N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺的合成及除草活性

以2-(4-羟基苯氧)丙酸为原料,设计合成了16个新的手性N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺化合物,其化学结构经核磁共振、色谱-质谱、红外光谱及元素分析确证.初步生物活性测定结果表明,合成的化合物在2.25×103g/ha剂量时对单子叶杂草马唐(Digitaria sanguinalis)、稗草(Echinochloa crus-galli)及狗尾草(Setaria viridis)等均具有90%以上的活性;进一步活性及作物安全性测试表明,化合物(R)-(+)-N-[(6-氯吡啶-3-基)甲基]-2-[4-(3-氯-5-三氟甲基吡啶-2-基氧基)苯氧基]丙酰胺(2b)的除草活性高于噁唑酰草胺,且对水稻茎叶处理安全,同时对水稻田主要杂草千金子的活性远高于氰氟草酯;化合物的除草活性与立体构型有关,R构型为活性构型.     

含联吡啶，Eu(III)或Gd(III)的手性高分子配合物的合成及荧光性质研究

手性高分子P–1由(R)-5,5′-二溴-6,6′-二(4-三氟甲基苯基)-2,2′-二正辛氧基-1,1′-联萘(R–M–1)和5,5′-二乙烯基-2,2′-联吡啶(M–2)通过Pd催化的Heck偶合反应合成得到,高分子配合物P-2和P-3由高分子P-1与Eu(TTA)3·2H2O和Gd(TTA)3·2H2O (TTA– = 2-噻吩甲酰三氟丙酮)反应生成。手性高分子P-1能发射强的蓝色荧光,这是由于手性重复单元(R)-6,6′-二(4-三氟甲基苯基)-2,2′-二正辛氧基-1,1′-联萘和单元2,2′-联吡啶通过亚乙烯基桥连形成共轭高分子结构造成的。在不同的激发波长激发下,含Eu(III)的高分子配合物P–2不仅显示高分子荧光,还可显示Eu(III) (5D0→7F2)特征荧光。含Gd(III)的高分子配合物P–3仅发射高分子荧光。基于高分子及含RE(III)的高分子配合物的荧光性质研究发现,共轭高分子并没有把能量转移到Eu(III)或Gd(III) 配合物部分,只发射它自身的荧光,含Eu(III)的高分子配合物P–2发射Eu(III) (5D0→7F2)特征荧光能量主要来源于配阴离子TTA–。     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

SpinPHOX/Ir(Ⅰ)催化的2-羟甲基-3-芳基丙烯酸的不对称氢化

光学活性的2-羟甲基-3-芳基丙酸类化合物是许多手性药物的关键合成中间体,但到目前为止其不对称合成方法大多存在对映选择性不高及/或底物范围有限等问题.报道了手性SpinPHOX/Ir(I)络合物在一系列2-羟甲基-3-芳基丙烯酸的不对称氢化中表现出优良的催化性能,取得完全的底物转化和良好到优秀的对映选择性(高达95%ee).对于同一2-羟甲基-3-芳基丙烯酸底物的不对称氢化,使用中心手性相同但螺环骨架上的轴手性相反的催化剂分别以优良的对映选择性获得构型相反的产物,从而为光学活性2-羟甲基-3-芳基丙酸及相关手性药物的不对称合成提供了一条简便高效的途径.     

手性双氨基醇-Et2Zn催化的不对称直接羟醛缩合反应

以1,3-二溴丙酮和(2'S)-(二苯基羟甲基)-四氢吡咯为原料,合成了两种新型手性氨基醇1,3-双[(2'S)-(二苯基羟甲基)-1-四氢吡咯基]丙酮(3)和1,3-双[(2'S)-(二苯基羟甲基)-1-四氢吡咯基]-2-丙醇(4),总产率分别为39%和35%.手性双氨基醇3-/4-Et2Zn可催化未修饰醛、酮的不对称直接羟醛缩合反应,对映体过量最高9%.     

相转移催化法和手性催化加氢法立体选择性地合成Fmoc保护的(S)-3,5-二溴苯丙氨酸

通过两种不对称催化方法合成了(S)-3,5-二溴苯丙氨酸.一种方法是以二苯亚胺甘氨酸叔丁酯和3,5-二溴苄基溴为底物,在O-烯丙基-N-9-蒽甲基溴化辛可宁定催化下,经不对称烷基化反应得到了(S)-3,5-二溴苯丙氨酸的衍生物,ee值达到94.9%,重点优化了不对称相转移催化烷基化反应的条件,得到了最优反应条件.另一种方法是以2-乙酰胺基-3-(3,5-二溴苯基)丙烯酸为底物,在双(1,5-环辛二烯)-三氟甲磺酸铑(I)和(R)-N-二苯基膦-N-甲基-(S)-2-(二苯基膦)二茂铁基乙胺催化下加氢得到乙酰基保护的(S)-3,5-二溴苯丙氨酸,再进行水解反应,最终得到(S)-3,5-二溴苯丙氨酸.经Fmoc的保护,得到Fmoc保护的(S)-3,5-二溴苯丙氨酸,ee值达到94.7%.所述两种方法中,第一种方法产率较高,对映选择性也较高,适合应用于其他手性二卤代苯丙氨酸的合成.     

