Synthesis of cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans

Substituted cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans are synthesized in modest overall yields starting from 4-aryl-1,2,5,6-tetrahydropyridines and 4-aryl-1,2,5,6-tetrahydropyrans via the following sequence: (1) pinacol-type ring contraction having the combination of m-chloroperoxybenzoic acid and boron trifluoride etherate, (2) Grignard addition with arylmagnesium bromide reagents and followed by boron trifluoride etherate-mediated intramolecular ring-expanded rearrangement, and (3) hydrogenation with hydrogen on 10% palladium-activated carbon. A facile synthesis of 3,4-diarylpyridines was also described by base-induced aromatization.     

DBU-assisted 1,3,2-oxathiaphospholane ring-opening condensation with selected O-, S-, N- and C-nucleophiles

The reactivity of protected thymidine 3′-O- and 5′-O-(2-thio-1,3,2-oxathiaphospholanes) towards various nucleophiles in the presence of DBU is presented and mechanistic implications are discussed.     

Synthesis of 5-endo-, 5-exo-, 6-endo- and 6-exo-hydroxylated analogues of epibatidine

A convenient, high-yield synthesis of N-Boc-7-azabicyclo[2.2.1]hept-5-en-2-one (7) was developed by SmI₂-mediated desulfonylation of 6. Thus, 5-endo-, 5-exo-, 6-endo-, and 6-exo-hydroxylated epibatidine analogues 2a,b and 3a,b were synthesized from 7 by using a Pd(PPh₃)₄-catalyzed reductive Heck coupling reaction and SmI₂-mediated reduction of the carbonyl group as the key steps. Other reaction conditions for the reductive Heck procedure and the reduction step were also investigated.     

pentahapto- UND trihapto- cycloheptadienylkobalt(I)-komplexe

Treatment of [CoH(N₂)(PPh₃)₃] with cycloheptatriene in diethyl ether affords [Co(1—5-η-C₇H₉)(PPh₃)₂] (I). An etherical solution of (I) reacts with CO at room temperature and under normal pressure to yield the carbonyl complex [Co(1—3-η-C₇H₉)(CO)₂(PPh₃)] (II). These compounds are characterized by their PMR and IR spectra.     

Theoretical conformation studies of anti- and syn-4-pyrimidinecarboxaldehyde oxime

A conformational analysis of the twist angle in anti- and syn-4-pyrimidinecarboxaldehyde oxime has been carried out using the EHT, INDO and PCILO methods. All three methods predict very low rotation barriers so that in solution a model assuming geometrical flexibility is probably applicable.     

Stereoselective multigram-scale synthesis of cis- and trans-β-phenylproline derivatives

Efficient routes for the gram-scale preparation of the proline analogues that bear a phenyl substituent attached to the pyrrolidine β carbon (cis- and trans-β-phenylproline) have been developed. The cis derivative was synthesized from N-Boc-β-alanine in six steps and 78% overall yield. The generation of a vinyl triflate with full regiochemical control together with a high-yielding cross-coupling reaction and a completely stereoselective hydrogenation are at the basis of the high efficiency of the procedure. Epimerization of the cis β-phenylproline derivative with lithium bis(trimethylsilyl)amide provided access to the trans isomer.     

ortho-, meta- and para-nitrophenylgold(I) complexes

Treatment of [BzPh₃P][AuCl₂] with [Hg(x-C₆H₄NO₂)₂] (x = o, m, or p) gives anionic gold(I) complexes of the type [BzPh₃P][Au(R)Cl](R = o-, m- or p-C₆H₄NO₂, Bz = C₆H₅CH₂). The chloro ligand in [Au(o-C₆H₄NO₂)Cl]^? can be replaced by bromo or iodo ligands by use of NaBr or NaI. The anions [Au(R)Cl]^? react with neutral monodentate ligands, L, to give neutral mononuclear complexes [Au(R)L] (R = o-C₆H₄NO₂, L = PPh₃, AsPh₃; R = m-C₆H₄NO₂, L = PPh₃) and with 1,2-bis(diphenylphosphino)ethane (dpe) to give [Au₂(R)₂(dpe)] (R = o-C₆H₄NO₂). The corresponding [Au(p-C₆H₄NO₂)Cl]^? reacts with PPh₃ or AsPh₃ to give mixtures containing [AuClL]. The anionic ortho-nitrophenylgold(I) complex is much more stable than its meta- or para-nitrophenyl isomers. These are thought to be the first reports of nitrophenylgold(I) complexes.     

New stereoselective syntheses of cis- and trans-2-methyl-4-arylpiperidines

A stereoselective approach has been developed for the synthesis of cis- and trans-2-methyl-4-arylpiperidines from a common intermediate. The Ni-catalyzed hydrogenolysis of N-Boc-2-methyl-4-aryl-4-piperidinols, obtained by addition of organometallic reagents on N-Boc-2-methyl-4-piperidone, afforded the trans derivatives with up to 95% selectivity whereas the corresponding cis isomers were obtained in the presence of palladium catalysts.     

Facile stereoselective synthesis of cis- and trans-3-alkoxyazetidin-2-ones

A highly stereoselective synthesis of cis- and trans-3-alkoxy-3-phenyl/benzylthioazetidin-2-ones is described. The reaction of α-chlorosulfide-β-lactams with various alcohols catalyzed by a Lewis acid such as ZnCl₂ in the presence of molecular sieves (3-4 Å) leads to cis-3-alkoxy-3-phenyl/benzylthio-β-lactams whereas treatment of potassium 2-alkoxy-2-phenylthioethanoate with appropriate Schiff's base using POCl₃ in the presence of triethylamine leads to the formation of trans-3-alkoxy-3-phenylthioazetidin-2-ones as major products.     

