新手性试剂R-(-)-β-三氟甲基-β-甲氧基-β-苯基乙胺的合成和研究

本文报道一种新的手性试剂 R-(-)-β-三氟甲基-β-甲氧基-β-苯基乙胺(TMPEA)。它是在吸取已有手性试剂优点的基础上设计合成的,具有下列优点:1.立体识别能力强,由它与多种手性有机酸生成的非对映异构酰胺,相应非对映基团的~1H和~(19)F NMR 位移差都较大。2.分子中 CF_3基团的~(19)F NMR 信号是尖锐的单峰,且出现在无质子共振信号干扰的区域。这两点都利于非对映基团信号的分别和精确积分。故在多数情况下,R-(-)-TMPEA 可以成功用于手性有机酸的对映体纯度测定。     

测定手性有机酸对映体纯度的新试剂

用NMR技术测定微量手性化合物的对映体纯度,已有多种方法。其中,加手性镧化物位移试剂法适用面最广,但对有机酸,结果常不理想。另一种使用较广的方法是加手性试剂,将样品中两对映体转变成非对映异构体,然后比较非对映基因NMR信号的强度,确定原样品中对映体的组成比例。国外已出售的手性试     

麻黄碱对映异构体的柱前手性衍生化-反相高效液相色谱法拆分

建立了一种用柱前手性衍生化－反相高效液相色谱法分析麻黄碱对映异构体的方法;以（一）－氯化酸薄荷醇酯作为手性衍生化试剂,（－）－麻黄碱与（＋）－麻黄碱衍生化后生成－对非对映异构体,选用Hypersil C18柱,以乙腈-水－乙酸－三乙胺（体积比29：20：0．2：0．01）为流动相,在254nm下检测,色谱经分经电喷雾离子阱多级质谱分析验证;非对称异构体色谱峰的保留时间分别为17．1min和18．3min,分离度为1．6;该法操作简单、快速、重现性好,可用于药品质量控制和对映体选择性药物动力学研究。     

NMR手性位移试剂Eu(facam)3的应用

应用核磁共振波谱法来测定有机化合物的光学对映体含量是很有意义的。通常,它有三种方法:①应用手性溶剂,②被测对映体形成非对映异构体方法,③手性位移试剂。Pirkle等应用的手性溶剂方法,虽可推测绝对构型,但往往由于对映位化学位移差值较小,不易准确测定含量。一般应用最广的Mosher试剂(光学活性α-甲氧基α-三氟甲基苯乙酸,MTPA)形成非对映异构体的方法,仅局限于测定醇或胺类化合物,此法有时还需普通位移试剂配合使用。手性位移试剂则可直接测定对映体的光学纯度。 1970年Whitesides和Lewist首先合成了手性位移试剂三-(3-叔丁基羟基亚甲基-d-樟脑)     

安非他明类毒品的手性对映体气相色谱-质谱分析

采用手性衍生化试剂：（S）（－）N－三氟乙酰－1－脯胺酰氯（TPC）和（R）（＋）－α-甲氧基－α－三氟甲基苯乙酸（MTPA）与安非他明类对映体衍生化产物,通过常规的GC／MS方法将其分离,本文较系统地考察了这两种手性试剂衍生化反应中溶剂、手性试剂用量、加热温度、反应时间等因素对安非他明类在体衍生化结果的影响。实现了Am、MAm、MDA、MDMA、MDEA、MBDB等几种毒品对映体间的良好分离。     

人血清白蛋白柱上药物的手性拆分

考察了４种酸性药物和１种中性药物对映体在人血清白蛋白手性固定相上的保留行为。这５种药物与人血清白蛋白结合的亲和力高，难于实现快速分离，作者提出在流动相中加入短链脂肪酸－正己酸，可快速手性拆分非诺洛芬、萘普生和布洛芬。酮基布洛芬对映体分离选择性随乙腈浓度升高而增大，流动相中加入适量异丙醇可使对映体选择性大大增加（α～１．２３），华法令同样可取得很好分离。     

用手性配体改性铝锂试剂对芳香酮的还原

用手性一元酮作辅助配体,与１,２,５,６－二丙酮甘ｉＡｌｈ５对芳香酮进行对映选择 的,得到光学活性产物８个。通过与α－乙酰氧基－Ｌ－丙酰氯生成非对映异构体酯,经气相色谱分析,芳酮挑学产率为２３．３￣７１．２％。初步探讨了配体之间对称性匹配的情况。     

以β-环糊精及其衍生物为手性选择剂毛细管电泳拆分几种药物的旋光对映体

在毛细管电泳中，采用β－环糊精（β－ＣＤ）及其衍生物为手性选择剂对扑尔敏、异丙嗪、二氧异丙嗪和氧氟沙星对映体进行了分离。优化了分离条件；讨论了环糊精空腔边缘与溶．质分子作用的基团的种类和分离效果的联系，通过计算手性分离的热力学常数比较了不同手性选择剂对扑尔敏对映体的分离能力。最后，讨论了乙腈在手性分离中的作用。     

有机锂试剂对二茂铁亚胺的不对称加成反应

研究了利用(－)-sparteine辅助的有机锂试剂对非手性二茂铁亚胺的对映选择性加成和对衍生于廉价的苯乙胺的手性二茂铁亚胺的非对映选择性加成反应. 对亚胺结构和实验条件对反应的影响进行了深入研究. 在有机锂试剂对非手性二茂铁亚胺的对映异构体选择性加成中得到了中等的对映选择性, 对衍生于(R)-苯乙胺的手性二茂铁亚胺的非对映选择性加成反应, 路易斯酸BF3•OEt2的添加对反应非常有利, 得到了非常好的非对映选择性.     

