Letters in Organic Chemistry - Volume 8, Issue 4, 2011

An unusual synthesis of isoxazoles from α,β-unsaturated ketoximes is reported. Using very inexpensive reagents, isoxazoles are isolated in good yields. Notably, a mixture of E and Z oxime isomers is employed. Initial studies indicate the oxidative cyclization reaction does not proceed via radical route; a copper insertion/elimation route is proposed.

A new synthetic approach for the antiglaucoma agent, travoprost (1) has been developed in four steps from key intermediate (2). Key transformations include Horner-Wadsworth-Emmons reaction and separation of diastereomers to obtain (±) travoprost (1) and its analogs.

The differences of (R)-glycidyl butyrate synthesis via hydrolytic kinetic resolution of glycidyl butyrate directly or regioselective opening epichlorohydrin as key steps by using Jacobsen's hydrotic kinetic resolution are compared. In the view of separation problem, it is hard to get the pure (R)-glycidyl butyrate by kinetic resolution of glycidyl butyrate directly. Via kinetic resolution of epichlorohydrin, treatment with butyric acid in the presence of CrCl3 and then epoxidation with NaOH, the total yield of 38.5% and optical purity of 99% are obtained.

Aculeatins A and B, two naturally occurring bioactive spiroacetals, have been synthesized efficiently in stereoselective manner starting from 1-tetradecanal. The synthetic strategy involves Maruoka enantioselective allylation, diastereoselective iodine-induced electrophilic cyclization, alkylation of a chiral aldehyde and oxidative spirocyclization as the important steps.

N-heterocyclic norbornene Dicarboximides were synthesized by reacting the exo-norbornene-5,6-dicarboxylic anhydride with 2-, 3-, and 4-aminopyridine. The amides resulting from 3 and 4-aminopyridine derivatives were converted into the corresponding betaines via Menshutkin reaction using ethyl-bromoacetate. The chemical structures of the obtained products were confirmed by FT-IR and 1H and 13C NMR spectroscopy, EA and MS as well as by calculation of 1H and 13C NMR chemical shifts using the GIAO method (PW91/6-311G++ (3df, 3pd) approximation by GAUSSIAN and PW91/IGLO-III approximation by deMon2k).

The convergent total synthesis of tarennane has been accomplished in six steps starting from commercially available phloroglucinol and guaiacol; the key step of the synthesis relies on a highly regioselective Heck reaction applying iodophenol and PdCl2(PPh3)2.

An environmentally benign Biginelli reaction for the large-scale preparation of substituted 3,4- dihydropyrimidin-2(1H)-ones using protic acids as a catalyst has been achieved. These mechanochemical reactions proceed efficiently in the absence of organic solvent, with the assistance of infrared lamp irradiation.

Synthesis of a series of novel fused pyrazolines and pyrazoles has been accomplished in good yields by regio- and diastereoselective 1,3-dipolar cycloaddition of enamines of indan-1-one 1a-c towards C-aryl-N-phenylnitrilimines 2df. The structure of the cycloadducts was elucidated by 1D and 2D NMR studies.

Beckmann rearrangement of a variety of ketoximes has been carried out in imidazolium-based ionic liquids in the presence of catalytic amount of stannous chloride. This mild and ‘green’ procedure is highly regioselective affording the corresponding N-substituted amides in good to quantitative yields.

An ultrasonic-assisted, one-pot, efficient, convenient procedure for the synthesis of (3-phenylisoxazol-5- yl)methanol derivatives has been developed. (3-Phenylisoxazol-5-yl)-methanol derivatives with biological and pharmaceutical property have been synthesized in moderate to excellent yields. The synthetic methods possess the advantages of high yield, facile operation process and shorter reaction time, and so on.

An efficient and convenient approach towards the synthesis of series of tetrahydro-4H-chromenes via one pot three component coupling reactions of aldehyde, dimedone and malononitrile carried out at room temperature in presence of triethylammonium acetate [TEAA] ionic liquid as a catalyst. Reusability of the catalyst with optimized reaction conditions has also been investigated. The present methodology was found to be economically feasible and environmentally benign.

A convenient and efficient synthesis of symmetrical functionalized biaryls from aryl halides catalyzed by 10% Pd/C (2.0mol%) in the presence of Na3PO4.12H2O and MeOH has been developed. Aryl bromides bearing electron withdrawing and electron donating groups provided homocoupling products in excellent yields. Aryl chlorides and aryl iodides provided homocoupling products in good yields. The substrates with easily reducible functional groups were also effective.

Floricil (60-100nm, activated)-based Batch Molecular Reactors have been assembled and used in a variety of conventional synthetically useful free radical transformations (Hydrogen Transfer Reactions, Radical Cascade Reactions and Addition to C=C and C=N bonds). Reactions proceeded smoothly in all cases in good to excellent yields at ambient temperature in aqueous and organic media. The advantages of newly assembled setup are ease of setup, recyclability of the solid media, flexibility and scope of the transformations to be performed and ease of scale-up of methodology.