Practical Synthetic Method Research Articles

ChemInform Abstract: Catalytic Asymmetric Synthesis of Stable Oxetenes via Lewis Acid Promoted [2 + 2] Cycloaddition.

A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity.

A practical and enantioselective synthesis of tapentadol

A practical and enantioselective synthetic method for tapentadol has been described. Starting from inexpensive and readily available (E)-3-(3-(benzyloxy)phenyl)acrylic acid, tapentadol was prepared in seven steps (44% overall yield and 99.9% de) in more than 100g batches, without any chromatographic purification. An Evans’ chiral auxiliary based conjugate addition and alkylation were used as the key steps.

ChemInform Abstract: Palladium‐Catalyzed Cross‐Coupling of PhSeSnBu3 with Aryl and Alkyl Halides in Ionic Liquids: A Practical Synthetic Method of Diorganyl Selenides.

AbstractThe Pd‐catalyzed reaction of phenylselenylstannane (II) with a wide variety of aromatic and aliphatic iodides and bromides proceeds smoothly in a room temperature ionic liquid to give the corresponding phenyl organyl selenides in good yields.

A Practical Synthetic Method for 7-ATCA

7-ATCA is a major intermediate of Cefditoren pivoxil. Literatures reported 7-ATCA was generally synthesized by the method of sheer chemistry or combinative method of biochemistry and chemistry. Considering reduction of environmental pollution, the combinative method has more preference. We optimized the amount of sodium iodide and 4-methyl-5-thiazolaldehyde in Wittig reaction and the sorts of reagents for removing C-4 deprotection group. 7-ATCA was obtained after penicillin acylase hydrolysis of C-7 protection group in a mild condition. The structure of 7-ATCA was characterized by 1H NMR and the total yield was up to 55%.

A Practical Synthetic Method of O-(2-(Pyrazol-1-yl)pyridin-5-yl)methylhydroxylamine as a Component of Modithromycin

A practical synthesis of O-(2-(pyrazol-1-yl)pyridin-5-yl)methylhydroxylamine was achieved from the inexpensive raw materials, 2-chloro-5-chloromethylpyridine, pyrazole, and acetone oxime, using common reagents such as aq NaOH and sulfuric acid.

Practical synthesis of aromatic nitriles via gallium-catalysed electrophilic cyanation of aromatic C–H bonds

A gallium-catalysed, direct cyanation reaction of aromatic and heteroaromatic C-H bonds with cyanogen bromide was developed as a practical synthetic method for the preparation of aromatic nitriles.

Carbene Transfer Reactivities of Nickel(II)–N-Heterocyclic Carbene Complexes and Their Applications in the Synthesis of Metal–NHC Complexes

We describe a new synthetic procedure for transition-metal N-heterocyclic carbene complexes (NHCs). A number of Pd(II), Pt(II), Co(III), and Ru(II) complexes containing functionalized NHCs have been obtained in good to excellent yields using NiII–NHC complexes as carbene transfer reagents. NiII–NHC complexes are easily prepared from the direct reactions of the corresponding imidazolium salts with commercially available Raney nickel powder. The byproduct of transmetalation reactions, NiCl2, can be easily removed by simple filtration. This study offers a new, economical, and practical synthetic method for metal–NHC complexes.

Catalytic Asymmetric Synthesis of Stable Oxetenes via Lewis Acid-Promoted [2 + 2] Cycloaddition

A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity.

The Use of Fluoride as a Leaving Group: SN2′ Displacement of a CF Bond on 3,3‐Difluoropropenes with Organolithium Reagents To Give Direct Access to Monofluoroalkenes

Lithium is the key to activate the nucleofuge ability of fluoride in the title transformation (see scheme). This simple and straightforward approach not only provides a practical synthetic method for the preparation of monofluoroalkenes, an important fluorinated motif, but also demonstrates the ability of fluoride to act as a competent leaving group in nucleophilic substitution reactions.

Process Research on the Asymmetric Hydrogenation of a Benzophenone for Developing the Manufacturing Process of the Squalene Synthase Inhibitor TAK-475

A practical synthetic method for the synthesis of the chiral benzhydrol 8, which is the key intermediate of the squalene synthase inhibitor TAK-475 (1), has been developed. The method, via asymmetric hydrogenation of the benzophenone 7, employed Noyori’s ruthenium precatalyst of the type [RuCl2(diphosphine)(diamine)]. We focused on tuning of the chiral diphosphine, and have discovered a novel ligand, DADMP-BINAP (18c), for the catalyst that has allowed reduction of the operating pressure in the asymmetric hydrogenation. The precatalyst containing 18c performed effectively at low hydrogen pressure (<1 MPa) with sufficient enantioselectivity, and the result enabled us to successfully obtain enantiomerically pure 8 on a multikilogram scale.

