手性二胺修饰的镍配合物催化苯乙酮及其衍生物的不对称加氢反应

本文研究了由手性修饰剂(S,S)D-DPEN(DPEN:1,2一二苯基乙二胺)在反应条件下与NiCl2(PPh3)2原位生成的手性催化剂对苯乙酮及其衍生物不对称加氢反应的催化性能,考察了反应温度、反应压力、(S,S)-DPEN浓度等变化因素对催化活性和对映选择性的影响。结果表明,在15℃,氢气压力为8.0MPa,乙醇作溶剂时,苯乙酮加氢产物(R)-苯乙醇的对映选择性达到了77.2%e.e。     

由(1R,2S)-麻黄碱制备的硼杂噁唑烷催化甲硼烷不对称还原苯乙酮

由(1R,2S)-麻黄碱制得了五个新的手性硼杂(口恶)唑烷1～5,它们催化甲硼烷不对称还原苯乙酮,获得了高产率的具有38.5～72.4％e.e.的R-1-苯基乙醇。讨论了催化剂的结构-活性关系及反应参数(催化剂用量、反应温度)对还原反应对映选择性的影响。     

由(1R, 2S)-麻黄碱制备的硼杂恶唑烷催化甲硼烷不对称还原苯乙酮

由(1R, 2S)-麻黄碱制得了五个新的手性硼杂恶唑烷1~5, 它们催化甲硼烷不对称还原苯乙酮, 获得了高产率的具有38.5~72.4%e. e.的R-1-苯基乙醇。讨论了催化剂的结构-活性关系及反应参数(催化剂用量、反应温度)对还原对应对映选择性的影响。     

SDP配体在铑催化的Pauson-Khand反应中的应用

研究了SDP作为双膦配体与金属铑形成的手性催化剂在不对称Pauson-Khand反应中的催化活性和对映选择性, 并考察了影响反应活性和对映选择性的各种因素. 结果表明, SDP配体对铑催化的Pauson-Khand反应是一种有效的手性配体, 它与铑生成的手性催化剂能在1大气压的一氧化碳气氛中, 将一系列1,6-烯炔化合物转化为相应的双环戊烯酮, 反应的对映选择性较高. 在SDP配体中苯环上引入取代基导致反应的对映选择性降低, 但是当取代基为甲氧基时, 催化剂的活性得到明显提高. 溶剂实验表明1,2-二氯乙烷是理想的反应溶剂. 催化剂的阴离子对催化剂活性和对映选择性也有十分重要的影响, 采用六氟锑酸根时, 反应的对映选择性最高.     

二溴和二碘取代的手性Schiff碱-钒(Ⅳ)络合物催化硫醚不对称氧化

 由廉价的手性氨基醇与3,5-二溴或3,5-二碘水杨醛缩合得到配体,配体与VO(acac)2按一定比例络合形成络合物催化剂,考察了室温下该催化剂对芳基甲基硫醚不对称氧化反应的催化性能. 结果表明,当VO(acac)2/配体摩尔比为1/2, 并且以H2O2作为氧源时,催化剂具有较高的活性和中等至很高的对映选择性. 与(S)-苯丙氨醇和(R)-亮氨醇衍生得到的配体相比,由(S)-缬氨醇得到的配体具有更高的对映选择性. 在缓慢滴加H2O2的条件下,以3,5-二碘水杨醛和(S)-缬氨醇缩合得到的Schiff碱为配体,以苯甲硫醚和对溴苯甲硫醚为底物时,产物的ee值分别为88%和92%. 研究表明,与Fe(acac)3/Schiff碱体系不同,向VO(acac)2/Schiff碱催化体系中加入羧酸或羧酸盐类化合物并不能改善催化剂的催化性能.     

