Kourosch Abbaspour Tehrani

Synthesis of Aryl(di)azinyl Ketones through Copper- and Iron-catalyzed Oxidation of the Methylene Group of Aryl(di)azinylmethanes†

Sustainable Oxidations: an oxidation method to transform aryl(di)azinylmethanes into aryl(di)azinyl ketones is described. Base metals (copper and iron) as catalysts in combination with O(2) as the oxidant are used, which makes this method sustainable. The utility of this method is illustrated by the synthesis of 6-(4-methylbenzoyl)pyridine-2-carbaldehyde, which is an intermediate in the preparation of the drug Acrivastine.

Synthesis of 3-halopyrroles

Abstract 3-Chloro-and 3-bromo-2-arylpyrroles, which are potential physiologically active compounds in agrochemistry and pharmaceutical sciences, were efficiently prepared from the corresponding 2-aryl-1-pyrrolines by α,α-dihalogenation with N-halosuccinimides and subsequent base-induced monodehydrohalogenation using sodium methoxide in methanol.

Stereochemistry of the Tadalafil Diastereoisomers: A Critical Assessment of Vibrational Circular Dichroism, Electronic Circular Dichroism, and Optical Rotatory Dispersion

The stereochemistry of all four stereoisomers of tadalafil is determined using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD) spectroscopy. By comparing experimentally obtained VCD spectra to computationally simulated ones, the absolute configuration of the enantiomeric pair (6R, 12aR)/(6S, 12aS) can be confidently assigned without prior knowledge of their relative stereochemistry. IR and NMR spectra are used to aid the assignment of the relative stereochemistry. The IR and VCD difference spectra further confirm the assignment of all stereoisomers. ECD and ORD spectra are used to investigate the complementarity of the three chiroptical techniques. VCD spectroscopy itself is found to have the ability to identify diastereoisomers, and simultaneous use of these chiroptical spectroscopic methods and NMR chemical shifts aids in increasing the reliability of stereochemistry assignment of diastereoisomers.

New synthetic approaches to 2-perfluoroalkyl-4H-pyran-4-ones

Abstract A convenient synthesis of 5-substituted 2-perfluoroalkyl-4H-pyran-4-ones by dehydration of 2,3-dihydro-3-hydroxy-6-perfluoroalkyl-4H-pyran-4-ones is described. The 6-substituted and parent 2-perfluoroalkyl-4H-pyran-4-ones have been more successfully prepared using the condensation of alkyl enol ethers, derived from β-dicarbonyl compounds, with ethyl perfluoroalkanoates.

Synthesis of 3-methoxyazetidines via an aziridine to azetidine rearrangement and theoretical rationalization of the reaction mechanism

The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.

Novel synthesis of indolizidines and quinolizidines

Abstract A very short synthesis of indolizidines, quinolizidines and some higher homologues was developed by alkylation of 2-methyl-1-pyrroline or 6-methyl-2,3,4,5-tetrahydropyridine with 1,3- or 1,4-dihaloalkanes, followed by reduction of the intermediate iminium salts, resulting in the desired 1-azabicyclo[ m . n .0]alkanes in good yields.

Synthesis of 5-alkyl-4-amino-2-(trifluoromethyl)pyridines and their transformation into trifluoromethylated 1H-pyrazolo[4,3-c]pyridines

Abstract 5-Alkyl-4-amino-2-(trifluoromethyl)pyridines were prepared in good yields starting from the corresponding pyridinols either using condensation with tosyl isocyanate or by alkylation with 2-chloroacetamide and subsequent Smiles type rearrangement. The cyclisation of diazonium salts, generated from 5-alkyl-4-amino-2-(trifluoromethyl)pyridines, afforded trifluoromethylated 1H-pyrazolo[4,3-c]pyridines.

Boron(III) bromide-induced ring contraction of 3-oxygenated piperidines to 2-(bromomethyl)pyrrolidines

Abstract 3-Methoxypiperidines were converted into 2-(bromomethyl)pyrrolidines by reaction with boron(III) bromide in dichloromethane. This reaction proceeds via an intermediate bicyclic aziridinium ion and features a rare conversion of piperidines into pyrrolidines.

Synthesis of Benzo[f]isoindole-4,9-diones

A synthesis of benzo[f]isoindole-4,9-diones 1 is presented starting from the reaction of 2,3-bis(bromomethyl)-1,4-dimethoxynaphthalene 15 with primary amines affording 2,3-bis(aminomethyl)-1,4-dimethoxynaphthalenes 14, which could be converted by CAN-mediated oxidation in one step to benzo[f]isoindole-4,9-diones 1. An alternative synthesis of benzo[f]isoindole-4,9-diones 1 starts from 2,3-bis(bromomethyl)-1,4-naphthoquinone 9 via 2,3-dihydrobenzo[f]isoindoles 10 which spontaneously oxidize.

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen.

Summary The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP–MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.