l-Proline-catalyzed diastereoselective synthesis of cis-isoquinolonic acids and evaluation of their neuroprotective effects

l-Proline efficiently catalyzes the one-pot, three-component reaction of homophthalic anhydride, amines, and aldehydes in CH₃CN at room temperature, to afford the corresponding cis-isoquinolonic acids in high yields and with excellent diastereoselectivities. The synthesized compounds are screened for neuroprotective activities.     

Highly cis‐Diastereoselective Synthesis of Coumarin‐Based 2,3‐Disubstituted Dihydrobenzothiazines by Organocatalysis

An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin‐based dihydrobenzothiazoles was developed to afford cis‐2,3‐disubstituted 3,4‐dihydro‐2H‐benzothiazines. This method provides a one‐step and highly diastereoselective route to a wide variety of coumarin‐based 3,4‐dihydro‐2H‐benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.     

A diastereoselective Mannich reaction of α-fluoroketones with ketimines: Construction of β-fluoroamine motifs with vicinal tetrasubstituted stereocenters

A diastereoselective Mannich reaction has been developed for the synthesis of chiral β-fluoroamine motifs by the reaction of α-fluoroketones with ketimines, including isatin-derived ketimines and phenylglyoxylate-derived ketimines. This method provides a concise route to a variety of biologically important 3-aminooxindoles and α-amino acids featuring fluorine-containing vicinal tetrasubstituted stereocenters.     

Trimethylaluminium-induced diastereoselective methylation onto ethyl 2-oxocyclopentane-1-carboxylate and isomerization between the dimethylaluminium-alkoxide products

Methylation of α-disubstituted cyclopentanone 1 with Me₃Al in CH₂Cl₂ at 0 °C for 30 min gave diastereoselectively a mixture of (1R*,2S*)-2 and (1R*,2R*)-2 in a 96:4 ratio and 83% total yield. When the same methylation was carried out at 0 °C for 1 h and then at room temperature for 120 h, a diastereomeric mixture of (1R*,2S*)-2 and (1R*,2R*)-2 was obtained in a 12:88 ratio and in 88% total yield. The stereochemistry of the two diastereomers was determined by the results of acetalization of their diol derivatives 3 and 5. Isomerization between the Me₂Al-alkoxides of (1R*,2S*)-2 and (1R*,2R*)-2 and its possible mechanism were investigated by HPLC analysis of the methylation reaction process at 0 °C for 1 h and then at room temperature for 56 h and also by their mutual epimerization reactions.     

Stereoselective synthesis of activated cyclopropanes with an α-pyridinium acetamide bearing an 8-phenylmenthyl group as the chiral auxiliary

The reaction between an α-pyridinium acetamide bearing an 8-phenylmenthyl group as the chiral auxiliary and β-substituted methylidenemalononitriles gave rise to trans-cyclopropanes with diastereomeric ratios of up to 98:2. For most of the reactions, the absolute stereochemistry of the major product was found to be opposite of that of the major products of the reaction of the corresponding ester series, which also utilized the 8-phenylmenthyl group.     

Synthesis of (2S,7S)-dibutyroxynonane, the sex pheromone of the orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), by diastereoselective silicon-tethered ring-closing metathesis

The sex pheromone of Sitodiplosis mosellana, (2S,7S)-dibutyroxynonane, has been synthesised using a mixed di-t-butylsilaketal prepared from (S)-5-hexen-2-ol and prochiral 1,4-pentadiene-3-ol. Ring-closing metathesis occurs diastereoselectively and after the removal of the silyl group and the reduction of the double bonds, generates (2S,7S)-nonanediol with a diastereoisomeric excess of 94% as measured by gas chromatographic analysis of the diacetylated product.     

One-pot three-component reaction of fluoroalkanesulfonyl azide, vinyl ether and aldehyde: the formation of polysubstituted fluorinated oxazolidines

Efficient and diastereoselective synthesis of highly substituted fluorinated oxazolidines was achieved via a one-pot three-component reaction of fluoroalkanesulfonyl azides 1, vinyl ether 2 and various aldehydes at 0 °C within 10 min in moderate to good diastereoselectivities (syn/anti). A competing process could be involved in the initial step and an unstable fluorinated aziridine was postulated as the intermediate for these reactions. Additionally, rational transition states were also proposed to elucidate the diastereoselectivities. This synthetic method provides a convenient and expeditious access to N-per(poly)fluoroalkanesulfonyl oxazolidines.     

Diastereoselective Baylis-Hillman reaction: first use of chiral 2,3-epoxy aldehydes as novel electrophiles

Chiral 2,3-epoxy aldehydes have been effectively utilized for the first time as novel electrophiles in Baylis-Hillman reactions with activated alkenes to result in densely functionalized adducts in good yields (61-80%) and in moderate to good diastereoselectivities (40-72% de).     

Reduction of substituted 1,10-phenanthrolines as a route to rigid chiral benzimidazolylidenes

Variously substituted 1,10-phenanthrolines are reduced to octahydrophenanthrolines in moderate to good yields with NaBH₃CN in acetic acid/methanol. The exact solvent composition is important to avoid the formation of tetrahydrophenanthrolines and N-alkylated byproducts, and to optimize the formation of octahydrophenanthrolines. Resolution of a racemic reduction product gives an enantiomerically pure C₂-symmetric diamine from which the corresponding rigid benzimidazolylidene is prepared, whereas reduction of chiral phenanthrolines derived from bicyclic ketones affords diastereomerically pure diamines, which may also be converted to benzimidazolylidenes.     

Highly diastereoselective cycloaddition reactions of variously substituted 1-thia- and 1-thia-3-aza-buta-1,3-dienes. Synthesis of enantiomerically pure 5,6-dihydro-4H-[1,3]thiazines and 3,4-dihydro-2H-thiopyrans

The cycloaddition of 2- or 2,3-substituted 1-thia- and 1-thia-3-aza-4-dimethylamino-buta-1,3-dienes with various dienophiles in the presence of a Lewis acid provides a rapid and diastereoselective access to the 3,4-dihydro-2H-thiopyran and 5,6-dihydro-4H-[1,3]thiazine backbones. The generally observed trans relationship between the two newly created strereogenic centres was demonstrated to be the expression of a thermodynamic control of the reaction. The use of chiral dienophile derived from chiral oxazolidin-2-ones allowed us to prepare enantiopure 5,6-dihydro-4H-[1,3]thiazines and 3,4-dihydro-2H-thiopyrans. In the asymmetric synthetic process the chiral auxiliary removal step was best accomplished in the presence of samarium triflate in methanol.