手性氨基醇衍生物催化苯基锂与亚胺的不对称加成反应研究

本文报道几种不同结构的手性氨基醇衍生物在亚胺与苯基锂不对称加成反应中的应用,并对配体结构与对映选择性的关系进行了初步探索,研究结果表明,在双手性配体中,具有反式(S,S)构型的配体催化效果优于顺式(S,R)。     

D-甘露醇衍生的手性亚磷酸酯配体：合成及应用于铑催化α-脱氢氨基酸酯不对称氢化

以1,2:5,6-双亚环己基-D-甘露醇为手性骨架,合成含有联苯基团的新型手性tropos配体;分别以1,2:5,6-双异丙叉-D-甘露醇和1,2:5,6-双亚环己基-D-甘露醇为原料,合成系列双齿亚磷酸酯配体,将这些配体应用于铑催化α-乙酰氨基肉桂酸甲酯5a和α-苯酰氨基肉桂酸甲酯5b氢化反应中,考察配体结构,溶剂,底物/催化剂的摩尔比对反应对映选择性的影响,优化了反应条件;在底物是α-乙酰胺基肉桂酸甲酯时,配体的双异丙叉骨架与(R)-联萘部分是匹配组合,反应对映选择性高达93.5%.在优化的反应条件下,尝试七个苯环含不同取代基团的底物,无论供电子基团在芳环的邻位还是对位,其氢化产物的对映选择性均高于相应位置为吸电子基团的.     

手性螺二氢茚双膦配体在钌催化酮的不对称氢化反应中的应用研究

羰基化合物的不对称催化氢化是获得光学活性醇类化合物的极为有效的方法之一.在对芳基烷基酮的不对称催化氢化反应的研究中,Noyori等开发出一种非常有效的不对称催化氢化体系,即手性双膦-钌-双胺催化体系.该催化体系是一个具有高转化数、高转化频率以及高对映选择性的催化体系,它能催化氢化烷基酮、芳基酮、杂环芳酮等多种含羰基的潜手性底物[1].我们研究小组合成了一类具有螺二氢茚骨架的手性螺环双膦配体SDP,当这类配体应用于该氢化反应时,不但获得了极高的对映选择性(最高达99.5?),而且转化数也很高(TON高达100000)[2].在研究RuCl2-[(S)-Xyl-SDP][R,R)-DPEN)]络合物催化氢化芳基烷基酮时,发现当用NaOBu-t作碱时,催化氢化反应的速度明显比用KOBu-t作碱时要快.这与Hartmann和Chen等[3]在RuCl2-[(S)-BINAP][(S,S)-DPEN]催化氢化苯乙酮反应中的结果正好相反.我们进一步采用动力学的方法,深入研究了碱金属阳离子对苯乙酮催化氢化反应速率的影响.研究结果表明:双膦配体中P-芳环上的取代基对碱金属阳离子影响氢化反应速率的顺序产生明显影响.     

螺[4,4]-1,6-壬二烯骨架手性双膦配体的合成

从方便易得的原料出发,以钯催化的烯基三氟甲磺酸酯与二苯基膦氧化物的偶联反应为关键步骤,合成了螺[4,4]-1,6-壬二烯骨架的手性双膦配体1.其中,关键中间体5的拆分是通过半制备手性液相色谱实现的,并通过该化合物的X射线单晶衍射分析确定了其中螺碳原子的绝对构型.配体(S)-1的Rh(I)络合物在α-乙酰氨基肉桂酸的氢化中表现出中等的对映选择性(53%ee).配体(S)-1的Cu(I)络合物能以较好的反应活性实现苯乙酮的不对称氢化,产物的对映体过量可以达到67%.     

手性双哌啶衍生物用于甲基三氧化铼催化烯烃不对称环氧化反应

以N-烷基-4-哌啶酮为原料,制备了几个手性双哌啶衍生物配体.以尿素-过氧化氢复合物(UHP)为氧化剂,甲醇为溶剂,将这些配体用于甲基三氧化铼(MTO)催化的前手性烯烃的环氧化反应,考察了各种反应参数对催化剂催化性能的影响.结果表明,手性双哌啶衍生物的加入可降低MTO的催化活性,但可提高环氧化物的选择性;这些配体对前手性烯烃的环氧化反应有较低的手性诱导作用,对映体过量值(ee值)只有4%-11%.讨论了对映选择性低的原因.     

