Glycosidation via conjugate addition of anomeric alkoxides to nitroalkenes and nitrosoalkenes

The conjugate addition reactions of protected pyranose alkoxides to both nitroalkenes and nitrosoalkenes, as a route to 2-nitroalkyl, 2-oximinoalkyl and 2-oxoalkyl glycosides, are described.     

Catalytic asymmetric addition of beta-keto phosphonates to an activated imine--formation of optically active functionalized phosphonate alpha-amino acid derivatives

The direct stereoselective addition of an activated imine to beta-keto phosphonates in the presence of chiral Lewis acid complexes is developed. The evaluation of different activated imines shows that an N-tosyl-alpha-imino ester adds in a diastereo- and enantioselective fashion to beta-keto phosphonates activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases and other additives, shows that high yields, moderate diastereoselectivity and good enantioselectivity are obtained. The scope of the reaction is demonstrated for the reaction of beta-keto phosphonates and finally, the mechanism for the catalytic stereoselective step is presented.     

Asymmetric synthesis of beta-nitro ketones via Michael addition of lithiated alpha-amino nitriles to nitroalkenes

Alpha-amino nitriles, easily prepared from aldehydes, KCN, and an enantiopure secondary amine auxiliary, are metalated and used as nucleophiles in asymmetric Michael additions to nitroalkenes to afford the Michael adducts in good yields and good to excellent diastereoselectivities. After chromatographic purification, the diastereomerically pure 1,4-adducts are cleaved under acidic conditions to give the beta-nitro ketones in good yields and with two exceptions in good to excellent enantiomeric excesses (ee = 86-99%). The absolute configuration was determined by X-ray structure analysis.     

Direct asymmetric Michael addition of phthalide derivatives to chalcones

The Michael addition of phthalides to chalcones employing a quinidine-derived thiourea catalyst Q-1 has been developed. The reported method led to the synthesis of 3,3-disubstituted phthalide derivatives in excellent yields, with excellent diastereo- and enantioselectivities.     

Copper-catalyzed asymmetric conjugate addition of diethylzinc to substituted chalcones using a chiral phosphine ligand

A series of chiral phosphine PFAM and phosphine oxide POFAM ligands were studied for the copper-catalyzed asymmetric diethylzinc addition to enones. One of these ligands, PFAM2, was an efficient catalyst with a variety of enones to give conjugate addition products in up to 96% yield and 92% ee.     

Enantioselective conjugate addition of silylketene acetals to beta-enamidomalonates. Synthesis of beta-amino acid derivatives

[reaction: see text] Conjugate addition of silylketene acetals or enolsilanes to enamidomalonates proceeds with excellent chemical efficiency and good selectivity using Cu(OTf)2 and a chiral bisoxazoline. The effect of the Lewis acid, ligand, the N-acyl substituent, and the nucleophile on yield and selectivity for the addition product have been evaluated.     

Studies on pyrimidine derivatives. Michael addition of β-nitrostyrenes to substituted 6-aminouracils

A series of 5-(2-nitro-l-phenyl)ethyluracils were obtained when β-nitrostyrenes were reacted with 1,3-di-methyl-6-substituted uracil derivatives, instead of cyclic compounds. The structures of the compounds 5, 6 , and 7 were proved by spectroscopic methods and their mass fragmentation patterns are discussed.     

Iron chloride enhancement of dimethylzinc-mediated radical conjugate addition of ethers and an amine to alkylidenemalonates

The addition of FeCl₃ and the use of DMSO as a solvent enabled the radical conjugate addition of a cyclic acetal and a cyclic amine to alkylidenemalonates using a reagent amount (12.5 equiv) of the radical precursors to give Michael addition products in up to 84% yield. This represents a great improvement over the 5% yield obtained under the previously reported conditions.     

Simple chiral sulfonamide primary amine catalysed highly enantioselective Michael addition of malonates to enones

A chiral sulfonamide primary amine-organocatalysed, highly enantioselective Michael addition of malonates to enones has been developed. This reaction afforded the corresponding products in excellent yields (up to 99%) and excellent enantioselectivity (up to 99% ee).     

