金催化炔基膦酸酯水合反应合成β-羰基膦酸酯

β-羰基膦酸酯是一类重要的有机化合物和反应中间体,在有机合成及药物化学中发挥着重要的作用.提供了一种高原子经济性、高选择性、温和的炔基膦酸酯水合反应体系.实验结果表明:在阳离子金催化剂(2.5 mol%)的催化作用下,以1,2-二氯乙烷(1 m L)为溶剂,室温下炔基膦酸酯(1 mmol)与水(3 mmol)发生水合反应,高收率、高区域选择性地得到β-羰基膦酸酯化合物(收率≥92%).该方法具有底物适用范围广、反应条件温和、环境友好等优点,为含β-羰基膦酸酯结构单元的天然产物及复杂药物分子的合成提供了一种新途径.     

铑(II)催化重氮苄基膦酸酯与芳香亚胺的氮杂环丙烷化反应

铑(II)催化重氮苄基膦酸酯与芳香亚胺反应, 一步合成氮杂环丙烷-2-膦酸酯. 该方法立体定向地得到唯一的反式构型产物, 反应历程是重氮化合物先与亚胺形成叶立德中间体, 然后发生自身环丙烷化反应.     

3-取代芳基-2-吲哚基膦酸酯的合成

本文根据Fischer吲哚合成法制备了一系列的3-取代芳基-2-吲哚基膦酸酯. 盐酸苯肼与o,o-二异丙基-4-氯-苯乙酰基膦酸酯在无水酒精中反应, O,O-二异丙基-(4'-氯苯-3H-吲哚-2-膦酸酯能被分离出来, 而且它的异构化最终产物能被观察到.     

有机磷化合物研究XVIII α-砜基膦酸酯的合成和反应

本文报道α-砜基碳阴离子和磷酰氯的反应,提供了合成α-砜基膦酸酯和α,β-不饱和砜的新方法,此方法具有原料易得、反应步骤少、得率较高等优点.还讨论了α-芳砜基膦酸酯的质谱.     

微波法合成烯基膦酸酯类化合物

以β-硝基芳基乙烯和亚磷酸三乙酯为原料,二氯甲烷为溶剂,利用微波法合成了一系列烯基膦酸酯类化合物,其结构经<'1>H NMR,<'13>C NMR和HR-MS确证.     

α-芳基烯基膦酸酯的合成研究进展

α-芳基烯基膦酸酯是一类重要的有机磷化合物,并且是合成其它有机磷分子的重要中间体.重点综述了过渡金属催化合成α-芳基烯基膦酸酯的进展,如磷氢化反应、C—C偶联反应和C—P偶联反应等,其它非金属催化条件下的几类合成方法也进行了概述.对α-芳基烯基膦酸酯的有机转化及在膦胺霉素衍生物合成中的应用也进行了探讨.     

通过Michaelis-Arbuzov重排合成新型

α-溴代-叔丁基甲基酮和3-取代2,2-二甲基环丙烷羧基氯化物与亚磷酸酯反应,生成膦酸酯,并描述了膦酸酯的溴化反应.     

乙烯基膦酸酯的钯催化芳基化和烯基化反应

本文报道乙烯基膦酸酯在钯催化下的芳基化和烯基化反应,乙烯基膦酸酯与芳基溴化合物在钯催化下反应,可顺利地生成相应的E式2-芳基取代乙烯基膦酸酯(6,7).操作简便,反应条件温和,产率中平,是合成2-芳基取代乙烯基膦酸酯较好的方法.测定了不同取代芳基乙烯基膦酸二乙酯的^31P NMRδ值,它们与Hammett取代基常数σ之间有较好的线性关系.乙烯基膦酸酯亦能与烯基溴化合物反应,生成相应的取代1,3-二烯基膦酸酯(10),但反应时间较长,产率较低,由NMR推定了6,7和10的构型。     