基于脯氨酸的新型手性叔胺N-氧化物合成

叔胺衍生的N-氧化物配体的结构多样性合成仍然是不对称催化领域最重要的课题之一。以光学纯的脯氨酰胺或羟脯氨酰胺1与各种取代的吡啶-2-甲醛2发生缩合环化反应，生成中间体3,然后中间体3中的氮原子在氧化剂m-CPBA(间氯过氧苯甲酸)的作用下发生氧化反应，合成了24个新型手性叔胺氮氧化合物4aa～4bk,总产率43%～58%,dr值为10/1～>20/1,其结构经¹H NMR,¹³C NMR和HR-MS(ESI-TOF)表征，化合物4ai的绝对构型(3S, 4R, 7aS)通过单晶X-射线衍射进行了进一步确定。该类化合物以L-脯氨酸衍生物作为手性源制备了手性N-氧化物，今后可以为金属不对称催化提供新配体筛选。     

D(-)-二吡啶甲基酒石酸酰胺在不对称氧化合成埃索美拉唑中的应用

D(-)-酒石酸二乙酯(1)分别与2-氨甲基吡啶和4-氨甲基吡啶反应,合成了D(-)-二吡啶甲基酒石酸酰胺2和3.分别以1～3为手性配体与钛酸异丙酯配合,催化过氧化氢异丙苯(CHP)不对称氧化埃索美拉唑前体(Eso-I)合成埃索美拉唑.结果表明,由配体2或3构成的催化体系在埃索美拉唑合成上显示出较高的催化活性和对映选择性.例如,当以2为配体,甲苯为溶剂,在优化的条件下进行反应时,Eso-I的转化率达84.7%,埃索美拉唑的选择性达91.8%,对映体过量值达89.0%.     

含氟咪唑啉型有机催化剂在不对称Aldol反应中的研究

手性1,2-二醇骨架是天然产物或生物活性分子构建过程中的重要骨架,而α-羟基酮参与的不对称Aldol缩合反应是实现手性1,2-二醇骨架的重要手段.设计并合成了含三氟甲基的咪唑啉型化合物,并将其应用于羟基丙酮和醛的不对称Aodol缩合反应.研究结果表明,当采用含氟咪唑啉(2R,4S)-4-苄基-1,2-二甲基-2-三氟甲基咪唑啉(1a)作为不对称Aldol反应的催化剂时,能够以产率高达96%、最高ee值达到99%及dr值达到15∶1的效率高效构建一系列顺式1,2-二醇产物.同时,我们也初步探讨了氟-氢键在不对称催化反应中的作用.     

吡啶高三蝶烯的合成

2-溴-4-甲基吡啶（1）经氯代和碘代反应合成了2-溴-4-碘甲基吡啶（3）,3和蒽酮（4）反应生成10,10-二（2-溴-4-吡啶甲基）-9（10H）蒽酮（5）,5在3 MPa下与NaOCH3反应得到10,10-二（2-甲氧基-4-吡啶甲基）-9（10H）蒽酮（6）,6经硼氢化钠还原得到蒽醇（7）,7在对甲苯磺酸催化...     

Synthesis and Asymmetric Enantioselective Addition of Chiral Polybinaphthyl and Polybinaphthol I.igands

Four chiral polymers P-1, P-2, P-3 and P-4 were synthesized by the polymerization of （S）-2,2＇-dioctoxy-1,1＇- binaphthyl-6,6＇-boronic acid （S-M-3） with （S）-6,6＇-dibromo-1,1＇-binaphthol （S-M-1）, （R）-6,6＇-dibromo-1,1＇- binaphthol （R-M-1）, （S）-3,3＇-diiodo-1,1＇-binaphthol （S-M-2） and （R）-3,3＇-diiodo-1,1＇-binaphthol （R-M-2） under Pd-catalyzed Suzuki reaction, respectively. All four polymers can show good solubility in some common solvents due to the nonplanarity of the polymers in the main chain backbone and flexible alkyl groups in the side chain. The analysis results indicate that specific rotation and circular dichroism （CD） spectral signals of the alternative S-S chiral polymers P-1 and P-3 are larger than those of S-R chiral polymers P-2 and P-4, but their UV-Vis and fluorescence spectra are almost similar. The results of asymmetric enantioselectivity of four polymers for diethylzinc addition to benzaldehyde indicate that catalytically active center is （R） or （S）-1, 1＇-binaphthol moieties.     

