CuI/N,N-dimethylglycine-catalyzed synthesis of N-aryloxazolidinones from aryl bromides

CuI/N,N-dimethylglycine catalyzed coupling of aryl bromides with substituted oxazolidinones took place at 120 °C in DMF, affording the corresponding N-arylation products with good to excellent yields. A number of functional groups, such as ketone, nitrile, nitro, methoxy, and hydroxyl were tolerated under these conditions, thereby allowing diversity synthesis of N-aryloxazolidinones.     

SmI2-promoted intra- and intermolecular C-C bond formation with chiral N-acyl oxazolidinones

The suitability of chiral oxazolidinones in the SmI₂-mediated C-C bond generation between the imide functionality of an N-acyl oxazolidinone unit and an olefinic radical acceptor, in both inter- and intramolecular reactions, was investigated. It was shown that the products from an Evans asymmetric alkylation can undergo direct carbon-carbon bond formation with an acrylamide providing chiral acyclic ketones in reasonable yields. These examples represent the first transformation of such N-acyl oxazolidinones where this chiral auxiliary is removed under the conditions for ketone formation. 5-exo-trig Cyclization studies were also undertaken with the same type of substrates, providing trans-2,5-disubstituted cyclopentanones in yields of approx. 50%. However, attempts to cyclize heteroatom-containing equivalents were less rewarding.     

Facile synthesis of dihaloheterocycles via electrophilic iodocyclization

An efficient and facile electrophilic iodocyclization for the synthesis of various O-, N-, and S-containing dihaloheterocycles has been developed. A wide range of the substituted propargyl alcohols having -OH, -NTs, and -SAc functional groups reacted with molecular iodine or bromoiodine at ambient temperature to produce the corresponding dihalogenated O-, N-, and S-containing five- and six-membered heterocycles in good to high yields; Under optimized solvent conditions, the reactions of various substituted but-2-yn-1-ones bearing -OH, -NTs, and -SAc functional groups at C4-position, with iodine or bromoiodine at ambient temperature afforded the corresponding 3,4-diiodo- and 3-bromo-4-iodo-substituted furans, pyrroles, and thiophenes in good to high yields. Further transformation of the resulting iodine- or bromine-containing products to polyaromatics potentially of useful as organo-material intermediates has been investigated.     

Synthesis of novel 3-bromo-1,2-dihydroquinolines via palladium mediated intramolecular cyclization of N-tosyl-N-propargyl anilines

Facile synthesis of novel 3-bromo-1,2-dihydroquinolines by the intramolecular cyclization of N-tosyl-N-propargyl anilines catalyzed by Pd(OAc)₂ in conjunction with CuBr₂ and LiBr.     

Stereoselective synthesis of N,N-acetals by cyclization of an N-acyliminium ion through interaction with an N-sulfonyl group

A new method for the stereoselective synthesis of five- and six-membered bicyclic N,N-acetals with trans configuration was developed using N-acyliminium ion cyclization. The N-sulfonyl substituted compounds were effectively cyclized to give the corresponding acetals in high yields and stereoselectivities, suggesting that the intramolecular interaction between the iminium and the sulfonyl group plays a key role in the cyclization.     

Architecturally diverse heterocycle formation by N-acyliminium ion initiated cyclization

Enaminoesters containing a tethered indole or aryl moiety on the amine react with substituted maleic anhydrides or acryloyl chlorides to provide pyrrolinone or dihydropyridone products, respectively. The indole-tethered dihydropyridones can be induced to undergo a one-pot cyclization whereas, the indole-tethered pyrrolinone intermediates are readily cyclized with HCl. The aryl-tethered pyrrolinones or dihydropyridones can be isolated and subsequently induced to cyclize with triflic acid. This methodology culminates in the synthesis of erythrane-like and other natural products that are readily amenable to combinatorial library production.     

Alkylation of sterically hindered 1,3-diketones under phase-transfer conditions

Sterically hindered 1,3-diketones react selectively with propargyl and allyl bromides under conditions of phase transfer catalysis to giveC-alkylated products, whereas reactions with butyl and benzyl chlorides yield mixtures ofC- andO-isomers. An increase in the size of the substituents present in the initial 1,3-diketone hampers introduction of the second propargyl group. The propargyl-substituted 1,3-diketones undergo cyclization under the alkylation conditions to give substituted furans.     

