Structurally well-defined, recoverable C3-symmetric tris(beta-hydroxy phosphoramide)-catalyzed enantioselective borane reduction of ketones

[reaction: see text] A series of new chiral C(3)-symmetric tris(beta-hydroxy phosphoramide) ligands have been synthesized via the reaction of trisphosphoramide ester and Grignard reagents. The catalytic asymmetric borane reduction of ketones with these new C(3)-symmetric chiral tris(beta-hydroxy phosphoramide)s was investigated. Structurally well-defined, recoverable ligand 1d is an efficient catalyst for the enantioselective borane reduction of both electron-deficient and electron-rich ketones, and high enantioselectivities were achieved (up to 98% ee).     

The first immobilization of pyridine-bis(oxazoline) chiral ligands

[formula: see text] A chiral pyridine-bis(oxazoline) ligand, functionalized with a vinyl group in the pyridine ring, can be polymerized with styrene and divinylbenzene to obtain supported chiral ligands. As proof of the usefulness of this supported ligands, the corresponding ruthenium complexes are catalysts for the cyclopropanation reaction of styrene with ethyl diazoacetate with up to 85% ee.     

Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation

A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]     

Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition

The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides has been achieved. These new chiral diphosphine ligands could be employed as a ligand for the rhodium-catalyzed asymmetric catalyses.     

从碳中心到硅中心:手性螺环双膦配体研究的发展

手性螺环配体和催化剂已被公认是一类优势手性配体和催化剂。手性螺环配体的相关研究，促进了不对称催化领域的发展。根据螺环骨架类型进行分类，分别讨论具有螺[4.4]壬烷骨架、螺二氢茚骨架、螺[4.4]壬二烯骨架以及螺二色烷骨架的手性螺环双膦配体的合成及在不对称催化反应中的应用，为今后发展新的不对称催化体系提供了重要参考。     

Probing electronic effects in the asymmetric Heck reaction with the BIPI ligands

[structure: see text] The new BIPI ligands are phosphinoimidazolines that can be electronically tuned in three different ligand regions to explore electronic effects in asymmetric catalysis. Their application to the asymmetric Heck reaction (AHR) in the creation of a chiral quaternary center is described. Enantioselectivity is shown for the first time to depend linearly on phosphine electron density. Changing the ligand basicity by variation of the R(2) or R(3) substituents reverses facial selectivity.     

A new type of C2-symmetric bisphospine ligands with a cyclobutane backbone: practical synthesis and application

[reaction: see text] A highly efficient and practical optical resolution of anti-head-to-head racemic coumarin dimer, (+/-)-5, by molecular complexation with TADDOL (6) through hydrogen bonding and a convenient transformation of enantiopure 5 to a new type of C(2)-symmetric bisphosphine ligand (3) have been achieved. The asymmetric induction efficiency of these chiral bisphosphine ligands was evaluated in Pd-catalyzed asymmetric allylic substitution, affording the allylic substitution products in excellent yield (up to 99%) and enantioselectivity (up to 98.9% ee).     

Highly enantioselective michael additions of indole to benzylidene malonate using simple bis(oxazoline) ligands: importance of metal/ligand ratio

[Structure: see text] Simple bis(oxazoline) ligands, especially azabis(oxazolines), can catalyze the copper-catalyzed addition of indoles to benzylidene malonates in up to >99% ee, provided that excess of chiral ligand is avoided. The paradigm followed in many asymmetric catalyses that an excess of chiral ligand with respect to the metal should improve enantioselectivity because a background reaction by free metal is suppressed, is not applicable here, which might call for revisiting some of the many copper(II)-bis(oxazoline)-catalyzed processes known.     

A flexible and versatile strategy for the covalent immobilization of chiral catalysts based on pyridinebis(oxazoline) ligands

[reaction: see text] Flexible and versatile methods have been developed for the immobilization of chiral pyridinebis(oxazoline) ligands by covalent bonding to a solid support, either by grafting or by polymerization. Different spacers can easily be introduced to modulate the support-ligand distance and the electronic properties of the chiral ligand. As an example, 2,6-bis[(S)-4-isopropyloxazolin-2-yl]pyridine has been immobilized on polystyrene resins, both on a Merrifield-type resin by grafting and on supports prepared by polymerization of 4-vinyl-substituted ligands. The corresponding Ru complexes have been tested as catalysts in the cyclopropanation reaction between styrene and ethyl diazoacetate. The catalytic activity, the enantioselectivity, and the recyclability are strongly dependent on the catalyst preparation method and the total exclusion of oxygen and moisture in the filtration process. Under such optimized conditions, yields over 60% with up to 90% ee can be obtained in four successive reactions-the best cyclopropanation results described to date for a chiral solid ruthenium catalyst.     