Optically Active Helical Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl]: New Ligand for Asymmetric Addition of Diethylzinc to Aryl Aldehyde

Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl] (L*) was obtained by taking off the protecting groups of poly[(S)‐3‐vinyl‐2,2′‐bis(methoxymethoxy)‐1,1′‐binaphthyl] (poly‐ 1 ). L* was proved to keep a stable helical conformation in solution. The application of helical L* in the asymmetric addition of diethylzinc to aldehydes has been studied. The catalytic system employing 10 mol% of L* and 150 mol% of Ti(OⁱPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes, giving up to 99% enantiomeric excess (ee) and up to 93% yield of the corresponding secondary alcohol at 0°C. The chiral polymer can be easily recovered and reused without loss of catalytic activity as well as enantioselectivity.     

Chiral Mesoporous Organosilica Nanospheres: Effect of Pore Structure on the Performance in Asymmetric Catalysis

(R)‐(+)‐1,1′‐Bi‐2‐naphthol ((R)‐(+)‐Binol)‐functionalized (Binol=2,2′‐dihydroxy‐1,1′‐binaphthyl) chiral mesoporous organosilica nanospheres with uniform particle size (100 to 300 nm) have been synthesized by co‐condensation of tetraethoxysilane and (R)‐2,2′‐di(methoxymethyl)oxy‐6,6′‐di(1‐propyl trimethoxysilyl)‐1,1′‐binaphthyl in a basic medium with cetyltrimethylammonium bromide as the template. Nanospheres with a radiative 2D hexagonal channel arrangement exhibit higher enantioselectivity and turnover frequency than those with a penetrating 2D hexagonal channel arrangement (94 versus 88 % and 43 versus 15 h^?1, respectively) in the asymmetric addition of diethylzinc to aldehydes. In addition, under similar conditions, the enantioselectivity of the nanospheres can be greatly improved as the structural order of the framework increases. These results clearly show that the structural order of nanospheres affects enantioselective reactions. The enantioselectivity of the nanospheres synthesized by the co‐condensation method is higher than that of nanospheres prepared by a grafting method and even higher than that of their homogeneous counterpart. These results indicate that the bite angle of (R)‐(+)‐Binol bridging in a more rigid porous network is in a more favorable position for achieving higher enantioselectivity. The efficiency of a co‐condensation method for the synthesis of high‐performance heterogeneous asymmetric catalysts is also reported.     

New chiral diphosphoramidite rhodium(I) complexes for asymmetric hydrogenation

Chiral 1,5‐cyclooctadiene rhodium(I) cationic complexes with C₂‐symmetric chelate diphosphoramidite ligands containing (R,R)‐1,2‐diaminocyclohexane as the backbone and two atropoisomeric biaryl units were easily synthesized and fully characterized by multinuclear one‐ and two‐dimensional NMR spectroscopy and elemental analysis. These complexes were used as catalysts in the asymmetric hydrogenation of dimethyl itaconate, methyl 2‐acetamidoacrylate and (Z)‐methyl‐2‐acetamido‐3‐phenylacrylate. The rhodium complexes derived from diphosphoramidite ligands that contain two (R) or (S) BINOL (2,2′‐dihydroxy‐1,1′‐binaphthyl) units proved to be efficient catalysts, giving complete conversion and very good enantioselectivity (up to 88% ee). An uncommon positive H₂ pressure effect on the enantioselectivity was observed in the hydrogenation of dimethyl itaconate catalyzed by Rh‐complex with diphosphoramidite ligand that contains two (S)‐binaphthol moieties. Copyright © 2014 John Wiley & Sons, Ltd.     

Design and synthesis of chiral poly(binaphthyl salen zinc complex) and application of the asymmetric field based on its helical conformation to a catalytic asymmetric reaction

According to a rational design of helices (i.e., fusing C₂ chiral binaphthyl units and metallosalen complexes inevitably results in the formation of helical polymers), chiral poly(binaphthyl salen zinc complex)es ( 3 -Zn) were synthesized from an (R)-3,3′-diformylbinaphthol derivative, α,ω-diamines, and zinc acetate or diethylzinc. Their helical structures were well supported by their infrared, ultraviolet, and circular dichroism spectra, in addition to MM calculations and a CPK model study. The catalysis of 3 -Zn during the asymmetric addition of diethylzinc to aldehydes was investigated. In the presence of 5 unit mol % 3 -Zn, diethylzinc reacted with benzaldehyde to yield 1-phenyl-1-propanol in high yields (∼100%) and with high enantioselectivity (∼95%). The asymmetric yield of 1-phenyl-1-propanol increased significantly as the temperature was lowered, whereas both the asymmetric yield and the absolute configuration were drastically changed as the structure of the diamine unit of 3 -Zn was varied. Several aromatic aldehydes were converted into their corresponding alcohols with high enantioselectivity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4693–4703, 2004     

