Untersuchungen zurFriedel-Crafts-Reaktion. XVI. Darstellung isomerer 2-Acyl- und 3-Acyl-4-methoxyphenole

Acylation of 4-methoxy phenol according toFriedel andCrafts, as well as the rearrangement of its esters according toFries lead always to 2-acyl-4-methoxy phenols or to their demethylated compounds. The unknown 3-acyl-4-methoxy phenols were prepared in two steps: First, the ester is acylated with the corresponding acyl chloride and SnCl₄ in nitromethane. In the second step the resulting ketoesters are hydrolysed. This is a general method. The yields ofmeta-acylphenols are between 40 and 90%. The isomeric 2-acyl-4-methoxy-phenols which were partly unknown or accessible only in low yields have also been prepared for comparative spectral studies (UV, IR, NMR, MS) ofortho- andmeta-acylphenols.

     

Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

Hf[N(SO2C8F17)2]4-catalyzed Friedel-Crafts acylation in a fluorous biphase system

In a fluorous biphase system, Hf[N(SO₂C₈F₁₇)₂]₄ complex (1 mol %) catalyzes Friedel-Crafts acylation of aromatic compounds such as anisole, toluene and chlorobenzene, and the corresponding aromatic ketones are obtained in satisfactory to high yields. The catalyst is selectively soluble in lower fluorous phase and can be easily recovered by simple phase separation. Furthermore, the catalyst can be reused without decrease of activity in most cases.     

Rare earth(III) perfluorooctanesulfonates catalyzed Friedel-Crafts alkylation in fluorous biphase system

The catalyst of rare earth(III) perfluorooctanesulfonates (RE(OSO₂C₈F₁₇)₃, RE = Sc, Y, La-Lu) were prepared from either rare earth chlorides(III) or oxides and perfluorooctanesulfonic acid. The perflates thus obtained act as novel catalysts for Friedel-Crafts alkylation in fluorous biphasic system. Perfluorohexane (C₆F₁₄), perfluoromethylcyclohexane (C₇F₁₄), perfluorotoluene (C₇F₈), perfluorooctane (C₈F₁₈), perfluorooctyl bromide (C₈F₁₇Br) and perfluorodecalin (C₁₀F₁₈, cis- and trans-mixture) can be used as fluorous solvents for this reaction. By simple separation of the fluorous phase containing only catalyst, alkylation can be repeated many times.     

New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120 °C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.     

Pyrrolopyrimidines. 5. Reaction of 6-Amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4(1H,3H)-diones with 1,3-Diketones

The reaction of 6-amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4-dione with 1,3-diketones leads to formation of predominantly pyrimido[4',5':3,4]pyrrolo[1,2-b]pyridazine-2,4(1H,3H)-diones and, to a lesser extent, pyrimido[5',4':3,4]pyrrolo[1,2-b]pyridazine-1,3(2H,4H)-diones. The ease and direction of the cyclization reaction suggests a very -electron rich pyrrole ring in the initial state, especially in the position 7.     

Synthesis,In Silico and In Vivo Toxicity Assessment of Functionalized Pyridophenanthridinones via Sequential MW-Assisted Intramolecular Friedel-Crafts Alkylation and Direct C–H Arylation

A rapid, efficient, and original synthesis of novel pyrido[3,2,1-de]phenanthridin-6-ones is reported. First, the key cinnamamide intermediates 8a–f were easily prepared from commercial substituted anilines, cinnamic acid, and 2-bromobenzylbromide in a tandem amidation and N-alkylation protocol. Then, these N-aryl-N-(2-bromobenzyl) cinnamamides 8a–f were subjected to a TFA-mediated intramolecular Friedel-Crafts alkylation followed by a Pd-catalyzed direct C–H arylation to obtain a series of potentially bioactive 4-phenyl-4,5-dihydro-6H,8H-pyrido[3,2,1-de]phenanthridin-6-one derivatives 4a–f in good yields. Finally, the toxicological profile of the prepared final compounds, including their corresponding intermediates, was explored through in silico computational methods, while the acute toxicity toward zebrafish embryos (96 hpf-LC₅₀, 50% lethal concentration) was also determined in the present study.     

有机催化吲哚碳环上的不对称Friedel⁃Crafts烷基化反应

将金鸡纳碱衍生物双功能催化剂用于有机催化羟基吲哚与靛红的不对称Friedel-Crafts反应, 筛选出最佳反应条件: 催化剂为5%(摩尔分数)6′-脱甲基奎尼丁(1b), 溶剂为四氢呋喃, 反应温度 0 ℃. 以67%~91%的产率和最高达97%的对映选择性获得了苯环上取代的羟基烷基化产品. 拓宽了该反应的催化剂类型和底物范围.     

The Carbenic Insertion into the P-P Bond

Abstract

The cycloaddition reactions on Phosphorus Chemistry¹ has allowed a new development of the three membered ring organophosphorus compounds. Starting from functionulized diphosphiranes obtained by action of carbenes on diphosphenes, we have studied their ring opening reactions leading to carbon insertion into P-P bond.     

Synthetic Utilization of α-Phosphonovinyl Anions

The α-phosphonovinyl anions, generated in situ from treatment of β-hetero-substituted vinyl-phosphonates 1a-c with LDA (or LTMP), were trapped with various electrophiles such as chlorotriorganosilanes, chlorotrimethylgermane, chlorotriorganotins, dimethyl disulfide, and halogen to afford the corresponding β-hetero-substituted α-functionalized vinylphosphonates 2–14 in good to excellent yields. The Friedel-Crafts reaction of α-(silyl) or α-(germyl)phosphonoketene dithioacetals 2, 9 or 4 with acid chlorides gave α-acylated phosphonoketene dithioacetals 15–19 in 53–91 % yields. The palladium-catalyzed cross-coupling reaction of β-ethoxy-α-(tributylstannyl)vinylphosphonate 13 with a variety of organic halides (R = acyl, allyl, aryl etc.) provided β-ethoxy-α-substituted vinylphosphonates 20–25 in good to moderate yields. The palladium-mediated cross-coupling reaction of α-(iodo)-vinyl-phosphonates 7, 14 with terminal acetylenes afforded α-alkynylated vinylphosphonates 26–29 in 69–83 % yields.