New chiral P-N ligands for the regio- and stereoselective Pd-catalyzed dimerization of styrene

Two new chiral, enantiomerically pure, hybrid P-N ligands, namely (2R,5S)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octan-4-one (1) and (2R,5S)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octane (2), have been synthesized starting from L-proline. The two ligands differ in the presence or not of a carbonyl group in the diazaphosphane ring. Their coordination chemistry towards Pd(II) was studied by reacting them with [Pd(CH?)Cl(cod)]. A different behaviour was observed: ligand 2 shows the expected bidentate chelating behaviour leading to the mononuclear Pd-complex, while ligand 1 acts as a terdentate ligand giving a dinuclear species. The corresponding cationic derivatives were obtained from the palladium neutral complexes, both as mono- and dinuclear derivatives, and tested as precatalysts for styrene dimerization, yielding E-1,3-diphenyl-1-butene regio- and stereoselectively as the sole product. A detailed analysis of the catalytic behaviour is reported.     

Preparation of pyrrolidine-oxazoline containing ligands and their application in asymmetric transfer hydrogenation

Nine members of a new ligand class incorporating both an oxazoline ring and a pyrrolidine unit were prepared in an efficient four-step synthesis starting from readily available chiral amino alcohols and proline. A study of these ligands in the asymmetric transfer hydrogenation of acetophenone showed that the catalysts formed from [Ir(cod)Cl]₂ were the most active while those derived from [Ru(p-cymene)Cl₂]₂ gave the highest enantioselectivities (up to 61% ee).     

Synthesis of new chiral monodentate phosphite ligands and their use in catalytic asymmetric hydrogenation

[reaction: see text] New monodentate phosphite ligands have been developed from axially chiral biphenols, which show excellent enantioselectivity in the Rh(I)-catalyzed hydrogenation of dimethyl itaconate. The new chiral ligand system is suitable to create libraries and possesses fine-tuning capability.     

新轴手性N,N-Dioxide Biscarbolin衍生物催化酮亚胺的不对称硅氢化反应

以L-色氨酸为原料合成了5个伯酰胺结构的轴手性双咔啉N—O催化剂N2,N2'-二氧-9,9'-二甲基-3,3'-取代甲酰胺-β-双咔啉(4A~4E),并用于不对称催化酮亚胺的还原反应.结果表明,催化剂的催化转化率较高(80%~98%),立体选择性(e.e.值)较好,其中催化剂N2,N2'-二氧-9,9'-二甲基-3,3'-环己基甲酰胺-β-双咔啉(4B)的催化转化率达到了98%,e.e.值达68%.     

Highly Enantioselective Phenylacetylene Addition to Benzaldehyde Catalyzed by Chiral Tridentate Ligand

Development of new or improved methods for the asymmetric preparation of chiral propargylic alcohols has gained considerable significance during the past years because they are useful building blocks for the synthesis of many biologically active compounds and natural products.[1] A series of chiral tridentate ligands were conveniently synthesized from amino acids with good yields (Scheme 1).[2] A preliminary study of the enantioselective alkynylation of benzaldehyde catalyzed by this chiral tridentate ligand was carried out and up to 83% ee of chiral propargyl alcohols was obtained (Table 1 ). A further investigation of the tridentate ligand is currently underway.     

Synthesis and Catalytic Asymmetric Reaction of Chiral Pyridine Prolinol Derivatives

The enantioselective reduction of prochiral ketones with borane in the presence of a chiral ligand leading to enantiomerically pure secondary alcohols has received considerable attention in recent years. [1] Enantiomerically pure secondary alcohols are important intermediates for the synthesis of various other organic compounds such as halides, esters, ethers, ketones and amines. To the best of our knowledge, the use of pyridine prolinol derivatives in the reduction of ketones has not been reported so far. Thus, it should be of interest to investigate the catalytic a bility of such ligands. We have an ongoing project in the synthesis and application of chiral pyridine derivatives in chiral molecular recognition[2] and we want to evaluate the effect resulting from the introduction of a pyridinyl moiety onto the catalysts. We expect that the cooperation of pyridine unit and chiral prolinol unit in new ligands may result in unique properties for catalytic reaction.     