Single-step conversion of N-benzyl, N-trityl and N-diphenylmethyl amines to t-butyl carbamates using polymethylhydrosiloxane

t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenylmethyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under Pd(OH)₂/C catalysis.     

New approach to preparation of N-acylphosphoramido(thio)(seleno)ates

N-[2-(X)-1,3,2-Oxathiaphospholane] derivatives (X = S, Se, O) of carboxamides were prepared and their DBU-assisted reaction with alcohols led to the corresponding O-alkyl-N-acylphosphoramido(thio)(seleno)ates. Their structures were confirmed by MS analysis and ¹H and ³¹P NMR spectroscopy. Independently N-acylphosphoramidoselenoates were converted to N-acylphosphoramidates by treatment with tert-butylperoxytrimethylsilane. The oxathiaphospholane approach was also applied to the synthesis of derivatives having N-prolylphosphoramido(thio)(seleno)ate linkages on the 5′-OH group of AMP.     

N-Aryl-2-nitrosoanilines as intermediates in the synthesis of substituted phenazines from nitroarenes

N-Aryl-2-nitrosoanilines, available from the reaction of nitroarenes with anilide anions, undergo cyclization to furnish substituted phenazines. The reaction is promoted by potassium carbonate in methanol, N,O-bis(trimethylsilyl)acetamide (BSA) in aprotic solvents, and by acetic acid. The method is illustrated by the synthesis of 1-methoxyphenazine, a precursor of pyocyanine, starting from the appropriate nitroarene-aniline pairs.     

Effective protection of the N-sulfate of glucosamine derivatives with the 2,2,2-trichloroethyl group

The 2,2,2-trichloroethyl (TCE) group was utilized as the first protecting group for N-sulfates (chlorosulfuric acid TCE ester, Et₃N, DMAP, DMF). Glycosylation with 3,4,6-tri-O-acetyl-N-trichloroethylsulfuryl-α-d-glucosaminosyl trichloroacetimidate provided the corresponding β-glucosaminosides stereoselectively and in excellent yields. The TCE protection stayed stable under a variety of conditions for the manipulation of other protecting groups, and was readily removable with zinc in the presence of ammonium chloride in methanol.     

Synthesis of N-benzothiazol-2-yl-amides by a copper-catalyzed intramolecular cyclization process

Employing N-(4,5-dihydrooxazol-2-yl)benzamide as novel and efficient ligand, the copper-catalyzed intramolecular cyclization of various substituted 1-acyl-3-(2-bromophenyl)thioureas could be successfully carried out under mild conditions. A variety of N-benzothiazol-2-yl-amides were synthesized in good to excellent yields.     

Synthesis of N-methyl-d-ribopyranuronamide nucleosides

The synthesis of N-methyl-d-ribopyranuronamide nucleosides is described. The key route is the rearrangement of a 1,2-O-isopropylidene protected furanose sugar with a carboxamide function in the 4-position to a ribopyranuronamide ring. The Lewis acid catalyzed condensation of adenine and thymine nucleobases with the per-O-acetylated N-methyl-d-ribopyranuronamide sugar is used to give the target nucleosides as a mixture of the α and β anomers. The mixture was separated and the final compounds were obtained by deacetylation in basic conditions.     

A new route to (±)-erythro-roccellic acid and chaetomellic anhydride C through functional rearrangement, promoted by n-propylamine or CH3ONa/CH3OH, of N-propyl-3-chloro-4-dichloromethyl-3-dodecylpyrrolidin-2-one

The rearrangement of a trichloro-pyrrolidin-2-one, prepared by the CuCl-TMEDA catalyzed atom transfer radical cyclization of N-alkyl-N-(3-chloro-2-propenyl)-2,2-dichloromyristamide, with n-propylamine or CH₃ONa/CH₃OH, is the key step of a new, short and inexpensive route to chaetomellic anhydride C and (±)-erythro-roccellic acid.     

