Regioselective assembly of 3,4-dihydroisoquinoline derivatives

A facile two-step sequence (9→10→1) of regioselective assembly of 3,4-dihydroisoquinoline derivatives 1 is reported. The halogen derivatives provide opportunity for Suzuki, Buchwald, and related coupling reactions useful for expanding the scaffold and lead optimization in drug discovery.     

芴2,7位取代的9,9’-二芳基螺芴类化合物的合成及性能

设计并合成了一系列以三苯胺为核,芴衍生物为外围基团的有机蓝光小分子,该合成通过Suzuki反应在9-芳基芴的2位和(或)7位引入相同或不同取代基作为模块,并利用Friedel-Crafts反应将4-甲基三苯胺与这一系列模块结合.用NMR,MS和元素分析进行结构表征.荧光测试结果表明该类化合物溶液的荧光发射波长范围在442～466 nm之间,属蓝光发射.电化学测试显示该类材料的HOMO能级位于-5.15～-5.19 eV之间.差示扫描量热仪与热重分析得出化合物的玻璃化转变温度在166℃以上,热分解温度高于398℃,表明该类材料具有良好的热稳定性.     

Facile Diastereoselective Synthesis of Carbohydrate-Based Thiochromans

An efficient and novel diastereoselective thiochroman synthesis using the carbohydrate chiral pool via intramolecular Friedel-Crafts alkylation is presented. The scope and limitations of the method are investigated.     

Synthesis and some transformations based on 8-chloro-3-methylxanthine

The reactions of 8-chloro-7-(β-chloro-γ-hydroxypropyl)-3-methylxanthine with primary and secondary amines have been studied. A method has been developed for obtaining derivatives of 7-hydroxy-1-methyl-6,7,8,9-tetrahydro-3H-pyrimido[2,1-f]-xanthine. The structures of the compounds synthesized have been confirmed by IR and PMR spectroscopy. Zaporozh'e Medical Institute. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 626–629, September–October, 1980.     

Synthesis of new 8-arylisoquinoline derivatives by application of palladium-catalyzed Suzuki cross-coupling reactions

New 8-(het)aryltetrahydroisoquinolines (10-14), 8-aryltetrahydroisoquinolin-4-ols (15,16), and 8-phenylisoquinolin-4-ol (17), flexible analogues of aporphine, were synthesized in good yields using palladium-catalyzed Suzuki cross-coupling reactions from 8-bromotetrahydroisoquinolin-4-one (6) as a common intermediate. We also describe the synthesis of this novel intermediate through an easy and efficient method, which involved intramolecular Friedel-Crafts cyclization.     

Three-component synthesis of 3,4-dihydroisoquinoline derivatives

A simple and convenient method for the synthesis of 1-substituted 3,3-dimethyl-3,4-dihydroisoquinolines was developed. The method is based on the [2+2+2] cyclization of alkyl- or alkoxybenzenes with isobutyraldehyde and nitriles.     

11,11,12,12-四氰基-2-对甲基苯基-9,10-蒽醌二甲烷的合成及其光谱性能

以邻苯二甲酸酐和对溴甲苯为原料,经Friedel-Crafts酰基化、浓硫酸催化、Suzuki偶联及Knoevenagel缩合合成了一种新型的四氰基-9,10-蒽醌二甲烷衍生物——11,11,12,12-四氰基-2-对甲基苯基-9,10-蒽醌二甲烷(5),其结构经1H NMR,ESI-MS和元素分析表征。UV-Vis和荧光光谱研究表明,5在249 nm,332 nm和426nm有较强吸收;在375 nm激发波长激发下,5的最大发射波长在595 nm。     

Stereochemical course of the reductive spiroannulations of N-Boc and N-benzyl 2-cyanopiperidines

The stereochemical outcome of spiroannulations of N-protected 2-lithiopiperidines (generated by lithium di-tert-butyl biphenylide (LiDBB) mediated reductive lithiation of 2-cyanopiperidines) was investigated using deuterium labeled side-chains containing phosphate leaving groups. High stereoselectivity was observed when benzyl (Bn) protected 2-cyanopiperidines were employed, while tert-butoxycarbonyl (Boc) protected 2-cyanopiperidines afforded lower selectivity. Models are proposed to rationalize the results of this study.     

Synthesis of N-alkoxy-substituted 2H-benzimidazoles

Treatment of 2-nitro-N-(2-methyl-1-propen-1-yl)benzenamines with potassium tert-butoxide in tert-butanol followed by the addition of an electrophile affords N-alkoxy-2H-benzimidazoles. Electrophiles including methyl iodide, allylic bromides, propargylic bromides, benzyl bromide, and acetyl chloride gave good to excellent yields of product while 1-iodo- and 2-iodo-butane afforded very low yields.     

8-epi-Liphagal的合成研究

四环杂萜类天然产物Liphagal含有新奇的[6-7-5-6]四环骨架, 是磷酸肌醇3-激酶(PI3K)的有效抑制剂之一, 可以选择性抑制细胞增殖和促进细胞死亡, 在治疗炎症、免疫紊乱、癌症以及心血管疾病中有潜在的医用价值. 从廉价的2,4,5-三甲氧基苯甲醛出发, 通过Wittig反应、Cu催化的环化反应、选择性氢化、分子内Friedel-Crafts反应, 以直线步骤最长7步, 8.72%的总收率实现了8-epi-Liphagal高级中间体10的合成.     