薄层色谱法拆分手性药物对映体

用性能稳定的薄层色谱用β-环糊精(β-CD)、硅胶手性固定相拆分手性药物对映体.在适当比例的乙腈-1%乙酸三乙胺(TEAA)、己烷-异丙醇、乙腈-甲醇-乙酸-三乙胺、甲醇-1%TEAA及乙腈-1%TEAA-三乙胺溶剂系统中展开,8种临床常用的手性药物对映体得到有效分离,对映异构体之间的相对比移值α为1.53～4.89.     

手性金属络合物催化不对称Baeyer-Villiger反应

Baeyer-Villiger反应是有机化学基本反应之一,但是催化不对称Baeyer-Villiger反应的研究尚处于起步阶段。本文按手性配体的不同,评述了手性金属络合物催化不对称Baeyer-Villiger反应的研究,特别是由外消旋或前手性酮制备光学活性内酯的研究进展。     

Chiral Diamine-catalyzed Asymmetric Aldol Reaction

A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine (1R,2R)-cyclohexane-1,2-diamine(6) and trifluoroacetic acid (TFA) was employed for asymmetric Aldol reaction in em-PrOH at room temperature. A loading of 10%(molar fraction) catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes, furnishing Aldol pro- ducts in moderate to high yields(up to >99%) with enantioselectivities of up to >99% and diastereoselectivities of up to 99:1.     

New Chiral Ligands with Nonstereogenic Chirotopic Centers for Asymmetric Synthesis

Pseudo- C ₂ -symmetrical ligands have been prepared efficiently: The attachment of the chiral alkyl group to the heteroatom (P or N) through a nonstereogenic, chirotopic carbon center facilitates their synthesis as the configuration at this carbon atom no longer needs to be controlled. Two such ligands were combined, for example, in the base 1 , which is especially useful for asymmetric deprotonation of prochiral ketones [Eq. (a)].     

Chiral terpene auxiliaries. Part 1: Highly enantioselective reduction of ketones with borane catalyzed by an oxazaborolidine derived from (−)-β-pinene

(1R,2S,3R,5R)-3-Amino-6,6-dimethyl-2-hydroxybicyclo[3.1.1]heptane was synthesized in three steps from (−)-β-pinene. It was used for the in situ generation of a B-methoxy-oxazaborolidine catalyst for the asymmetric reduction of alkyl-aryl ketones with borane-dimethyl sulfide complex. In the presence of 3 mol % of the catalyst, the product alcohols were obtained in high yields and with enantiomeric excesses in the range of 93-98%.     

Synthesis of New Chiral Phosphine Ligands and Their Application in Asymmetric Hydrogenation of Ketones

The design of new chiral ligands is the key 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 that have been reported, the atropisomeric C2-symmetric phosphines with a biaryl scaffold initiated by Noyori and co-workers with BINAP were found to have the widest application in the transition metal catalyze…     

Synthesis of new carbohydrate-derived ketones as organocatalysts in the enantioselective epoxidation of arylalkenes. Part 2: Chiral ketones from sugars

A range of new, somewhat complex, stereochemically varied, and structurally related carbohydrate-derived ketones were synthesised by a simple method from the carbohydrate precursor (d-gluco and d-galacto derivatives). The common skeleton possesses the keto function sited on a seven-membered ring fused to positions 2 and 3 of the sugar moiety. Their chirality transfer capability in the dioxirane-mediated epoxidation of arylalkenes was evaluated.     

光学活性胺膦配体的合成与在不对称催化中的应用

用邻二苯基膦苯甲醛与不同的手性二胺缩合,高产率地制备了一系列手性双胺双膦配体。这些配体分别与Ru(DMSO)4Cl2或[Rh(COD)Cl]2等反应,可制备相应的手性双胺双膦钌、铑配合物。在异丙醇溶液中,该C2-对称的手性双胺双膦钌、铑配合物是多种芳香酮不对称转移氢化的优化催化剂,反应产物手性芳香醇的转华裔经和对映选择性分别高达99%和98ee。     

New mannose-derived ketones as organocatalysts for enantioselective dioxirane-mediated epoxidation of arylalkenes. Part 3: Chiral ketones from sugars

New d-arabino-hexopyranosid-3-uloses were synthesized by a simple method from mannopyranoside derivatives. The common skeleton possesses a tunable alkoxy group as steric sensor on carbon 2 of the sugar. The new ketones were employed in the dioxirane-mediated epoxidation of a range of trans- and trisubstituted arylalkenes giving enantiomeric excesses from low to good (30-90%). The effect of the size of the steric sensor on the enantioselectivity was also studied. The least bulky group (methoxy group) enhanced the stereoselectivity (up to 90% ee toward triphenylethylene).     

RuCl_2[(S)-P-Phos]-[(S)-DAIPEN]催化芳香酮的不对称加氢反应

研究了钌-双膦-二胺配合物催化剂RuC1_2[(S)-P-Phos]-[(S)-DAIPEN][P-Phos:2,2',6,6'-四甲氧基-4,4'-双(二苯基膦基)-3,3'.二吡啶,DA肫N:1,1.二(4.甲氧苯基).2.异丙基.1,2.乙二胺]催化芳香酮不对称加氢反应的性能,考察了不同的碱、叔丁醇钾浓度、反应溶剂、底物/催化剂摩尔比等因素对反应活性和对映选择性的影响.在苯乙酮、叔丁醇钾、催化剂的摩尔比为1000:20:1,氢气压力为2 MPa,反应温度为30℃时,苯乙酮的转化率和α-苯乙醇的对映选择性(ee)分别达到了100%和88.5%,2'-溴苯乙醇的ee值町达97.1%.     

Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF₆] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched β-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face.