO₂Na) and 1,3‐dimethyl‐2‐imidazolidinone as a catalyst and a solvent, respectively. The resulting networked polymers were transparent and exhibited excellent thermal stability. In addition, HMDI‐rich feed ratios allowed for the formation of networked polymers with increased flexibility. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2631–2637     

Catalytic asymmetric α-alkylation of ketones and aldehydes with N-benzylic sulfonamides through carbon-nitrogen bond cleavage

A range of ketones and aldehydes smoothly undergo asymmetric S(N)1 α-alkylation with N-benzylic sulfonamides in the presence of 10 mol % of a chiral imidazolidinone and trifluoroacetic acid to give the corresponding products in good to excellent yields and with good enantioselectivity. This chemistry has been successfully extended to the asymmetric desymmetrization of 4-substituted cyclohexanones, which exhibits greater than 99:1 diastereoselectivity and good enantioselectivity.     

Recent developments in asymmetric catalysis using synthetic polymers with main chain chirality

Some recent developments in the use of main chain chiral polymer catalysts are summarized. These polymers are different from the traditional polymer catalysts that are prepared by anchoring monomeric chiral catalysts to an achiral polymer backbone. Three classes of synthetic main chain chiral polymers are discussed including: (1) helical polymers represented by polypeptides; (2) polymers with flexible chiral chains such as polyesters and polyamides; and (3) polymers of rigid and sterically regular chiral chains represented by chiral conjugated polybinaphthyls. Some of these polymer catalysts have shown high enantioselectivity in asymmetric organic transformations.     

Synthesis of chiral polymers containing thioetherified cinchonidinium repeating units and their application to asymmetric catalysis

A thiol-ene reaction of dithiol and two equivalents of cinchonidine afforded a thioetherified cinchonidine dimer. The dimer was treated with benzyl bromide to give a quaternary ammonium dimer. An ion exchange reaction of the cinchonidinium dimer and disodium disulfonate gave polymers containing chiral quaternary ammonium repeating units in their main-chain structures. Another type of chiral polymer was synthesized by quaternization polymerization. Repeated quaternization reactions between the thioetherified cinchonidine dimer and dihalides yielded chiral polymers containing cinchonidinium structures in their main chains. Both of these chiral polymers were successfully used as catalysts for the asymmetric alkylation of N-diphenylmethylene glycine tert-butyl ester. The chiral cinchonidinium polymers explored in this study showed excellent catalytic activity in asymmetric alkylation reactions and were reused several times without loss of activity.     

Synthesis of main-chain chiral quaternary ammonium polymers for asymmetric catalysis using quaternization polymerization

Main-chain chiral quaternary ammonium polymers were successfully synthesized by the quaternization polymerization of cinchonidine dimer with dihalides. The polymerization occurred smoothly under optimized conditions to give novel type of main-chain chiral quaternary ammonium polymers. The catalytic activity of the polymeric chiral organocatalysts was investigated on the asymmetric benzylation of N-(diphenylmethylidene)glycine tert-butyl ester.     

Highly Enantioselective Diels–Alder Reaction Catalyzed by Chiral Imidazolidinone

New chiral imidazolidinone with an indole group was synthesized and used to catalyze the Diels–Alder reaction of α,β-unsaturated aldehyde with diene. High enantiomeric excesses and good yields were obtained. The reaction media were also surveyed. The best result in terms of enantioselectivity was achieved using acrolein and 2,3-dimethylbutdiene (up to 95% ee) in CH₃OH/H₂O.