Asymmetric Synthesis of Indoline from Achiral Phthalimide Involving Crystallization-Induced Deracemization

Asymmetric synthesis was performed by combining the photochemical reaction of an achiral substrate followed by crystallization-induced deracemization. The results indicated that a fused indoline produced by photochemical intramolecular δ-hydrogen abstraction and cyclization of N-(5-chloro-2-methylphenyl)phthalimide crystallized as a racemic conglomerate. Since this substrate has an aminal skeleton, racemization involving a ring-opening and ring-closing equilibrium process occurred under suitable conditions. Efficient racemization was observed in acetone containing a catalytic base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Crystallization-induced dynamic deracemization by Viedma ripening from racemic indoline was performed with an excellent enantioselectivity of 99 % ee. Furthermore, one-pot asymmetric synthesis of the indoline was achieved by the photochemical reaction of achiral phthalimide followed by continuous attrition-enhanced deracemization converging to 99 % ee of enantiomeric crystals. This is the first example of asymmetric expression and amplification by photochemical hydrogen abstraction and crystallization-induced dynamic deracemization.     

过渡金属配合物在不对称合成中的催化应用

综述了过渡金属配合物在不对称氢化、不对称环丙烷化、不对称环氧化等不对称合成中的催化应用以及最新的进展。参考文献35篇。     

Absolute Asymmetric Synthesis of Enantiopure Organozinc Reagents,Followed by Highly Enantioselective Chlorination

We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by using total spontaneous resolution followed by enantiospecific conversion into 1‐chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp=2,6‐dichlorophenoxy and tmeda=N,N,N′,N′‐tetramethylethylenediamine) ( 3 ) was prepared from the achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6‐dichlorophenol. The reagent resolved spontaneously on crystallization, and single crystals of 3 react with N‐chlorosuccinimide in the presence of benzoquinone in 2‐propanol to give 1‐chloroindene in >98 % enantiomeric excess. It was found that (R)‐ 3 gave (R)‐1‐chloroindene upon reaction, indicating an S_E2′‐mechanism. Since bulk samples of 3 gave optically active product upon chlorination, total spontaneous resolution must have occurred. This demonstrates that enantiopure products can be obtained through the absolute asymmetric synthesis of organometallic reagents starting from achiral materials. The general absolute asymmetric synthesis (AAS) method offers easy access to both enantiomers and an almost limitless variation in the design of the product.     

Absolute Asymmetric Synthesis in Enantioselective Autocatalytic Reaction Networks: Theoretical Games,Speculations on Chemical Evolution and Perhaps a Synthetic Option

The Soai reaction and the Viedma deracemization of racemic conglomerate crystal mixtures are experimental pieces of evidence of the ability of enantioselective autocatalytic coupled networks to yield absolute asymmetric synthesis. Thermodynamically open systems or systems with non‐uniform energy distributions may lead to chiral final states and, in systems able to come into thermodynamic equilibrium with their surroundings, to kinetically controlled absolute asymmetric synthesis. The understanding of network parameters and of the thermodynamic scenarios that may lead to spontaneous mirror symmetry breaking (SMSB) could assist in the development of new methods for asymmetric synthesis and enantioselective polymerizations (e.g., replicators), and to frame reasonable speculations on the origin of biological homochirality.     

Asymmetric Inducing Synthesis of Optically Active Tetrahedral Cluster Containing SMCoW Core

The chiral clusters (μ3-S)MCoW(CO)8[η^5-C5H4C(O)OCH3] [M=Ru(2), Fe(3)] were synthesized by asymmetric induction of N-benzylcinchonium chloride as phase-transfer catalyst (PTC). The most suitable amount of PTC is 70 mol%. Cluster 3 was determined by single crystal X-ray diffraction analysis. The best ee of the chiral cluster is over 20%.     

Absolute Asymmetric Synthesis: Protected Substrate Oxidation

Three new conglomerates incorporating bidentate sulfide ligands coordinated by Ru^II centers have been prepared. Total spontaneous resolution by slow crystallization gives highly enantioenriched crystal batches, which are used in enantioselective oxidation of the sulfide ligands to give chiral sulfoxide complexes with >98 % ee. All relevant stereoisomers have been characterized by single‐crystal X‐ray diffraction, CD spectroscopy, and chiral HPLC. If the ligand range can be extended to monodentate sulfides, a large‐scale and recyclable process for enantioselective oxidation of sulfides can be designed.     

