Letters in Organic Chemistry - Volume 5, Issue 2, 2008

Symmetrical and unsymmetrical spiro-bis-imides and corresponding 3-methoxycarbonyl succinimides were prepared in very good yields starting from dimethyl malonate and suitable α-bromoacetamides in a one-pot procedure or two-steps sequence, respectively. The mechanistic aspects of these transformations were also discussed.

A new, readily available double-component catalytic system for asymmetric Henry reaction has been discovered. The aromatic aldehydes reacted with nitromethane in THF under catalysis of threo-(1S, 2S)-TDMANPCu( OAc)2.H2O system to furnish β-nitro alcohols in good yields and up to 79% ee. This methodology is air-tolerant and easily operative, and the chiral amino alcohol can be conveniently synthesized from inexpensive chiral starting material.

A novel method for the construction of spirooxindole via imino Diels-Alder reaction of in situ generated isatin imine with dihydropyran is reported. InCl3 efficiently catalyzes the reaction to afford cis- and trans-diastereisomers in fairly good yields.

Reaction of 1,1,1-trichloro-4-methoxy-3-penten-2-one (1) with hydrazines (2a-h) (NH2NHR, R = H, Me, t-Bu, Ph, 4-NO2-C6H4, C6F5, CO2Me, CONH2) under differing conditions regiospecifically affords different pyrazole derivatives, 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydropyrazoles (3a, d-h), 3-methyl-5-trichloromethyl-1H-pyrazoles (4a,b,d-g) and 5-carboxyethyl-3-methyl-1H-pyrazoles (5a-e). The structural assignments were based on the analysis of their 1H/13C NMR and ESI-MS data.

Due to the profound cytotoxicities and interesting biochemical aspects, phenanthroindolizidine alkaloids have received attention as potential therapeutic leads. To define the features of the molecule that are essential for their excellent bioactivities, we have synthesized two hexahydropyrrolo[1,2-b]isoquinolines and their hydrochloride salts and picrates concisely and evaluated their antiviral and anticancer activities. We found that the replacement of the phenanthrene with a benzene in phenanthroindolizidine alkaloids observably decreased their antiviral and anticancer activities, and thus the phenanthrene in phenanthroindolizidine alkaloids is essential for high antiviral and anticancer activities.

The novel synthesis of aryl thiazolines (ATZ) is described and structures established by COSY, HSQC, HMBC and NOESY experiments. Compounds DCL-ATZ and Me-ATZ displayed cytotoxic activities against a neuroblastoma, a platinum-resistant ovarian adenocarcinoma and a prostate adenocarcinoma cell line. Me-ATZ displayed differential antiproliferative effects.

Ring closing metathesis protocol on bis-allylic chirons derived from sugars was utilized for the stereoselective synthesis of spiro C-linked deoxy disaccharides. Uloses derived from D-xylose and L-sorbose were converted into bisallylic derivatives, which on RCM gave the spiro-pyrane rings. The xylose-derived spiro-pyrane on sequential oxidations was converted into new deoxy spiro C-disaccharides.

A variety of amines were protected as their N-Boc derivatives using phosphomolybdic acid supported on silica gel as a heterogeneous catalyst. The catalyst is more effective and highly selective for the protection of amines under mild conditions and it can be recovered and reused in subsequent reactions without apparent loss of activity.

The coupling of 5-membered heterocyclic amines such as pyrazole and imidazole derivatives with heteroaromatic chlorides like 4,7-dichloroquinoline, 2-chlorobenzoxazole and 2-chlorobenzothiazole has been realized in good yields using very simple solvent-free conditions.

In situ synthesis of benzyl chloromethyl ether and its use to protect bifunctional hydroxyl compounds as benzyloxymethyl ethers is reported. This methodology was extended to alkylate the N-protected L-amino acids.

Reaction of 3-mercapto-2-butanone with electron-deficient acetylenic esters in the presence of tert-butyl isocyanide leads to dialkyl 4-hydroxy-4,5-dimethyl-4,5-dihydro-2,3-thiophenedicarboxylates. These alcohols are converted to 2,3-dialkyl-4,5-dimethyl-2,3-tiophenedicarboxylates in boiling dichloromethane in fairly good yields. (E/Z) SFunctionalized vinyl sulfides are produced in this reaction as by- products.

A new pyrano[3,2-c] quinolinedione derivative was synthesized in three steps starting from Nmethylanthranilic acid. The synthesis was accomplished using both conventional thermal methods and microwave assisted procedures. The syntheses are more convenient when the microwaves are employed because of shorter reaction times, the elimination of waste solvents, and improved chemical yields.

A rapid and highly efficient protocol involving solvent free oxidation of organic halides using aqueous hydrogen peroxide under controlled microwave irradiation is described for the synthesis of carbonyl compounds.

A highly efficient one-pot, two-step sequential process consisting of modified Jones oxidation of aqueous cyclovirobuxine D acetate followed by Ruschig degradation after pH regulation with saturated aqueous NaOH, provided cyclobuxophyllinine M in high yield and in a single geometrical isomeric form.

A general and practical Green Chemistry route to the Biginelli cyclocondensation multicomponent reaction had been carried out by the three-component coupling of β-ketoesters, various structurally diverse aldehydes including heterocyclic aldehydes and urea/thiourea in the presence of Zirconia (ZrO2) nanopowder catalyst in dry media under microwave irradiation and a comparative study was also done under thermal conditions giving 3,4-dihydropyrimidin-2(1H)-ones and -thiones (DHPMs) in excellent yields. Besides, it was highlighted that ZrO2 nanopowder can be reused up to six times after simple washing with ethyl acetate, thus exposing the process economical and environmentally benign.

An efficient reductive amination of aldehydes and ketones in the preparation of aliphatic and aromatic secondary and tertiary amines with xylylene ionene borohydride as a high capacity polymer supported reducing agent in isopropanol at reflux under neutral conditions is described. Xylylene ionene borohydride is easily prepared by mixing an aqueous solution of xylylene ionene chloride with an alkaline solution of sodium borohydride at room temperature. The chemoselective reductive amination in the presence of functional groups such as chloride, C=C bond, nitro and cyano groups was also achieved. The generality of reaction was established using variety of aldehydes, ketones and amines.

Perchloric acid adsorbed onto silica gel (HClO4-SiO2) was found to be a highly efficient, inexpensive and recyclable catalyst for the selective α-bromination of carbonyl compounds using N-bromosuccinimide by stirring in n-hexane at room temperature under mild and heterogeneous conditions.