Three-component synthesis and antibacterial evaluation of some novel 1,2-dihydroisoquinoline derivatives

Isoquinoline reacts with dialkyl acetylenedicarboxylates in the presence of kojic acid or8-hydroxyquinoline to generate 1,2-dihydroisoquinoline derivatives. The simplicity, mild reaction conditions and high yields of products make it an interesting process compared to other approaches. The compounds have been analyzed for antibacterial activity against Gram negative and Gram positive bacteria. The results indicated that 1,2-dihydroisoquinolines derived from kojic acid are effective against all of the studied bacteria especially against Bacillus subtilis, while the products obtained from8-hydroxyquinoline are active only against Gram positive bacteria.     

Synthesis of novel racemic 3,4-dihydroferroceno[c]pyridines via the Ritter reaction

A new approach for the synthesis of functionalized racemic 3,4-dihydroferroceno[c]pyridines via the Ritter reaction of 2-methyl-1-ferrocenylpropan-1-ol with nitriles in the presence of methansulfonic acid was developed. The scope and limitations of the reaction were evaluated. Selected racemic 3,4-dihydroferroceno[c]pyridines were successfully separated by preparative HPLC on a Chiralcel OD-H column. The absolute configuration of the enantiomers was determined by X-ray crystal structure analysis.     

Selective protodeboronation: synthesis of 4-methyl-2-thiopheneboronic anhydride and demonstration of its utility in Suzuki-Miyaura reactions

An efficient synthesis of 4-methyl-2-thiopheneboronic anhydride is reported. Regioselective lithiation of 3-methylthiophene followed by reaction with triisopropylborate and hydrolysis provides a 92:8 ratio of 4-methyl-2-thiopheneboronic acid (1) and regioisomeric 2-methyl-3-thiopheneboronic acid (3). The undesired regioisomer is selectively protodeboronated with concentrated acid to provide only the desired 4-methyl-2-thiopheneboronic acid (1). The title compound is isolated by dehydration/crystallization and employed in several Suzuki-Miyaura reactions.     

Regiospecific substitution of the carbon-boron bond of tris(4-trimethylsilylfuran-3-yl)boroxine and tris(4-methylfuran-3-yl)boroxine. Model approaches towards sesquiterpenoid furanoeudesmanes

Furan-containing compounds occur abundantly in nature. Among them, the sesquiterpenoid furanoeudesmanes are particularly interesting due to their allergenic, plant-growth inhibiting, antibacterial as well as antitumor properties. Recently an organoboron protocol has been developed in our laboratory for the preparation of regiospecific-substituted furans. By utilizing such methodology, two common intermediates 1 and 2 that may lead to the synthesis of naturally occurring tubipofuran (3) furanoeudesm-4-ene (4) and furanoeudesma-1,4-dien-6-one (5) were obtained.     

Synthesis of SMP-797: a new potent ACAT inhibitor

A potent ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor SMP-797 was effectively synthesized by the urea formation of 3-amino-4-aryl-1,8-naphthyridin-2(1H)-one and 4-amino-2,6-diisopropylamine. The synthesis of the former compound involved the Suzuki coupling reaction as a key step, and the latter was prepared by the 4-selective nitration of 2,6-diisopropylaniline using 2,3,5,6-tetrabromo-4-methyl-4-nitro-2,5-cyclohexadienone.     

Synthesis of 1-indanones by intramolecular Friedel-Crafts reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3

Intramolecular Friedel-Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)₃ at 250 °C to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation to good yields.     

Allylboration and cyclization of 3,4-dihydroisoquinoline derivatives. Synthesis of the benzopyrrocoline system

A novel approach to hexahydropyrrolo[2,1-alisoquinolines (hexahydrobe nzo[glpyrro-colines) based on the allylboration of 3,4-dihydroisoquinolines followed by closure of the pyrrolidine ring through the hydroboration — oxidation — intramolecularN-alkylation sequence was developed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 935–937, April, 1996.     

Synthesis of benzimidazoles from o-phenylenediamines and DMF derivatives in the presence of PhSiH3

A simple approach to preparation of benzimidazoles from o-phenylenediamines and DMF derivatives, only employing PhSiH₃ as promoter without any other additives, was reported. This route provided moderate to high yields with a broad substrate scope. A plausible mechanism for the reaction is proposed based on the spectroscopic characterization (e.g., HRMS and ¹H NMR) of the reaction mixture.     

Synthesis of 3,4-diarylsubstituted hexahydro-1H-indoles

Efficient syntheses of 3,4-diarylsubstituted hexahydro-1H-indoles in good yields with excellent diastereoselectivities were achieved with a two-step protocol comprising an allylic cation mediated nucleophilic addition and an intramolecular cyclization reaction. The N-aryl sulfonyl protecting groups of cyclization products were readily removed to furnish free amines with retention of halogen substitutions and CC double bonds.     

The First Synthesis of Functionalized Oxacalix[4]crown Ethers

O-alkylation and cyclization of 25,27-dihydroxy-4,6,16,18-tetranitro-oxacalix[4]arene were performed with mono- and bifunctional alkylating agents under basic conditions. In this way several 1,3-alt oxacalix[4]crown-4, 5 and 6 ethers were synthesized and characterized