Asymmetric hydrosilylation of styrenes catalyzed by palladium-MOP complexes: ligand modification and mechanistic studies

In the palladium-catalyzed asymmetric hydrosilylation of styrene (3a) with trichlorosilane, several chiral monophosphine ligands, (R)-2-diarylphosphino-1,1'-binaphthyls (2a-g), were examined for their enantioselectivity. The highest enantioselectivity was observed in the reaction with (R)-2-bis[3,5-bis(trifluoromethyl)phenyl]phosphino-1,1'-binaphthyl (2g), which gave (S)-1-phenylethanol (5a) of 98% ee after oxidation of the hydrosilylation product, 1-phenyl-1-(trichlorosilyl)ethane (4a). The palladium complex of 2g also efficiently catalyzed the asymmetric hydrosilylation of substituted styrenes on the phenyl ring or at the beta position to give the corresponding chiral benzylic alcohols of over 96% ee. Deuterium-labeling studies on the hydrosilylation of regiospecifically deuterated styrene revealed that beta-hydrogen elimination from 1-phenylethyl(silyl)palladium intermediate is very fast compared with reductive elimination giving hydrosilylation product when ligand 2g is used. The reaction of o-allylstyrene (9) with trichlorosilane catalyzed by (R)-2g/Pd gave (1S,2R)-1-methyl-2-(trichlorosilylmethyl)indan (10) (91% ee) and (S)-1-(2-(propenyl)phenyl)-1-trichlorosilylethanes (11a and 11b) (95% ee). On the basis of their opposite configurations at the benzylic position, a rationale for the high enantioselectivity of ligand 2g is proposed.     

Rhodium-catalyzed ring-opening reactions of N-boc-azabenzonorbornadienes with amine nucleophiles

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl](2) and (S,S')-(R,R')-C(2)-ferriphos (4a), the asymmetric ring-opening reaction of azabenzonorbornadienes (1a-m) with various aliphatic and aromatic amines (2a-l) proceeded with high enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine derivatives 3 in high yields. In the specific case of pyrrolidine as nucleophile, Et(3)NHCl was necessary as an additive for good reactivity and enantioselectivity. Additionally, a practical protocol was developed for the ring-opening of 1a with volatile amines at elevated temperatures and standard pressure, using R(2)NH(2)I and i-Pr(2)NEt. The experimental results showed that the nature of the chiral ligand has the significant impact on the reactivity of the catalyst and the use of excess amount (2.2 eq to Rh) of the chiral ligand plays an important role to improve the enantioselectivity in the present asymmetric reaction.     

Asymmetric allylic substitution catalyzed by C1-symmetrical complexes of molybdenum: structural requirements of the ligand and the stereochemical course of the reaction

Application of new chiral ligands (R)-(-)-12 a and (S)-(+)-12 c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 --> 6), led to excellent regio- and enantioselectivities (>30:1, < or =98 % ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements of the ligand and the mechanism are discussed. The application of single enantiomers of deuterium-labeled substrates (both linear 38 c and branched 37 c) and analysis of the products (41-43) by (2)H{(1)H} NMR spectroscopy in a chiral liquid crystal matrix allowed the stereochemical pathways of the reaction to be distinguished. With ligand (S)-(+)-12 c, the matched enantiomer of branched substrate was found to be (S)-5, which was converted into (R)-6 with very high regio- and stereoselectivity via a process that involves net retention of stereochemistry. The mismatched enantiomer of the branched substrate was found to be (R)-5, which was also converted into (R)-6, that is, with apparent net inversion, but at a lower rate and with lower overall enantioselectivity. This latter feature, which may be termed a "memory effect", reduced the global enantioselectivity in the reaction of the racemic substrate (+/-)-5. The stereochemical pathway of the mismatched manifold has been shown also to be one of net retention, the apparent inversion occurring through equilibration via an Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration leads to the memory effect and thus to lower enantioselectivity. Analysis of the mismatched manifold over the course of the reaction revealed that the memory effect is progressively attenuated with the nascent global selectivity increasing substantially as the reaction proceeds. The origin of this effect is suggested to be the depletion of CO sources in the reaction mixture, which attenuates turnover rate and thus facilitates greater equilibrium. The linear substrate was also converted into the branched product with net syn stereochemistry, as shown by isotopic labeling. An analogous process operates in the generation of small quantities of linear product from branched substrate.     