ChemInform Abstract: Development of a Practical Synthetic Method for N‐tert‐Butoxycarbonyl α‐Ketimino Esters.

AbstractAn operationally simple procedure for the synthesis of the title compounds (III) is presented.

ChemInform Abstract: Development of Practical Synthetic Method Toward Mechanistic Elucidation of Biologically Active Natural Products

AbstractReview: ca. 50 refs.

Synthesis of Functionalized 2-Aminohydropyridines and 2-Pyridinones via Domino Reactions of Arylamines, Methyl Propiolate, Aromatic Aldehydes, and Substituted Acetonitriles

An efficient and practical synthetic method for the functionalized 2-amino hydropyridines and 2-pyridinones was successfully developed via the domino reactions of arylamines, methyl propiolate, aromatic aldehydes and the substituted acetonitriles with triethylamine as base catalyst. Reactions involving malononitrile and cyanoacetamide gave exclusively the 2-aminohydropyridines. On the other hand ethyl cyanoacetate resulted in the 2-pyridinones as main products.

Development of a Practical Synthetic Method for N-tert-Butoxycarbonyl α-Ketimino Esters

Abstract Despite the potential synthetic utility of N-Boc α-ketimino esters as prochiral ketimines to give chiral α-tertiary amines, there has been no general method to access these molecules in a practical fashion. We report herein a procedure for the one-step synthesis of N-Boc α-ketimino esters starting from the corresponding α-keto esters.

Palladium-catalyzed cross-coupling of PhSeSnBu3 with aryl and alkyl halides in ionic liquids: a practical synthetic method of diorganyl selenides

Palladium-catalyzed cross-coupling reactions of phenyl tributylstannyl selenide with aryl and alkyl halides can proceed smoothly in room temperature ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]), to give the corresponding diorganyl selenides in good to high yields. The coupling reaction run in [bmim][PF6] has the advantages of rate acceleration and increase of yield in contrast to the reaction run in toluene. Our system not only avoids the use of easily volatile toluene as a solvent but also solves the basic problem of palladium catalyst reuse.

Facile aerobic photo-oxidative synthesis of α-diketones from alkynes

We report a useful method for facile aerobic photo-oxidative synthesis of α-diketones from alkynes with MgBr 2·OEt 2. This procedure provides a practical synthetic method of α-diketones using easily handled bromine sources, harmless visible light, and molecular oxygen as terminal oxidant.

Facile Benzo-Ring Construction via Palladium-Catalyzed Functionalization of Unactivated sp3 C−H Bonds under Mild Reaction Conditions

A practical synthetic method for the annulation of benzo-rings by the intramolecular coupling of an aryl iodide and a methylene C-H bond is described. The palladium-catalyzed C-H functionalization is directed by an aminoquinoline carboxamide group, which can be easily installed and removed. High yields and broad substrate scope were achieved. An additive of ortho-phenyl benzoic acid, identified from a systematic screening, functions as a critical ligand for the catalytic process under mild condition, even at near room temperature.

ChemInform Abstract: A Practical Synthetic Method for α- and β-Glycosyloxyacetic Acids.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of 1,2-disubstituted benzimidazoles, 2-substituted benzimidazoles and 2-substituted benzothiazoles in SDS micelles

A practical and convenient synthetic method has been developed for the facile synthesis of 1,2-disubstituted benzimidazoles, 2-substituted benzimidazoles and 2-substituted benzothiazoles. The method described has the benefits of operational simplicity, excellent yields, and high chemoselectivity.

Efficient Synthesis of Pyrimido[1,2-c] [1,3]benzothiazin-6-imines and Related Tricyclic Heterocycles by SNAr-Type C−S, C−N, or C−O Bond Formation with Heterocumulenes

A simple and practical synthetic method of pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic heterocycles has been developed. Treatment of 2-(2-haloaryl)tetrahydropyrimidines with NaH and a heterocumulene such as carbon disulfide, isothiocyanates, and isocyanates in DMF provides the desired cyclization products through a regioselective S(N)Ar-type reaction. This method provides direct access to PD 404182 and related compounds.