Palladium-catalyzed stereoselective synthesis of E- and Z-1,1-diaryl or triarylolefins

A stereoselective and flexible synthesis of various E- and Z-1,1-diaryl and triarylolefins 3 was achieved from readily available vinylstannanes 1 via stereospecific iodo-destannylation and subsequent palladium-catalyzed Negishi-type cross-coupling reaction with arylzinc reagents under mild conditions.     

Electrophilic monofluoromethylation of O-, S-, and N-nucleophiles with chlorofluoromethane

CH₂ClF has been found to be a useful electrophilic monofluoromethylating agent for a variety of O-, S-, and N-nucleophiles. The reaction is not sensitive to the radical scavenger such as nitrobenzene, which strongly supports an S_N2 mechanism rather than an SET mechanism. Although most of these products (fluoromethyl ethers, sulfides, and amines) can be isolated with good purity, some of these compounds do intend to decompose (via defluorination) during storage. The electrophilic monofluoromethylation of carbon-nucleophiles was attempted with CH₂ClF, CH₂FI, or FCH₂OTs as monofluoromethylating agents, but with no success.     

One-pot synthesis of meso-tris-aryl-substituted N-21-methyl- and N-21-benzyl-corroles

A simple and versatile synthesis of meso-substituted N-21-alkylcorroles was achieved directly from aldehydes, pyrrole and N-alkylpyrroles via mix-condensation. Compounds inaccessible via previous routes have been obtained in acceptable yields. It was proved that meso-substituted N-21-alkylcorroles differ from N-unsubstituted corroles in absorption spectra, stability and solubility.     

Synthesis of erythro- and threo-α-bromo-α′-fluorosuccinic acids

$\text{erythro}$- and $\text{threo}$-α-Bromo-α′-fluorosuccinic acids have been prepared from their corresponding dimethyl esters. Because of the extreme readiness of elimination of hydrogen fluoride in basic medium, a special method of acid hydrolysis had to be applied. Hydrogen and fluorine NMR spectra are reported.     

Syntheses of E- and Z-2- and 4-fluorourocanic acids

Horner-Wadsworth-Emmons olefination of ring-fluorinated N-trityl-imidazole carboxaldehydes with dialkyphosphonoacetic acid esters produced ring-fluorinated imidazolyl-E- and Z-acrylate esters. Stereochemistry was controlled by choice of phoshonate. Acid catalyzed removal of trityl followed by ester saponification gave the target 2- and 4-fluoro-E- and Z-urocanic acid derivatives. These are being investigated as potential mediators of photo-immunosupression.     

Stereoselective synthesis of cis- and trans-3-fluoro-1-phenylcyclobutyl amine

A stereoselective approach to the synthesis of cis- and trans-3-fluoro-1-phenylcyclobutylamine has been developed. Excellent stereoselectivity was obtained by the reduction of the appropriately substituted cyclobutanone to give either cis- or trans-isomers of 3-hydroxyl-1-phenylcyclobutylamine, which was stereoselectively converted to the 3-fluoro derivative.     

Baylis-Hillman chemistry: synthesis of cis- and trans-α-methylene-γ-lactones

syn-Homoallylic alcohols prepared from Baylis-Hillman adducts react with CBr₄/PPh₃ to give trans-α-methylene-γ-lactones. Notably, the same alcohols yield the cis-α-methylene-γ-lactones in the presence of traces of p-toluenesulfonic acid.     

Efficient preparation of 9-Z-11-methylretinal and 11-Z-11-methylretinal

[2-(β-Ionylidene)propyl]triphenylphosphonium bromide is reacted with 3-methyl-4-oxobut-2-enenitrile in refluxing 1,2-epoxybutane to give a mixture of 11-Z- and all-E-11-methylretinal via DIBAL-H reduction. In an analogous fashion, β-ionyl triphenylphosphonium bromide is reacted with 3,5-dimethyl-6-oxohexa-2,4-dienenitrile in 1,2-epoxybutane followed by subsequent DIBAL-H reduction to afford a mixture of new products consisting of 9-Z-11-methylretinal, its all-E isomer and 1-(2′,6′,6′-trimethylcyclohex-2′-en-1′-yl)-6-(buten-2″-al-3″-yl)-3,5-dimethylcyclohexa-1,3-diene. These molecules were obtained in pure form by HPLC.     

Synthesis of trans-vaccenic acid and cis-9-trans-11-conjugated linoleic acid

The preparation of the monounsaturated fatty acid, trans-vaccenic acid 4 (TVA), using both Wittig and one-pot Julia-Kocieński olefination protocol, was achieved in good yield. Similarly a Wittig approach was employed for the stereoselective synthesis of cis-9-trans-11-conjugated linoleic acid 2 from trans-2-nonenal and (8-carboxyoctyl)triphenylphosphonium bromide 12.     

Thermal and photochemical decomposition of cis- and trans-3,5-diphenyl-1-pyrazoline

The decomposition mechanism of the title compounds 8c and 8t is discussed. Dibenzylic 1,3-biradicals are suggested as intermediates.     

syn- and anti-(1-Alkyl-π-Allyl)palladium chlorides

π-Allylpalladium chlorides with bulky substituents on the terminal carbon atoms are often formed with these substituents in the less stable anti configuration. The activation energy of the π-σ-π rearrangement to the syn configuration increases with the bulkiness of the substituent. The difference in energy between the anti and syn configurations decreases with increasing size of the substituents on the terminal and meso carbon atoms. The phenomena can best be explained by assuming that there is steric interaction between the substituents on the terminal carbons of the π-allyl ligand and either other ligands on the metal or the substituent on the mso carbon of the π-allyl ligand.