Photoracemization-Based Viedma Ripening of a BINOL Derivative

Viedma ripening is a deracemization process that has been used to deracemize a range of chiral molecules. The method has two major requirements: the compound needs to crystallize as a conglomerate and it needs to be racemizable under the crystallization conditions. Although conglomerate formation can be induced in different ways, the number of racemization methods is still rather limited. To extend the scope of Viedma ripening, in the present research we applied UV-light-induced racemization in a Viedma ripening process, and report the successful deracemization of a BINOL derivative crystallizing as a conglomerate. Irradiation by UV light activates the target compound in combination with an organic base, required to promote the excited-state proton transfer (ESPT), leading thereafter to racemization. This offers a new tool towards the development of Viedma ripening processes, by using a cheap and “green” catalytic source like UV light to racemize suitable chiral compounds.     

Organocatalytic Asymmetric Synthesis of an Advanced Intermediate of (+)-Sarain A

The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)-sarain A.     

Chiral Auxiliaries as Emerging Tools for the Asymmetric Synthesis of Octahedral Metal Complexes

New methods for the stereocontrolled synthesis of octahedral metal complexes are needed in order to fully exploit the stereochemical richness of the octahedron in the fields of catalysis, materials sciences, and life sciences. Whereas a large body of work exists regarding the diastereoselective coordination chemistry with chiral ligands, such efforts are restricted to certain carefully designed chiral ligands which remain in the coordination sphere. The emerging strategy of chiral‐auxiliary‐mediated asymmetric synthesis holds promise to solve the problem of controlling relative and absolute configuration in octahedral metal complexes in a general fashion, thus hopefully in the future providing access to any desired optical active octahedral metal complex without the need for chiral separations. This short review will summarize reported examples of chiral auxiliaries applied to the asymmetric synthesis of octahedral metal complexes.     

过渡金属催化不对称C-H键官能团化反应构建轴手性联芳基化合物研究进展

在手性分子中,轴手性化合物占据着非常重要的地位.从原子和步骤经济性方面考虑,利用不对称碳-氢官能团化反应构建轴手性化合物是最简洁高效的方法.随着过渡金属催化的不对称碳-氢键官能团化领域的逐步发展,利用该策略来构建轴手性联芳基化合物的研究成果也不断涌现.本文综述了通过过渡金属钯、铑和铱催化的不对称碳-氢键官能团化反应合成轴手性联芳基化合物的最新进展.此外,还介绍了利用这些方法合成多种轴手性配体及其催化的不对称反应,以及这些方法在天然产物合成中的应用.     

Asymmetric Synthesis of Biaryl Atropisomers Using an Organocatalyst-Mediated Domino Reaction as the Key Step

A three-pot synthetic method that features the use of an organocatalyst as the key step was developed for the preparation of biaryl atropisomers. The first reaction is an asymmetric domino Michael–Henry reaction catalyzed by diphenylprolinol silyl ether to afford the substituted nitrocyclohexanecarbaldehyde with four stereogenic centers and one defined configuration of a stereogenic axis with excellent enantioselectivity. Removal of the central chirality from the domino products afforded biaryl atropisomers having axial chirality with excellent enantioselectivity.     

手性双核催化剂在不对称合成中的应用研究进展

综述了含相同金属的手性双核铑配合物、手性以核钯配合物、手性双核钛配合 物、手性双核铜配合物等催化体系在烯烃的环丙烷化、亚胺的烯丙基化、氰硅化、 缩合等不对称合成中的应用。     

A Different Approach to Enantioselective Organic Synthesis: Absolute Asymmetric Synthesis of Organometallic Reagents

Voilà, optical activity : Both enantiomers of 1‐chloroindene have been synthesized in high selectivity from solely achiral starting materials, and without using optically active catalysts (see scheme). These symmetry‐breaking syntheses provide a proof‐of‐concept for a new approach to asymmetric synthesis. NCS=N‐chlorosuccinimide.