Királis, fluoros fázisban oldható homogén katalizátor prekurzor ligandumok szintézise és alkalmazása = Synthesis and application of chiral fluorous phase soluble ligands for catalysts

Mitsunobu-reakcióban pro-nukleofilként viselkedő fluoros vegyületek [(CF3)3COH, (CF3)2C(OH)2, perfluoropinakol, CF3SO2NH2] és perfluoralkil-propanolok [CnF2n+1(CH2)3OH] reakciójával fluorofil O- és N-alkilezett származékokat állítottunk elő jó termeléssel. Kidolgoztuk egy új típusú fluorofil szerkezeti részlet beépítését [(CF3)3CO], ami nagyfokú kémiai stabilitással rendelkezik és nagymértékű fluorofilitást biztosít. Preparatív méretekben (50-500 g) kidolgoztuk fluorofil reagensek szintézisét (éterek, aminok, jódhidrinek, alkoholok, alkének) egyszerű kiindulási anyagokból. A termékek tiszta állapotban történő kinyerésére fluoros extrakciót, szilárd fluoros - szerves folyadék szűrést és vízgőzdesztillációt alkalmaztunk. Fluoros propének esetében piridin segítségével oldószergőz-desztillációval sikerült a tisztítást elvégezni. Előállítottuk az optikailag aktív feniletilamin fluoros származékait. A szabad bázisok és hidrokloridjaik oldhatóságát tíz különböző oldószerben vizsgáltuk. Egy új módszert alkalmaztunk egy szulfoxid-dikarbonsav fluoros királis bázissal történő reszolválására vizes közegben. Az előállított molekulák szelektív fizikai tulajdonságait vizsgáltuk (olvadáspont, forráspont, fluoros megoszlási hányados) és kvalitatív következtetéseket vontunk le a szerkezet és a makroszkópikus tulajdonságok között. | The Mitsunobu reaction of pro-nucleophiles (CF3)3COH, (CF3)2C(OH)2, perfluoropinacol and CF3SO2NH2 with CnF2n+1(CH2)3OH alcohols resulted in the high yield formation of the appropriate fluorophilic O- and N-alkylated products. The novel bulky fluorous ponytail (CF3)3CO displays high acidic stability and increases fluorousness almost as much as the classical straight-chain C8F17(CH2)3 ponytail. Fluorophilic reagents (ethers, amines, iodohydrines, alcohols, alkenes) were prepared in preparative scale in good yields starting from commercially available chemicals. To achieve ideal separations, products were transferred to orthogonal phases relative to the other reaction components using fluorous extraction, fluorous solid?organic liquid filtration, or steam-distillation. Fluorous propenes were effectively isolated by co-distillation with pyridine. Fluorous chiral amine derivatives of phenylethylamin were obtained. The solubility patterns of these novel chiral amines and their hydrochlorides were qualitatively described for a broad spectrum of solvents. A novel method for the resolution of enantiomers was disclosed, which involves the use a half-equivalent of the selected resolving agent in water. Selected physical properties including melting and boiling point, together with fluorous partition coefficients of compounds were determined and the figures obtained were qualitatively analyzed

Organic & Biomolecular Chemistry PAPER Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-ones †

The palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-one with (het)arylboronic acids allow easy access to (het)aryl and vinyl derivatives of this bicycle in good to excellent yields, even from chloro derivatives. The sequence of reactivity of the halogen in the different positions of the ring system was also investigated. 6-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one could be prepared by thermal cyclization of isopropylidene (6-phenylpyrid-2-ylamino)methylenemalonate, together with a small amount of 7-phenyl-1,4-dihydro-1,8-naphthyridin-4-one. The 4H-pyrido[1,2-a]pyrimidin-4-one scaffold is a privileged structure 1 in medicinal chemistry, as the physical properties of its derivatives usually meet the criteria of the "rule of five" for the development of orally active drugs. 2 The derivatives display diverse biological activities, and some outstanding representatives have been introduced into human therapy as analgesic, antiinflammatory, antiallergic or antipsychotic agents. 3 Risperidone, a member of this class, was one of the drugs most widely prescribed worldwide in 2007. 4 Paliperidone, 5 the main metabolite of risperidone, was recently introduced into human therapy as an oral atypical antipsychotic for the treatment of bipolar disorders. Its palmitate ester prodrug is currently under evaluation by the FDA as a monthly injection for the treatment of schizophrenia. 6 4H-Pyrido[1,2-a]pyrimidin-4-ones are usually synthesized from 2-aminopyridines, and functionalization of this bicyclic ring system has not been explored, expect in positions 2 and 3. 7 Direct synthesis from 2-aminopyridines is sometimes accompanied by poor yields. For example, the potent glycogen synthase kinase 3b inhibitor 2-(4-pyridyl)-4H-pyrido[1,2-a]pyrimidin-4-ones could be prepared in yields of only 10-28% in the reactions of 2-aminopyridines and ethyl 3-(4-pyridyl)-3-oxopropionate in PPA at 140-150 • C for 12 h