Synthesis of quinoxaline derivatives catalyzed by PEG-400

<正>Polyethylene glycol(PEG) was found to be an effective catalyst for the condensation of 1,2-diamines with 1,2-dicarbonyl compounds to afford the corresponding quinoxaline derivatives in excellent yields under mild reaction conditions.     

Efficient enantioselective synthesis of 3-aminochroman derivatives through ruthenium-Synphos catalyzed asymmetric hydrogenation

A highly enantioselective asymmetric hydrogenation of various trisubstituted enamides derived from chroman-3-ones promoted by cationic Ru-Synphos catalysts is reported. This atom-economical and clean method provides an efficient route to optically active 3-aminochroman derivatives, which are important pharmacophores found in numerous drug candidates, in high chemical yields and enantiomeric excesses up to 96%.     

Metal-free asymmetric hydrogenation and hydrosilylation catalyzed by frustrated Lewis pairs

The activation of H₂ for the catalytic hydrogenation of unsaturated compounds is one of the most useful reactions in both academia and chemical industry, which has long been predominated by the transition-metal catalysis. However, metal-free hydrogen activation represents a formidable challenge, and has been less developed. The recent emerging chemistry of frustrated Lewis pairs (FLPs) with a combination of sterically encumbered Lewis acids and Lewis bases provides a promising approach for metal-free hydrogenation due to their amazing abilities for the challenging H₂ activation. In the past several years, the hydrogenation of a wide range of unsaturated compounds using FLP catalysts has been successfully developed. Despite these advances, the corresponding asymmetric hydrogenation is just in its start-up step. Similar to the mode of HH bond activation, SiH bond can also be activated by FLPs for the hydrosilylation of ketones and imines. But its asymmetric version is also not well-solved. This Letter will outline the recent important progress of metal-free catalytic asymmetric hydrogenation and hydrosilylation using FLP catalysts.     

General asymmetric hydrogenation of alpha-branched aromatic ketones catalyzed by TolBINAP/DMAPEN-ruthenium(II) complex

[reaction: see text] A catalyst system consisting of RuCl2[(S)-tolbinap][(R)-dmapen] and t-C4H9OK in 2-propanol effects asymmetric hydrogenation of arylglyoxal dialkylacetals to give the alpha-hydroxy acetals in up to 98% ee. Hydrogenation of racemic alpha-amidopropiophenones under dynamic kinetic resolution predominantly gives the syn alcohols in up to 99% ee and >98% de, while the reaction of racemic bezoin methyl ether gives the anti alcohols in excellent stereoselectivity.     

ZnCl2催化木质素磺酸盐加氢液化的溶剂效应

选用ZnCl₂为催化剂在高压反应釜中进行加氢液化反应,利用GC-MS和红外光谱技术,研究溶剂极性及供氢能力对木质素磺酸盐液化产率及产物的影响。产率分析表明,极性溶剂有利于木质素液化转化,供氢溶剂有利于提高轻馏分产率,水溶剂条件下木质素液化转化率最高,甲醇溶剂体系条件下轻馏分产率最高,相对最低液化转化率及轻馏分产率的1,4二氧六环溶剂体系分别提高2.0倍和1.9倍。GC-MS分析表明,中等极性溶剂有利于中间产物溶解稳定,供氢溶剂四氢萘通过释放氢自由基结合稳定中间产物。乙醇溶剂条件下中间产物相对含量是48.76%,相对最低含量水溶剂体系提高2.2倍。红外光谱分析表明,醇类溶剂参与反应,焦油产物羟基峰强度增强。     

联萘衍生物作为手性配体在不对称氢化中的应用

综述了近年来联萘衍生物作为手性配体构成的金属络合物在前手性烯、酮及亚胺的不对称氢化反应中的应用。     

Structure effect of TsDPEN derivatives on enantioselectivity of asymmetric transfer hydrogenation

TsDPEN derivative (3,3′,5,5′-TMTsDPEN) was synthesized and applied in asymmetric transfer hydrogenation of ketones. The influence of chiral ligands’ NCCN dihedral angles to the enantioselectivities of the reaction was discussed.     

Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation

5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Brönsted acid additive was found to be a key factor to obtain high enantioselectivity.     

