Letters in Organic Chemistry - Volume 6, Issue 6, 2009

The double addition of organolithium compounds and allylzinc bromide to the imines prepared from (R,R)-1,2- diaminocyclohexane by condensation with aromatic and heteroaromatic aldehydes gave secondary diamines with high yields and diastereoselectivities apart for the reaction of 2-pyridinealdehyde derivative which occurred with low to moderate stereocontrol.

A novel, mild synthesis of aryl-3,3,3-trifluoropropenes by Wittig olefination of benzylphosphonium ylides with in-situ generated trifluoroacetaldehyde is described. The in-situ formed trifluoroacetaldehyde efficiently traps the Wittig ylides and yields trifluoromethyl alkenes without the troublesome handling. The scope of the reaction was tested in reaction of trifluoroacetaldehyde with a wide variety of benzylphosphonium ylides. The α-trifluoromethyl alkenes were isolated in good to excellent yields in a convenient one step process.

The selective synthesis of unsaturated N-acylethanolamines 1b-6b by lipase-catalyzed direct condensation between unsaturated fatty acids 1a-6a and ethanolamine is reported. Reactions were carried out in hexane at 40 °C, in the presence of Candida antarctica Lipase B as the catalyst, to give the corresponding amides 1b-6b with yields ranging from 80 to 88%.

Ionic liquids as solvents were used effectively in palladium catalysed aminocarbonylation of 17-iodo-5α- androst-16-ene (1) with L-amino acid esters. Interestingly, optimal conditions that are essential for the successful reuse of the ionic liquid/catalyst mixture differ greatly from those observed in the similar reaction with simple secondary amines as nucleophiles.

A novel approach towards the synthesis of hitherto unreported oxathiocine derivatives has been described by utilizing palladium-catalyzed intramolecular Heck reaction starting from deactivated allylic compounds.

Starch sulfonic acid was used as efficient and highly stereoselective catalyst for the three-component Mannich reaction of aldehydes, amines, and ketones in water at ambient temperature to afford the corresponding β-amino ketones in good to excellent stereoselectivity and yields.

The S-alkylated indolyloxadiazoles 2a-l were obtained regioselectively by alkylation of 5-(1H-indol-2-yl)- 1,3,4-oxadiazole-2(3H)-thione 1, using TEA as acid scavenger. Alkylation of 1 with 1-bromopropane, 1-bromobutane, 1- bromoundecan, in the presence of K2CO3, yielded the N-alkylated products 3i-j,m in addition to the S-alkylated analogs 2i-j,m. A facile thio-aza-Claisen rearrangement (S??N allylic rearrangement) of the S-allyl-oxadiazole 2k to the N-allyl analog 3k was achieved in excellent yield. Further allylation of 2k and 3k in the presence of K2CO3 led to allylation of the NH indole ring producing 5 and 6, respectively. Benzylation of 1 in the presence of K2CO3 yielded 7 which resisted the S→N migration of the benzyl group. The 1H NMR, 13C NMR and mass spectra confirmed the structures and differentiated between the N- and S-alkylated products.

A simple and efficient method has been developed for the synthesis of α-aminophosphonates by a one-pot three-component condensation of aldehydes, amines and diethyl phosphite in the presence of a catalytic amount of silica sulfuric acid under solvent-free reaction conditions. The major advantages of the present method are good yields, inexpensive, ecofriendly and reusable catalyst, short reaction times, mild and solvent-free reaction conditions.

The efficient synthesis of dithieno[3,4-b:3',4'-d]thiophene was improved by the introduction of TMS groups in four synthetic steps including TMS protection, sulfidation, intramolecular cyclization, and TMS removal. The total yield is 55-63% with 3,4-dibromothiophene as starting material. In addition, the crystal structure of (TMS)4-dithieno[3,4-b:3',4'- d]thiophene was described.

A novel synthesis of 1,4- and 1,5-dioxepan-2-one lactones was achieved through the regioselective oxidation of 3-(2-hydroxyethoxy)propan-1-ol. Under basic conditions, when 3-(2-hydroxyethoxy)propan-1-ol was oxidized using oxoammonium salts, a quantitative oxidative esterification was observed, resulting in a regioselective lactone ring closure. This oxidation was tailored to afford 1,4-dioxepan-2-one in very good yield.

A clean and efficient method for the synthesis of chalcones using phosphonium ionic liquid catalyst [PhosILCl] has been described. The method provides several advantages, such as mild reaction conditions, simple work-up procedure, afford high yields and ecofriendly. In addition, the green solvent ionic liquid was recovered and reused several times in subsequent reactions.

New hybrid monomers and polymers consisting of rigid π-conjugated rods flanked with trialkoxylsilane side chains have been successfully synthesized. It has been shown that the monomer undergoes a sol-gel process to form transparent gels, from which the organic rods can be subsequently removed to produce nanoporous materials.

A library of 4-(3-acyl- or carbamoylaminoimidazo[1,2-a]pyridin-2-yl)benzamides (8) was synthesized on solid phase. A suitably protected core acid (1) was synthesized in multigram quantity using previously published procedure and used as the acylating reagent for modifying a set of AMEBA resins. Subsequent liberation of the amino group (using a novel hydrazine procedure) and its acylation or carbamoylation provided, after cleavage, final products in higher chemical yields and purities compared to known protocols that include formation of the imidazo[1,2-a]pyridine core on solid support.

Crystalline ammonium (9H-fluoren-9-yl)methyl H-phosphonate was prepared by a new, simple method and it was used as the reagent of choice for the introduction of an H-phosphonate monoester functionality into non-lipophilic anti-HIV nucleoside analogues.

Acetylcholinesterase inhibitors are currently of high interest due to the many reasons. Among them, Alzheimer's disease drugs are of great interest. In this study, eleven monoquaternary pyridinium salts substituted by different groups (electron donors and electron acceptors) in position four were prepared. Then, their anticholinesterase activity was tested. As observed, their IC50s ranged from 33 μM to 3981 μM. Moreover, probability of blood-brain barrier penetration was predicted.

The deprotection of O-protected (Z)-α-methyl-γ-hydroxy-α,β-unsaturated ester 1 furnishes dimer 2 when the reaction is performed under a nitrogen atmosphere, while compound 3 forms when the reaction is performed under an oxygen atmosphere.

The tandem isomerization-Mannich reaction of octen-3-ol and benzylidene N-sulfonyl imine affords the corresponding β-aminoketones in good yields. Diastereoselective reduction, followed by the deprotection of the primary amine, gives the expected 1-amino-2-methyl-1-phenyloctan-3-ol derivatives in excellent yields and in diastereomerically pure forms.

A convenient one-pot synthesis of 1-alkyl-7-chloro-6-flouro-3-nitro-1,4-dihydro-4-quinolones is described via nitro-decarboxylation of the respective 4-oxo-1,4-dihydroquinoline-3-carboxylic acid precursors. Reduction of the former 3-nitroquinolones delivered the corresponding 3-aminoquinolones, envisaged as valuable synthons in drug research.