Highly efficient one-pot, three-component Mannich reaction catalysed by boric acid and glycerol in water with major ‘syn’ diastereoselectivity

Boric acid and glycerol efficiently catalysed the one-pot, three-component Mannich reaction of aldehydes, aromatic amines and cyclic ketones in water at ambient temperature to afford the corresponding β-amino carbonyl compounds in good yields. All but one reaction proceeded with moderate ‘syn’ diastereoselectivity. This observation is just the reverse of the major anti diastereoselectivity obtained in most of the earlier reported procedures. The methodology is mild and efficient using minute quantities of catalyst with no side products and a very simple work-up procedure.     

Synthesis and NMR spectra of the syn and anti isomers of substituted cyclobutanes—evidence for steric and spatial hyperconjugative interactions

The syn and anti isomers of cis,cis-tricyclo[5.3.0.0^2,6]dec-3-ene derivatives have been synthesized and their ¹H and ¹³C NMR spectra unequivocally analyzed. Both their structures and their ¹H and ¹³C NMR chemical shifts were calculated by DFT, the latter two calculations employing the GIAO perturbation method. Additionally, calculated NMR shielding values were partitioned into Lewis and non-Lewis contributions from the bonds and lone pairs involved in the molecules by accompanying NBO and NCS analyses. The differences between the syn and anti isomers were evaluated with respect to steric and spatial hyperconjugation interactions.     

Synthesis and separation of the atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds

Several syn and anti atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds were synthesized from 1,1′-binaphthyl-2,2′-diol (BINOL). It was possible to separate the syn and anti atropisomers by silica gel column chromatography. The syn atropisomers are potential hetero-bidentate ligands for complex formation with metals. By starting from enantiomerically pure (R)-(+)-BINOL and (S)-(−)-BINOL, four optically active syn atropisomers and two anti atropisomers with high enantiomeric purity were obtained. The structures of two syn atropisomers and one anti atropisomer were established by X-ray structure analyses.     

Preparation of syn and anti cyclophanes having oligothiophene units and their spectral properties

Syn and anti cyclophanes consisting of oligothiophene units as a component have been synthesized for the first time. Correlation between the cyclophane structure and fluorescence spectral properties has been examined. Emission from intramolecular excimer-formation is confirmed for the syn cyclophanes and the mobile cyclophanes, but not for the anti cyclophanes.     

Highly enantioselective aldol reactions using a tropos dibenz[c,e]azepine organocatalyst

The four-step synthesis of a chiral primary tertiary diamine salt, possessing a tropos dibenz[c,e]azepine ring is described. It is shown that 3.5-5 mol % of this salt is capable of promoting highly enantioselective crossed-aldol reactions between cyclohexanone and a series of aromatic aldehydes. In all cases, the aldol reactions proceed with high diastereoselectivity for the anti-aldol product. The outcome of crossed-aldol reactions involving other cyclic ketones and acyclic ketones are also described. All examples involving cyclic ketones result in selectivity for the anti-aldol products, whereas acyclic ketones were found to favour the syn-aldol products. A discussion on the role of the chiral primary tertiary diamine salt in the catalysis of the aldol reactions is also presented.     

About the stereoselectivity control in reactions of chiral ortho-sulfinyl benzyl carbanions with aldehydes

Reactions of aliphatic and aromatic aldehydes with the benzyllithium derived from 2-p-tolylsulfinyl ethylbenzene yield mixtures of mainly two compounds, anti-3 and syn-4, epimers at hydroxylic carbon, easily separated by chromatography and desulfinylated into enantiomerically pure 1-alkyl (or aryl)-2-phenyl-1-propanols. The observed stereoselectivity at C(1) and C(2) is analyzed to the light of the steric and electronic effects of the substituents.     

Highly stereoselective direct aldol reactions catalyzed by (S)-NOBIN-l-prolinamide

(S)-NOBIN-l-prolinamide was employed as organocatalyst in the direct aldol reactions of different ketones and aromatic aldehydes using dioxane as solvent and in the presence of water as additive. Acetone led to the aldol products in up to 93% ee, while cyclic ketones furnished the anti-aldols in moderate to high yield, excellent diastereoselectivity (up to >99/<1 anti/syn ratio) and high ee (up to 95%).     