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral BINOL-derived zincate catalyst

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral metal complex is reported for the first time herein. Two novel semicrown chiral ligands 1a and 1b were synthesized from (S)- and (R)-BINOL, respectively, and then employed to catalyze the direct asymmetric aldol addition of aryl ketones to aryl aldehydes. Introduced with 2.0 equiv of diethylzinc, 1b had higher enantioselectivity than 1a. Up to 97% yield and up to 80% enantioselectivity were achieved.     

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.     

手性胺修饰的羟基磷灰石负载RuCl_2(TPP)_3催化不对称氢化苯乙酮

采用共沉淀法制备了手性胺(L-脯氨酸、D-脯氨酸、(1R,2R)-1,2-二苯基乙二胺二磺酸钠((1R,2R)-DPENDS)、(1S,2S)-1,2-二苯基乙二胺二磺酸钠((1S,2S)-DPENDS))修饰的羟基磷灰石(HAP).并采用傅里叶变换红外(FT-IR)光谱,扫描电子显微镜(SEM),X射线衍射(XRD)和比表面积测定(BET)等仪器分析手段对其进行表征.以手性胺修饰的羟基磷灰石做载体负载RuCl2(TPP)3催化苯乙酮不对称加氢反应,详细考察温度、压力、碱的浓度、手性胺负载量等条件对催化反应的影响.在氢气压力为5.0 MPa、30℃条件下反应4 h,苯乙酮的不对称加氢反应,可获得99.9%转化率和77.8%对映选择性,其结果优于对应的均相催化反应.实验结果证明,催化反应在载体表面完成,催化剂通过简单离心分离可循环使用.     

C2-symmetric recyclable organocatalyst for enantioselective Strecker reaction for the synthesis of α-amino acid and chiral diamine--an intermediate for APN inhibitor

Recyclable chiral amide-based organocatalyst 5 efficiently catalyzed asymmetric Strecker reaction of various aromatic and aliphatic N-benzhydrylimines with ethyl cyanoformate as cyanide source at -10 °C to give a high yield (95%) of α-aminonitriles with excellent chiral induction (ee, up to 99%) with the added advantage of recyclability. Based on experimental observations a probable mechanism was proposed for this reaction. This protocol with catalyst 5 was extended for the synthesis of (R)-phenylalanine and pharmaceutically important drug intermediate (R)-3-phenylpropane-1,2-diamine in high yield with high enantioselectivity.     

Synthesis of C3-symmetric tris(beta-hydroxy amide) ligands and their Ti(IV) complex-catalyzed enantioselective alkynylation of aldehydes

[reaction: see text]. A series of new chiral C3-symmetric tris(beta-hydroxy amide) ligands have been synthesized via the reaction of 1,3,5-benzenetricarboxylic chloride and optically pure amino alcohols (up to 96% yield). The asymmetric catalytic alkynylation of aldehydes with these new C3-symmetric chiral tris(beta-hydroxy amide) ligands and Ti (O(i)'Pr)4 was investigated. Ligand 4c synthesized from (1R,2S)-(-)-2-amino-1,2-diphenylethanol is effective for the enantioselective alkynylation of various aldehydes, and high enantioselectivity was obtained with aromatic aldehydes and alpha,beta-unsaturated aldehyde (up to 92% ee).     

Synthesis of 7,7’-Disubstituted BINAP and Their Application in Asymmetric Catalytic Reaction

The design of new chiral ligands plays a very important role in the development of transition metal catalyzed asymmetric synthesis. Many chiral diphosphine ligands have been prepared and applied in asymmetric catalytic reactions with excellent enantioselectivities. Among the chiral diphosphine ligands reported, BINAP was found to have been the widest application in the transition metal catalyzed reaction. Recently we have developed a novel oxovanadium (Ⅳ) complex catalyst for the oxidative …