A general synthesis of iminosugars

1-Deoxynojirimycin, 1-deoxymannojirimycin, and 1-deoxygalactostatin have been synthesized by epoxidation of tri-O-acetyl-6-deoxyhex-5-enopyranosyl azides followed by methanolysis, deacetylation, and catalytic hydrogenation. 1,6-Dideoxygalactostatin was obtained by the reaction of 2,3,4-tri-O-acetyl-6-deoxy-beta-L-arabino-hex-5-enopyranosyl azide with NIS in methanol followed by deacetylation and catalytic hydrogenation. The overall yields were 4.4-23.5% over seven to nine steps.     

Stereoselective synthesis of enantiopure N-protected-3-arylpiperazines from keto-esters

An efficient method for a stereoselective synthesis of optically pure N-Boc-3-arylpiperazines has been developed. After optimization of the protecting group strategy and experimental conditions, compounds were obtained via a highly stereoselective synthesis in up to 45% overall yield. This is a practical route to optically pure piperazines for medicinal chemistry.     

Stereoselective synthesis of 3-heteroaromatic-substituted alanines

An asymmetric synthesis of (R)-3-heterocyclic-substituted alanines starting from (2S)-(+)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (Schöllkopf reagent) and heteroaromatic halogenomethyl derivatives via hydrolysis of intermediate adducts is reported. The diastereocontrolled addition gives mainly compounds with the (2S,5R) configuration whose formation is explained on the basis of the accepted model for the alkylation reaction of the Schöllkopf reagent, and structure confirmed by spectroscopic data.     

Stereoselective synthesis of erythro-3-fluorophenylalanine

Reductive amination of 3-fluorophenylpyruvic acid was found to give erythro-3-fluorophenylalanine with high selectivity.     

Stereoselective synthesis of 3-oxygenated-cis-dialkyl-2,5-substituted tetrahydrofurans from cyclohexadienediols

The 3-oxygenated-cis-dialkyl-2,5-substituted tetrahydrofuran system, present in several natural products, was prepared with good selectivity by acidic cyclization of 5-alkene-1,2,4-triol derivatives. The starting alkenol was obtained in few steps from a chiral cis-diol resulting from microbial oxidation of bromobenzene. The study of the cyclization allowed the rationalization of all experimental results by assuming a complete ionization at the allylic position and a model close to the one proposed by Labelle for homoallylic induction in five-membered ring closures.     

Stereoselective synthesis of tetrahydrofuran-3-carbaldehyde

Trans-tetrahydrofuran-3-carbaldehydes are prepared by ruthenium-catalyzed isomerization of 4,7-dihydro-1,3-dioxepines and subsequent Lewis acid-catalyzed 1,3-alkyl migration.     

Stereoselective synthesis of N-alkylaziridines from N-chloroamines

We report the first racemic and stereoselective synthesis of cis- and trans-N-alkylaziridines viaN-chloroamines; using this methodology an N-3,4,5-trimethoxybenzylaziridine was synthesised and efficiently cleaved, affording the corresponding NH aziridine in high yield.     

Stereoselective synthesis of swainsonines from pyridines

An efficient synthesis of (−)-swainsonine and (−)-2,8a-di-epi-swainsonine was developed starting from readily available 2-pyridinecarbaldehyde and 3-hydroxypyridine. In particular, it was demonstrated that the mixture of simple indolizidines, i.e. lentiginosine and epi-lentiginosine, being readily available by a number of different synthetic routes, can be directly converted to swainsonine.     

Stereoselective synthesis of allylsilanes from chloromethylsilylalkynes

Regio- and stereoselective hydralumination of 1-chloromethyldimethylsilyl-1-alkyne with DIBAH affords (Z)-1- chloromethyldimethylsilyl-1-diisobutylalumino-1-alkene which gives (E)-1-trimethylsilyl-2-alkene as a sole product by successive treatment with 3 equiv of methyllithium and water. Reaction of the organoaluminium intermediate with trimethyl-aluminium in refluxing heptane produces a mixture of (Z)- and (E)-1-trimethylsilyl-2-alkene.     