Isomerization of E-α,β-epoxyamides to Z-α,β-epoxyamides and synthetic applications based on regio- and stereoselective oxirane ring openings

The regioselective opening reaction of 2,3-epoxyamides with various nucleophiles offers a variety of β-hydroxyamides with diverse synthetic utility depending on the introduced nucleophile. Due to the exclusive stereoselectivity in the formation of trans epoxyamides in reactions of aldehydes with stabilized sulfur ylides, we studied the isomerization of trans epoxyamides into the cis isomers with the objective of obtaining the corresponding syn opening products, which together with the anti isomers represent a variety of enantiomerically pure building blocks.     

HClO4-SiO2 catalyzed stereoselective synthesis of β-amino ketones via a direct Mannich-type reaction

The HClO₄-SiO₂ catalyzed three-component, one-pot Mannich reaction of ketones, aromatic aldehydes and aromatic amines is carried out in ethanol to afford the corresponding β-amino ketones in good yields and high stereoselectivities in favor of the anti-isomer. Three new compounds are reported.     

Stereoselective titanium-mediated syn-aldol reaction from a lactate-derived chiral ethyl ketone

Stereoselectivity of the titanium-mediated aldol process based on (S)-2-benzyloxy-3-pentanone, 1, is dramatically modified by the presence of a Lewis acid. Among the Lewis acids surveyed, TiCl₄ has given access to the corresponding 2,4-anti-4,5-syn aldol adducts with the highest diastereomeric ratios. The excellent stereocontrol exerted by the aforementioned ketone has been demonstrated in double asymmetric reactions involving chiral α-methyl-β-OTBDPS aldehydes.     

Marked difference in singlet-chemiexcitation efficiency between syn-anti isomers of spiro[1,2-dioxetane-3,1′-dihydroisobenzofuran] for intramolecular charge-transfer-induced decomposition

Spiro[1,2-dioxetane-3,1′-dihydroisobenzofuran] syn-3 bearing a hydroxy group at the 6-position (as a model syn-rotamer of parent dioxetane 4 bearing a 3-hydroxyphenyl group) and its isomer anti-3 (as a model anti-rotamer of 4) were synthesized. When these spiro-dioxetanes were treated with tetrabutylammonium fluoride (TBAF) in DMSO, anti-3 emitted light with high efficiency (Φ^CL = 0.41), while the respective value for syn-3 was only 1/10 for anti-3. This significant difference in Φ^CL between syn-3 and anti-3 was attributed to the difference in their singlet-chemiexcitation efficiencies.     

Unexpected 1,2 syn diastereoselectivity in the three-component ‘aza Sakurai-Hosomi’ reaction

The three-component ‘aza Sakurai-Hosomi’ reaction performed on (±) O-protected mandelic aldehydes provided the unexpected syn hydroxy homoallylamines 2 and 2d as the major adducts. An intramolecular chelated transition state via a hydrogen bond is proposed to explain this 1,2 syn diastereoselectivity.     

Synthesis of novel thiol taxoids based on the 7,10-di-(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III: both the syn and anti 10-deacetyl-2′-deoxy-2′-mercaptopaclitaxels

Two new kinds of docetaxel compound, with a mercapto group instead of the hydroxyl on the C13 side chain (both syn and anti), via the 7,10-di-(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III route, were synthesized. The uses of trans and cis oxazoline compounds, and their stereoselective ring-opening reactions with thiolacetic acid, were proved to be key steps.     

Asymmetric synthesis of syn and anti methyl 2,3-diamino-3-phenylpropanoate derivatives from N-substituted imines and Schöllkopf's bislactim ether

The reaction between differently N-substituted benzaldimines and (2R)-Schöllkopf's bislactim ether was studied: the azaenolate addition to imines followed by hydrolysis of the resulting adducts gave syn-(2S,3R) and anti-(2S,3S)-methyl 2,3-diamino-3-phenylpropanoate derivatives in good yields. The configurations of the newly formed stereocenters of α,β-diamino acids were assigned on the basis of the ¹H NMR analysis and by comparison with known products. The diastereoisomeric ratios were explained taking into account the effect of the substituent present on the imine nitrogen on the transition state stability. This method represents a new approach for stereoselective synthesis of α,β-diamino acids.     