光学活性α-羟基磷酸酯的合成

扼要综述了近年来关于光学活性α一羟基膦酸酯的新合成方法,介绍了有关的手性试剂和不对称反应。关键词##4光学活性;;α-羟基膦酸酯;;不对称合成     

顺[1-溴-2-羟基-2-(对-甲氧基苯基)乙基]膦酸二异丙酯的羟基反应性能的研究

研究了顺[1-溴-2-羟基-2-(对-甲氧基苯基)乙基]膦酸二异丙酯羟基的反应性能。由于膦酸酯基和电负性的溴原子的吸电子作用,羟基氧原子周围的电子云密度降低．从而增强了羟基上质子的酸性并减弱了碱性条件下相应的烷氧基负离子的亲核能力,因而得到了有关羟基与酚进行Mitsunobu脱水反应和酯化反应的特殊反应性能。同时,由于氢键的作用和膦酸酯基团的空问障碍作用,羟基与酰氯的反应活性较低。     

Dianion of sulfinylacetone as a synthetic equivalent of beta-enolate of propionic acid: a novel synthesis of carboxylic acids from alkyl halides with three-carbon elongation

The reaction of the dianion of phenylsulfinylacetone with alkyl halides afforded beta-keto sulfoxides, which were first chlorinated with hexachloroethane and then treated successively with KH and t-BuLi to give carboxylic acids in three-steps in moderate overall yields from the alkyl halides. This procedure affords a good method for a synthesis of carboxylic acids from alkyl halides with three-carbon elongation.     

Regioselective [3+3] Cyclization of 1,3‐Bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐Trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones: New and Convenient Synthesis of Functionalized 5‐Alkyl‐3‐(trifluoromethyl)phenols

Functionalized 5‐alkyl‐3‐(trifluoromethyl)phenols were prepared by formal [3+3] cyclization of 1,3‐bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones derived from 1,1,1‐trifluoroalkane‐2,4‐diones. The latter were prepared by condensation of the dianion of 1,1,1‐trifluoropentane‐2,4‐dione with alkyl halides.     

Reactivities of dianions of pyridyl phenyl ketones

Substituted pyridylphenylcarbinols are formed in the reaction of the dianions of isomeric pyridyl phenyl ketones with alkyl halides, aldehydes, and benzonitrile. The reaction of the dianion of 3-pyridyl phenyl ketone with benzophenone, in contrast to the analogous reaction of the dianion of 2-pyridyl phenyl ketone, gives 5-benzoyl-2-diphenylhydroxymethyl-1,2-dihydropyridine. It is assumed that the observed reaction includes one-electron transfer and the formation of two anion radicals. Recombination of the anion radical of 3-pyridyl phenyl ketone leads to 5,5′-dibenzoyl-2,2′-di(1,2-dihydropyridyl).     

Synthesis of α-silylcarboxylic acids

New α-silylacetic acids have been prepared following a general and convenient procedure of a one-pot reaction between trimethylsilylacetate and different chlorosilanes. New derivatives of diphenyl(methyl)silylacetic acid were prepared by a direct alkylation of its dianion with benzyl-, allyl-, and alkyl halides and trimethylchlorogermane to afford new α-silylcarboxylic acids.     

The synthesis of diene and of vinyl copolymers containing predetermined quantities of polynuclear hydrocarbon or heterocyclic adducts—VI. Copolymers of butadiene,acenaphthylene or phenanthrene,and a linking agent

Reactions of tetrahydrofuran solutions of butadiene and acenaphthylene with alkali metal produce dianionic species which give quantitative yields of copolymers when subsequently titrated with alkyl dibromides. These polymers, however, crosslink on standing; this has been correlated with the presence of a proportion of 1,5-dihydroacenaphthylene adduct in the product.Similar reactions involving phenanthrene are not quantitative and yield materials containing only a small proportion of the phenanthrene added. The low efficiency has been attributed to the low electron affinity of phenanthrene and to the ability of its dianion to react with alkyl halides by electron transfer rather than metathetically.     