Efficient asymmetric transfer hydrogenation of activated olefins catalyzed by ruthenium amido complexes

The asymmetric transfer hydrogenation of activated olefins with chiral ruthenium amido complexes (Noyori catalyst) using formic acid-triethylamine azeotrope as hydrogen source resulted in excellent yields and high enantioselectivities (up to 88.5%).     

Heterogeneous asymmetric hydrogenation of heteroaromatic methyl ketones catalyzed by cinchona-modified iridium catalysts

A heterogeneous iridium catalyst was synthesized with silica particles as support for the hydrogenation of heteroaromatic methyl ketones. The catalyst and support were characterized by solid-state NMR, HTEM, SEM, XPS, and BET. A series of heteroaromatic methyl ketones were investigated at room temperature. The catalytic system was effective and more than 99% conversion and up to 83.6% enantioselectivity were obtained in the hydrogenation of heteroaromatic methyl ketones.     

Iridium catalyzed asymmetric hydrogenation of cyclic imines of benzodiazepinones and benzodiazepines

Highly enantioselective Ir-catalyzed hydrogenation of seven-membered cyclic imines of benzodiazepinones and benzodiazepines was achieved with up to 96% ee. This method provides a direct access to synthesize a range of chiral cyclic amines existing in numerous important natural products and clinical drugs.     

Mechanism of asymmetric hydrogenation of ketones catalyzed by BINAP/1,2-diamine-rutheniumII complexes

Asymmetric hydrogenation of acetophenone with trans-RuH(eta(1)-BH(4))[(S)-tolbinap][(S,S)-dpen] (TolBINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl; DPEN = 1,2-diphenylethylenediamine) in 2-propanol gives (R)-phenylethanol in 82% ee. The reaction proceeds smoothly even at an atmospheric pressure of H(2) at room temperature and is further accelerated by addition of an alkaline base or a strong organic base. Most importantly, the hydrogenation rate is initially increased to a great extent with an increase in base molarity but subsequently decreases. Without a base, the rate is independent of H(2) pressure in the range of 1-16 atm, while in the presence of a base, the reaction is accelerated with increasing H(2) pressure. The extent of enantioselection is unaffected by hydrogen pressure, the presence or absence of base, the kind of base and coexisting metallic or organic cations, the nature of the solvent, or the substrate concentrations. The reaction with H(2)/(CH(3))(2)CHOH proceeds 50 times faster than that with D(2)/(CD(3))(2)CDOD in the absence of base, but the rate differs only by a factor of 2 in the presence of KO-t-C(4)H(9). These findings indicate that dual mechanisms are in operation, both of which are dependent on reaction conditions and involve heterolytic cleavage of H(2) to form a common reactive intermediate. The key [RuH(diphosphine)(diamine)](+) and its solvate complex have been detected by ESI-TOFMS and NMR spectroscopy. The hydrogenation of ketones is proposed to occur via a nonclassical metal-ligand bifunctional mechanism involving a chiral RuH(2)(diphosphine)(diamine), where a hydride on Ru and a proton of the NH(2) ligand are simultaneously transferred to the C=O function via a six-membered pericyclic transition state. The NH(2) unit in the diamine ligand plays a pivotal role in the catalysis. The reaction occurs in the outer coordination sphere of the 18e RuH(2) complex without C=O/metal interaction. The enantiofaces of prochiral aromatic ketones are kinetically differentiated on the molecular surface of the coordinatively saturated chiral RuH(2) intermediate rather than in a coordinatively unsaturated Ru template.     

Enantioselective hydrogenation of indoles derivatives catalyzed by Walphos/rhodium complexes

The enantioselective hydrogenation of indole esters has been carried out efficiently in the presence of a rhodium catalyst modified by Walphos-type chiral ligands. The addition of a base can be beneficial in some catalytic conditions.     

An efficient method for the synthesis of quinoxaline derivatives catalyzed by titanium silicate-1

Research on Chemical Intermediates - A series of quinoxaline derivatives were efficiently synthesized by convenient and simple procedure in excellent yields using 1 wt.% of titanium silicate (TS-1)...     