Polymer‐based fluorescence sensors incorporating chiral binaphthyl and benzo[2,1,3]thiadiazole moieties for Hg2+ detection

Three chiral polymers P‐1 , P‐2 , and P‐3 could be obtained by the polymerization of (R)‐6,6′‐dibutyl‐3,3′‐diiodo‐2, 2′‐binaphthol (R‐M‐1) , (R)‐6,6′‐dibutyl‐3,3′‐diiodo‐2,2′‐bisoctoxy‐1,1′‐binaphthyl ( R‐M‐2 ), and (R)‐6,6′‐dibutyl‐3,3′‐diiodo‐2,2′‐bis (diethylaminoethoxy)‐1,1′‐binaphthyl ( R‐M‐3 ) with 4,7‐diethynyl‐benzo[2,1,3]‐thiadiazole ( M‐1) via Pd‐catalyzed Sonogashira reaction, respectively. P‐1 , P‐2 , and P‐3 can show pale red, blue–green, and orange fluorescence. The responsive optical properties of these polymers on various metal ions were investigated by fluorescence spectra. Compared with other cations, such as Co²⁺, Ni²⁺, Ag⁺, Cd²⁺, Cu²⁺, and Zn²⁺, Hg²⁺ can exhibit the most pronounced fluorescence response of these polymers. P‐1 and P‐2 show obvious fluorescence quenching effect upon addition of Hg²⁺, on the contrary, P‐3 shows fluorescence enhancement. Three polymer‐based fluorescent sensors also show excellent fluorescence response for Hg²⁺ detection without interference from other metal ions. The results indicate that these kinds of tunable chiral polybinaphthyls can be used as fluorescence sensors for Hg²⁺ detection. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 997–1006, 2010     

Catalytic Enantioselective Synthesis of a 3‐Aryl‐3‐benzyloxindole (=3‐Aryl‐3‐benzyl‐1,3‐dihydro‐2H‐indol‐2‐one) Exhibiting Antitumor Activity

A palladium‐catalyzed intramolecular α‐arylation of an amide in the presence of a bulky chiral N‐heterocyclic carbene ligand is the key step in the first catalytic synthesis of (3R)‐6‐chloro‐3‐(3‐chlorobenzyl)‐1,3‐dihydro‐3‐(3‐methoxyphenyl)‐2H‐indol‐2‐one ((R)‐ 5 ). This oxindole, in racemic form, had been shown previously to be an anticancer agent. (R)‐ 5 was obtained with an overall yield of 45% and with 96% enantioselectivity.     

Synthesis of Novel 1,4‐Bissulfonamide Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

Several novel chiral sulfonamide ligands based on (1R,2S,4R,5S)‐1,4‐diamino‐2,5‐dimethylcyclohexane skeleton have been synthesized and their application in the enantioselective addition of diethylzinc to aldehydes was investigated in the presence of Ti(OⁱPr)₄. The effect of ligands, temperature and the loading amount of ligands was studied. Under optimized conditions, enantioselective addition of diethylzinc with various aryl aldehydes and aliphatic aldehydes proceeded smoothly and afforded chiral secondary alcohols in up to 88% ee.     

A Solid State Polymer‐Coated Electrode Containing a Chiral Crown Ether Derivative for Enantioselective Detection of Phenylglycine Methyl Ester Isomer

All solid‐state enantioselective electrode (ASESE) based on a newly synthesized chiral crown ether derivative ((R)‐(?)‐(3,3′‐diphenyl‐1,1′‐binaphthyl)‐23‐crown‐6 incorporating 1,4‐dimethoxybenzene) was prepared and characterized by potentiometry. The ASESE clearly showed enantiomer discrimination for methyl esters of alanine, leucine, valine, phenylalanine, and phenylglycine, where the enantioselectivity for phenylglycine methyl ester was the highest (K_R,S=8.5±7.1%). Experimental parameters of ASESE for the analysis of (R)‐(?)‐phenylglycine methyl ester were optimized. The optimized ASESE showed a slope of 55.3±0.2 mV/dec for (R)‐(?)‐phenylglycine methyl ester in the concentration range of 1.0×10^?5–1.0×10^?2 M and the detection limit was 9.0×10^?6 M. The ASESE showed good selectivity for (R)‐(?)‐phenylglycine methyl ester against inorganic cations and various amino acid methyl esters. The concentration of (R)‐(?)‐phenylglycine methyl ester was determined in the mixture of (R)‐(?) and (S)‐(+)‐phenylglycine methyl ester, which ratios varied from 2 : 1 to 1 : 9. The lifespan of the electrode was alleged to be 30 days.