Enantioselective synthesis of P-stereogenic benzophospholanes via palladium-catalyzed intramolecular cyclization

Enantioselective or diastereoselective intramolecular cyclization of functionalized secondary phosphines or their borane adducts catalyzed by chiral Pd(diphosphine) complexes gave P-stereogenic benzophospholanes in up to 70% ee. These results provide a new method for the synthesis of chiral phospholanes, which are valuable ligands in asymmetric catalysis. [reaction: see text]     

C2-symmetric bissulfoximines as ligands in copper-catalyzed enantioselective Diels-Alder reactions

[reaction: see text] Bissulfoximines have been used as chiral ligands in copper-catalyzed enantioselective Diels-Alder reactions between acryloyl-2-oxazolidinones and cyclopentadiene. After optimizing the ligand structure, the metal source, the counterions, and the solvent, products with up to 93% ee have been obtained.     

Development of a new class of chiral phosphorus ligands: P-chirogenic diaminophosphine oxides. A unique source of enantioselection in Pd-catalyzed asymmetric construction of quaternary carbons

[reaction: see text] We have recently developed a new class of chiral phosphorus ligands: P-chirogenic diaminophosphine oxides. These pentavalent phosphorus compounds have been successfully applied to Pd-catalyzed asymmetric construction of tertiary and quaternary carbons. The actual ligand structure was the trivalent phosphorus species 17, which was generated in situ by BSA-induced P(V) to P(III) transformation of 6, the preligand. Detailed mechanistic studies, including asymmetric amplification and initial rate kinetics, revealed that complex 18 [Pd-17 (1:2) complex] was the active catalyst. The important function of the nitrogen atom on the sidearm in the ligands was also clarified. The source of enantioselection in the construction of asymmetric quaternary carbons was the secondary ligand substrate interaction mediated by N-Zn coordination.     

Asymmetric Henry reaction catalyzed by C2-symmetric tridentate bis(oxazoline) and bis(thiazoline) complexes: metal-controlled reversal of enantioselectivity

[reaction: see text] C(2)-symmetric tridentate bis(oxazoline) and bis(thiazoline) ligands with a diphenylamine backbone have been investigated in the catalytic asymmetric Henry reaction of alpha-keto esters with different Lewis acids. Their Cu(OTf)(2) complexes furnished S enantiomers, while Et(2)Zn complexes afforded R enantiomers, both of them with higher enantioselectivities (up to 85% ee). Reversal of enantioselectivity in asymmetric Henry reactions was achieved with the same chiral ligand by changing the Lewis acid center from Cu(II) to Zn(II). The results show that the NH group in C(2)-symmetric tridentate chiral ligands plays a very important role in controlling both the yields and enantiofacial selectivity of the Henry products.     

Tripodal borate ligands from tris(dimethylamino)borane: the first synthesis of a chiral tris(methimazolyl)borate ligand, and the crystal structure of a single diastereomer pseudo-C3-symmetric Ru(II) complex

The activation of tris(dimethylamino)borane towards reaction with a chiral methimazole by N-methylimidazole has been used to prepare the first example of a chiral tris(methimazolyl)borate ligand. Coordination of this neutral ligand to Ru(II) has been achieved by reaction with [(p-cymene)RuCl(2)](2) to provide a single diastereomer complex in which the chirality of the methimazolyl substituents dictate the chirality of the bicyclo[3.3.3]cage formed by the ligand on coordination to the metal. The alternative approach to chiral tris(methimazolyl)borate ligands involving the introduction of a chiral group onto the boron atom has been explored by replacing N-methylimidazole in the above reaction by chiral oxazolines as activating bases in reaction with simple methimazole. However, although the B(NMe(2))(3) is activated to reaction with methimazole by these oxazolines, an intramolecular oxazoline ring-opening by a coordinated methimazolyl sulfur occurs and prevents the successful synthesis of these ligands.