Dendritic MonoPhos: synthesis and application in Rh-catalyzed asymmetric hydrogenation

A new class of dendritic monodentate phosphoramidite ligands were synthesized through substitution of the dimethylamino moiety in MonoPhos by the Fréchet-type dendritic wedge and applied in the asymmetric hydrogenation of α-dehydroamino acid esters and dimethyl itaconate. High enantioselectivities (up to 97.9% ee) and catalytic activities (up to 4850 h⁻¹ TOF) were achieved, which are better or comparable to those obtained from MonoPhos. The third generation dendrimer catalyst gave the slightly lower catalytic activity relative to the lower generation ones. The steric shielding by the dendrimer could stabilize the rhodium complex against decomposition caused by hydrolysis in a protic solvent. The inactive catalysts (RhL₃ and RhL₄) were activated by addition of a free metal precursor Rh(COD)₂BF₄, and showed high enantioselectivities and catalytic activities.     

Additive effects of amines on asymmetric hydrogenation of quinoxalines catalyzed by chiral iridium complexes

The additive effects of amines were realized in the asymmetric hydrogenation of 2-phenylquinoxaline, and its derivatives, catalyzed by chiral cationic dinuclear triply halide-bridged iridium complexes [{Ir(H)[diphosphine]}(2) (μ-X)(3) ]X (diphosphine=(S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(S)-BINAP], (S)-5,5'-bis(diphenylphosphino)-4,4'-bi-1,3-benzodioxole [(S)-SEGPHOS], (S)-5,5'-bis(diphenylphosphino)-2,2,2',2'-tetrafluoro-4,4'-bi-1,3-benzodioxole [(S)-DIFLUORPHOS]; X=Cl, Br, I) to produce the corresponding 2-aryl-1,2,3,4-tetrahydroquinoxalines. The additive effects of amines were investigated by solution dynamics studies of iridium complexes in the presence of N-methyl-p-anisidine (MPA), which was determined to be the best amine additive for achievement of a high enantioselectivity of (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline, and by labeling experiments, which revealed a plausible mechanism comprised of two cycles. One catalytic cycle was less active and less enantioselective; it involved the substrate-coordinated mononuclear complex [IrHCl(2) (2-phenylquinoxaline){(S)-BINAP}], which afforded half-reduced product 3-phenyl-1,2-dihydroquinoxaline. A poorly enantioselective disproportionation of this half-reduced product afforded (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline. The other cycle involved a more active hydride-amide catalyst, derived from amine-coordinated mononuclear complex [IrCl(2) H(MPA){(S)-BINAP}], which functioned to reduce 2-phenylquinoxaline to (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline with high enantioselectivity. Based on the proposed mechanism, an Ir(I) -JOSIPHOS (JOSIPHOS=(R)-1-[(S(p) )-2-(dicyclohexylphosphino)ferrocenylethyl]diphenylphosphine) catalyst in the presence of amine additive resulted in the highest enantioselectivity for the asymmetric hydrogenation of 2-phenylquinoxaline. Interestingly, the reaction rate and enantioselectivity were gradually increased during the reaction by a positive-feedback effect from the product amines.     

Asymmetric iodocyclization catalyzed by salen-CrIIICl: its synthetic application to swainsonine

The previously developed enantioselective iodocyclization of gamma-hydroxy-cis-alkenes required 30 mol% of (R,R)-salen-Co(II) complex as chiral catalyst and 0.75 equivalent of N-chlorosuccinimide (NCS) as activator to produce 2-substituted tetrahydrofurans with 61 to 90% ee. Due to the considerable loading amount of the Co(II) complex, another more effective catalyst was pursued by screening (R,R)-salen-transition metal complexes. When 10 mol% of the catalysts were applied with 0.5 equivalent of NCS, a higher level of stereoselectivity was attained with the corresponding Cr(III)Cl (84% ee), Mn(II)Cl (52% ee) and Co(II) complexes (66% ee). Refinement of the conditions established a novel catalytic enantioselective iodocyclization protocol using iodine in the presence of 7 mol% of (R,R)-salen-Cr(III)Cl complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93% ee.     

The effect of substituents of immobilized Rh complexes on the asymmetric hydrogenation of acetophenone derivatives

Using a modified Augustine’s method variously substituted Rh complexes were anchored on Al₂O₃ support. The prepared catalysts were characterized by spectroscopic methods and were applied in the hydrogenation of several acetophenone derivatives (p-CF₃-acetophenone, acetophenone, p-NH₂-acetophenone). Enantioselective C=O hydrogenations were observed with reasonable activity and selectivity on all heterogenized complexes, e.e. up to 80%. At the same time the immobilized samples showed the advantages of the heterogeneous systems: easy handling and recyclability.