Anti-selective direct asymmetric Mannich reaction catalyzed by protease

The anti-selective direct asymmetric Mannich reaction of (hetero) aromatic aldehydes, 4-anisidine and O-protected hydroxyacetones for the synthesis of stereodefined anti-β-amino-α-hydroxycarbonyl compounds was developed. Protease type XIV from Streptomyces griseus (SGP) was used as a biocatalyst in 1,4-dioxane/phosphate buffer under mild reaction conditions. The excellent diastereoselectivities of up to >99:1 (anti/syn) and good enantioselectivities of up to 90% ee were achieved. This method provides a more sustainable complement to chemically catalyzed anti-selective direct asymmetric Mannich reactions.     

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.     

Remote substituent effect favoring the formation of syn-adducts in the chelation controlled radical reactions of γ-benzyloxy-α-methylenecarboxylic acid esters

The chelation controlled radical reactions of ethyl γ-benzyloxy-α-methylenecarboxylates bearing a bulky γ-substituent, such as CHMe₂, CHPh₂, c-C₆H₁₁ and CH(Ph)OTBDMS, with alkyl iodides gave the syn-adducts with high diastereoselectivities. However, the diastereoselectivity for the substrates bearing a γ-substituent CH(i-Pr)OTBDMS depended critically on the configuration of the substituent; the substrate bearing the OTBDMS group anti to the γ-benzyloxy group showed poor diastereoselectivity, but its diastereomer gave syn-adduct exclusively. The high syn-selectivitiy is referred to the H-atom transfer to the outside face of radical center in the sharply folded seven-membered chelate intermediate bearing the ethoxy group with Z-geometry. The corner flapping of the radical center atom of the global minimum energy conformer generates a local minimum conformer and the H-atom transfer to the outside face of the radical center of the newly formed structure gives the anti-adduct. The poor diastereoselectivity is due to the very small energy difference between the two conformers and consequently both the syn- and anti-adducts are yielded in nearly equal amounts.     

(S)-Threonine/α,α-(S)-diphenylvalinol-derived chiral ionic liquid: an immobilized organocatalyst for asymmetric syn-aldol reactions

Chiral ionic liquids containing (S)- or (R)-threonine amide and α,α-(S)-diphenylvalinol units were synthesized In the presence of the (S)-threonine-derived catalyst reactions between ketones with secondary carbon atom(s) at the α-position with respect to the carbonyl group and aromatic (heteroaromatic) aldehydes afforded the corresponding syn-aldols in high yields (up to 99%) and with high diastereo-(syn/anti up to 97:3) and enantioselectivity (up to 99% ee), which was maintained over three reaction cycles.     

Studies of some hydrogenated thiazolo[2,3-a]isoquinoline S-oxides

Several hydrogenated thiazolo[2,3-a]isoquinolinone S-oxides have been prepared and their stereochemistry established on the basis of spectral data analysis combined with X-ray crystallography. A reversible syn/anti isomerization of diastereomeric sulfoxides has been postulated to occur via a 10b proton abstraction.     

Crystal structures of anti- and syn-9,10-di(1′-naphthyl)anthracene and isomerization in solid state

9,10-Di-(1′-naphthyl)anthracene is often used as electroluminescence materials in organic light-emitting diodes. Because of the hindered rotation about the σ-bond between naphthyl and anthracene chromophore, two possible stereoisomers can be isolated. HPLC, ¹H NMR, and ¹³C NMR spectra gave two different sets of peaks and the X-ray single crystal analysis confirmed the structures of the two isomers, anti and syn. syn was more soluble than anti in THF as well as toluene and the thermal properties of the two were quite different. Differential scanning calorimetry study and HPLC analysis showed that the isomerization between anti and syn in the solid state took place at >370 °C.