Investigations on 2,3'-Biquinolyls. 12. Alkylation and Arylation of 2,3'-Biquinolyl Dianion with Organometallic Compounds. New Type of Reaction for Dianions of Aromatic Compounds

2,3'-Biquinolyl dianion reacts with organolithium and organomagnesium compounds with the formation, after treatment of the reaction mixture with water, of 2'-alkyl(aryl)-1',2'-dihydro-2,3'-biquinolyls, and, after treatment of the reaction mixture with alkyl halides, of 1'-alkyl-2'-alkyl(aryl)-1',2'-dihydro-2,3'-biquinolyls. The reaction includes attack of the nucleophilic reagent with an electron transfer to a molecule of solvent.     

The alkylation of hantzsch 1,4-dihydropyridines

The reaction of carbanions derived from Hantzsch 1,4-dihydropyridines with alkyl halides was studied and methods for mono- and di-alkylation were devised.     

Primary alkyl fluorides as regioselective alkylating reagents of lithium arene dianions. Easy prediction of regioselectivity by MO calculations on the dianion

Lithium arene dianions derived of polycyclic aromatic hydrocarbons, such as naphthalene, anthracene, phenanthrene, fluoranthene, pyrene, chrysene and binaphtyl react cleanly with n-alkylfluorides to afford regiochemically controlled alkylated dihydroarenes after hydrolysis. These arene dianions can be easily prepared by simple treatment of the arene with lithium in THP. Unlike simple radical coupling, the alkylation of these species with alkyl fluorides apparently goes through a S_N2 transition state, despite the inertness of alkyl fluorides to undergo nucleophilic substitution. It is also atypical for reduced arenes, which tend to give ET reactions with other alkyl halides. Prediction of the regiochemistry was easily conducted by means of MO calculations (PM3) on the dianion, and in all cases were consistent with the experimental.     

Copper(I)-catalyzed boryl substitution of unactivated alkyl halides

Borylation of alkyl halides with diboron proceeded in the presence of a copper(I)/Xantphos catalyst and a stoichiometric amount of K(O-t-Bu) base. The boryl substitution proceeded with normal and secondary alkyl chlorides, bromides, and iodides, but alkyl sulfonates did not react. Menthyl halides afforded the corresponding borylation product with excellent diastereoselectivity, whereas (R)-2-bromo-5-phenylpentane gave a racemic product. Reaction with cyclopropylmethyl bromide resulted in ring-opening products, suggesting the reaction involves a radical pathway.     

A new approach for generic screening and quantitation of potential genotoxic alkylation compounds by pre-column derivatization and LC-MS/MS analysis

A generic LC-MS/MS method was developed for the analysis of potentially genotoxic alkyl halides. A broad selection of alkyl halides were derivatized using 4-dimethylaminopyridine in acetonitrile. The reaction conditions for derivatization, i.e., solvent, reaction time, temperature and concentration of alkyl halide, active pharmaceutical ingredient (API), and reagent, were optimized for sensitivity and robustness. The interference of the matrix and the API and the presence of water on the derivatization reaction were investigated for a model drug product (paracetamol/caffeine tablets). Hydrophilic interaction liquid chromatography was used to allow a quantitative determination of the derivatives by tandem mass spectrometry. The derivatization reaction was shown to be selective for alkyl halides, although some reactivity was also observed for an aromatic sulfonate, which is also genotoxic. Even though differences in reaction efficiencies have been observed, the enhanced sensitivity obtained by the derivatization allows the majority of the alkyl halides to be detected by MS/MS at relevant levels for genotoxic impurity evaluation, i.e., 10 mg kg(-1). Another key advantage is that for the majority of derivatives, reagent-related fragments are produced, which allows low-level screening for alkyl halides. Highly specific MS detection can be performed using neutral loss and precursor ion scan experiments. The applicability of a generic screening method will make the genotox evaluation less dependent on the quality of assessments based on predictions only, and it will provide essential information during the development of new chemical entities. In addition to screening, target analysis in the low milligrams per kilogram range can be performed. A similar response of the derivatized compounds was obtained in the range of 1-100 mg kg(-1) with a reproducibility better than 10%, which is sufficient for the determination of alkyl halides in APIs and drug products.