X-ray crystallographic analysis of N,N-diallylcoumarincarboxamides and the solid-state photochemical reaction

X-ray crystallographic analysis and the photochemical aspects of N,N-diallylcoumarincarboxamides were investigated. Irradiation of the corresponding amides promoted stereoselective intramolecular cyclobutane formation exclusively. The solid-state photoreaction of the coumarinamide without substituent on the 4-position proceeded in a crystal-to-crystal manner. On the other hand, photolysis of the amide possessing a methyl group at the 4-position also effected 2+2 cycloaddition; however, the reaction proceeded much slower. The difference in the reactivity was explainable on the basis of the molecular conformation in the crystal lattice.     

Microwave-assisted deformylation of N-aryl formamide by KF on basic Al2O3

The formyl group was successfully removed from N-aryl formamide by KF on a solid support of basic Al₂O₃ in 4-20 min with microwave irradiation. The conditions mimic base-catalyzed hydrolysis of formamide and are compatible with carbamates and t-butyl esters, but not methyl, ethyl, and benzyl esters.     

Preparation of N-alkyl-N′-carboalkoxy guanidines: unexpected effective trans-alkoxylation transforming the 2,2,2-trichloroethoxycarbonyl into various carbamates

A range of N-alkyl-N′-Boc guanidines was simply synthezized from monoprotected Boc-1H-pyrazole-1-carboxamidine by reaction with primary amines. Synthesis of the hindered (R)-N-methylbenzyl-N′-Troc guanidine was achieved from the corresponding thiourea by the action of ammonia. Transformation of the Troc group into others carbamate groups, including Boc, was simply obtained by refluxing in the appropriate alcohol.     

An effective synthesis of N,N-dimethylamides from carboxylic acids and a new route from N,N-dimethylamides to 1,2-diaryl-1,2-diketones

Carboxylic acids were heated at 150 °C in DMF in the presence of 1.25 equiv of thionyl chloride to give corresponding N,N-dimethylamides in good yields. Tandem chlorination and amidation reactions occurred in the one-pot procedure. Dicarboxylic acids needed prolonged reaction time to produce bisamides in good yields. Some benzamides were efficiently converted into corresponding 1,2-diaryl-1,2-diketones (benzils) under acyloin condensation conditions in the presence of 4,4′-di-tert-butylbiphenyl (DBB) in THF. Ultrasonic irradiation effectively accelerates the reaction, but it is not critical. However, the presence of DBB is fatal to the reaction. Although a few synthetic methods for benzils from benzoic acids have been reported so far, this method is one of the most convenient and highly reproducible procedures.     

Stereospecific N-oxide-mediated monoprotection of trans-3,4-dihydroxypyrrolidine derivatives

We found that the syntheses of O-monosubstituted 1-N-alkyl-trans-3,4-dihydroxypyrrolidines, normally faces serious obstacles due to poorly reactive hydroxy groups as a consequence of the presence of a highly basic pyrrolidine nitrogen atom, but that they can be obtained easily in high yields by conversion of 1-N-alkyl-trans-3,4-dihydroxypyrrolidines into the corresponding N-oxides. N-Oxidation leads to the loss of the pyrrolidine nitrogen atom basicity and discrimination in the reactivity of the originally equivalent hydroxy groups by at least one order of magnitude. The reaction of N-oxide derivatives with DMTrCl or TBDPSCl then proceeds in an almost quantitative yield, rapidly, and stereospecifically on the hydroxy group which is in a cis-position to the N-oxide oxygen atom. In contrast to the TBDPS derivative, the DMTr derivative could be easily deoxygenated with triphenylphosphine in high yield. The structures of the products obtained were confirmed by 2D NMR experiments, and quantum-chemical calculations were performed to explain the reaction mechanism of the stereospecific course of the reaction.     

σ-P Ligands: convenient syntheses of N-methyl-1,3-benzazaphospholes

A convenient three-step route to 1,5-dimethyl-1,3-benzazaphosphole via Cu- or Pd-catalyzed phosphonylation of 2-iodo-4-methylaniline, reduction to 2-phosphino-4-methylaniline, and disproportionative cyclization with excess formaldehyde is reported. N-Methylbenzazaphospholes can be functionalized in the 2-position via α-CH-lithiation with tBuLi and are π-acidic σ²P-ligands.