Stereoselective synthesis of chiral 3-aryl-1-alkynes from bromoallenes and heterocuprates

The synthesis of chiral 3-aryl-1-alkynes 3 via cross-coupling of 3-alkyl- and 3,3-dialkyl-1-bromo-1,2-dienes 1 and arylbromocuprates (RCuBr)MgBr.LiBr 2 was examined. With phenylcopper reagents and its para-substituted derivatives, as well as with 2-naphthyl cuprates, the reaction gave compounds 3 with high regioselectivity and good yields on the chemically pure product. On the contrary, when ortho-substituted phenyl reagents and 1-naphthyl cuprates were used, the regioselectivity of the process was very dependent upon the steric requirements of the alkyl substituents on the bromoallenic substrate. When the steric bulk was increased, remarkable quantities of isomeric arylallenes 4 were also observed in the reaction mixtures. The high 1,3-anti stereoselectivity of the coupling process allowed us to obtain enantiomerically enriched 3-aryl-1-alkynes from optically active allenic substrates, thus indicating a simple pathway toward the synthesis of quaternary stereogenic centers characterized by an aryl group. A possible cross-coupling mechanism was also suggested to explain the regio- and stereochemical data. For the preparation of omega-functionalized 3-phenyl-1-alkynes, the reaction of 1-bromo-3-phenylpropadiene with Knochel reagents RCu(CN)ZnCl.2LiCl was also studied; this reaction led to the acetylenic compounds in high yields mainly when the R group (also omega-functionalized) on the copper reagent was primary.     

Stereoselective synthesis of (+)-cerulenin from d-glucose

(+)-Cerulenin $\text{1a}$ was synthesized stereoselectively from D-glucose.     

Stereoselective synthesis of protected 3-amino-3,6-dideoxyaminosugars

New syntheses of densely functionalized protected derivatives of 3-amino-3,6-dideoxyaminosugars have been accomplished in an efficient and straightforward manner. The key step of such approaches involves a highly stereoselective titanium-mediated aldol addition of a chiral α-bromo ketone, easily available from lactate esters, to crotonaldehyde. Further functional group transformations, including a new regioselective Staudinger-aza-Wittig reaction of an azidodiacetate, afford in a few steps and high yield the desired carbohydrates as advanced intermediates capable of participating in subsequent glycosylation reactions.     

Stereoselective synthesis of 3-alkylidene/alkylazetidin-2-ones from azetidin-2,3-diones

Azetidin-2,3-diones have been used as synthons for the synthesis of C-3 alkylidene/alkylazetidin-2-ones. Some of the 3-alkylazetidin-2-ones are well known for their cholesterol absorption inhibitor activity. A regio and stereoselective Grignard reaction on a keto group followed by dehydration using PPh₃/CCl₄ reagent is a key step in this synthesis. Hydrogenation of the 3-alkylideneazetidin-2-ones provided stereoselectively cis-3-alkylazetidin-2-ones in very good yields.     

Stereoselective synthesis of 3-hydroxyproline benzyl esters from N-protected beta-aminoaldehydes and benzyl diazoacetate

The synthesis of a series of 3-hydroxyproline benzyl esters from alpha-alkyl and alpha-alkoxy N-protected aminoaldehydes with benzyl diazoacetate is described. Aldehydes with alpha-alkyl substituents afforded prolines as a single diastereomer with a trans-cis relative configuration in 14-77%. An alpha-tert-butyldimethylsilyloxy aminoaldehyde afforded a proline as a single diastereomer with a trans-trans relative configuration in 37% yield.     

Stereoselective synthesis of azetidine-derived glutamate and aspartate analogues from chiral azetidin-3-ones

The stereoselective syntheses of cis conformationally constrained glutamate and aspartate analogues, containing an azetidine framework were accomplished from (S)-N-tosyl-2-phenylglycine in moderate overall yields. The key steps in these syntheses involved an efficient Wittig olefination of an azetidin-3-one, followed by a highly stereoselective rhodium catalyzed hydrogenation. The route could also be applied to the synthesis of a trans glutamate analogue, since epimerization of cis to trans isomer could be performed using DBU in toluene at reflux.     

Stereoselective synthesis of 3-substituted tetrahydroisoquinolines from phthalan and chiral N-sulfinylimines

The reaction of the dianionic intermediate [resulting from the reductive opening of phthalan (1) with lithium] with chiral N-tert-butylsulfinyl aldimines 3 in the presence of ZnMe₂ gives, after hydrolysis, N-tert-butylsulfinyl amino alcohols 4 with high diastereoselectivity. Successive treatment of compounds 4 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide yields 3-substituted tetrahydroisoquinolines 6.     

A rapid synthesis of hexofuranose-like iminosugars using ring-closing metathesis

Two new 1-N-iminosugars have been prepared as hexofuranose analogues in an efficient manner by an RCM-based route. Both 3,4-disubstituted pyrrolidines display moderate inhibitory activity against Mycobacterium smegmatis galactan biosynthesis. [structure: see text]     

Stereoselective synthesis of 3-alkylideneoxindoles via palladium-catalyzed domino reactions

We have developed efficient catalytic methods for the stereoselective and diversity synthesis of various (E)-, (Z)-, and disubstituted 3-alkylideneoxindoles and 3-alkylidenebenzofuran-2-ones via palladium-catalyzed Heck/Suzuki-Miyaura, Heck/Heck, and Heck/carbonylation/Suzuki-Miyaura domino reactions.