Asymmetric Michael addition of N-boc-protected oxindoles to nitroalkenes catalyzed by a chiral secondary amine

New mission for prolinol ethers: A secondary-amine-catalyzed Michael addition of N-Boc-protected oxindoles to nitroalkenes through a Br?nsted base activation mode has been developed, furnishing the products in excellent yields (88-98?%), diastereoselectivities (d.r.=98:2->99:1) and high to excellent enantioselectivities (82->99?%?ee; see scheme).     

Highly enantioselective Michael addition of aldehydes to nitroolefins catalyzed by primary amine thiourea organocatalysts

Asymmetric Michael addition reactions of aldehydes to nitroolefins have been successfully initiated by a series of primary amine thiourea bifunctional catalysts, with high enantioselectivities (90-98% ee) and excellent yields (80-96%). The privileged quinine scaffold was found to be essential to the reaction efficiency and enantioselectivity.     

Highly diastereoselective addition of nitromethane anion to chiral alpha-amidoalkylphenyl sulfones. Synthesis of optically active alpha-amino acid derivatives

Optically active syn-alpha-amidoalkylphenyl sulfones can be prepared from chiral aldehydes in anhydrous conditions using benzenesulfinic acid. These sulfones in basic conditions give N-acylimines that react with sodium methanenitronate to afford the corresponding nitro adducts with high anti diastereoselectivity. PM3 semiempirical calculations provide a rationale for the observed opposite stereoselectivity. The obtained nitro derivatives undergo a Nef reaction followed by a methylation giving optically active beta-hydroxy-alpha-amino acid and alpha,beta-diamino acid esters in good yield. These amino acid derivatives are important building blocks for the preparation of biologically active compounds.     

Diastereoselective intermolecular addition of the 1,3-dioxolanyl radical to N-acyl aldohydrazones. Asymmetric synthesis of alpha-amino acid derivatives

[reaction: see text] N-Acyl aldohydrazones I (R = CO(2)Et, alkyl, aryl, and furyl) efficiently trap the 1,3-dioxolanyl radical intermolecularly without external activation at temperatures as low as -78 degrees C. For alkyl aldohydrazones, good diastereoselectivities are obtained in the presence of InCl(3) at low temperature. Elaboration of the adducts (II) allows for the asymmetric synthesis of alpha-amino acid derivatives.     

The diastereospecific aprotic conjugate addition reactions of carbanions derived from allylic sulfoxides and allylic phosphine oxides.

The title carbanions undergo conjugate addition to cyclic enones in THF to deliver vinylic sulfoxides and vinylic phosphine oxides as single diastereomers.     

Kinetics and mechanism of nucleophilic addition to nitric oxide: secondary amine diazeniumdiolation

The kinetics of nitric oxide (NO) addition to dipropylamine and pyrrolidine are determined for a range of solvents and NO pressures. A new isobaric technique is utilized to determine the order of NO, and the kinetics are shown to conform to reactions which are either mono- or bimolecular in NO depending upon the conditions. The mechanism is interpreted in terms of competitive addition of amine to either NO or its dimer.     

Novel codeinone derivatives via Michael addition of barbituric acids

Two novel adducts of codeinone with barbituric and 2-thiobarbituric acids have been synthesized via Michael addition. The compounds were spectroscopically elucidated by means of IR-LD spectroscopy of oriented samples as a suspension in nematic liquid crystals, UV spectroscopy and ¹H and ¹³C NMR spectroscopy. The 2-thiobarbituric adduct was characterized by X-ray crystallography. HPLC tandem mass spectrometry (HPLC ESI MS/MS) and thermal methods were also employed. Quantum chemical calculations have been performed with a view to obtaining the electronic structure and vibrational properties of the novel compounds.     

Alternatives to 1-H-tetrazole in the preparation of phosphonate diesters and phosphonamidates from phosphonyl dichlorides

5-Ethylthio-1-H-tetrazole (SET) and 4,5-dicyanoimidazole (DCI) were examined as alternatives to 1-H-tetrazole to mediate the synthesis of phosphonate diesters and phosphonamidates from phosphonyl dichlorides through a two-step one-pot reaction in various organic solvents. SET and DCI were comparable to 1-H-tetrazole for catalyzing these reactions. SET afforded slightly greater yields than DCI while benzene was universally the best solvent for this reaction.