A ring-closing metathesis route to 7-membered aza-heteroannulated sugars

Azepane rings have been constructed diastereoselectively upon a carbohydrate derivative utilising reductive amination and RCM. The stereochemistry of the ring junctions was confirmed by X-ray crystallography and NMR. Diastereoselective dihydroxylation has also been employed to afford a tetrahydroxylated azepane carbohydrate derivative with potential biological activity.     

Pd-catalyzed one-pot coupling of allylamines, activated alkenes, and unsaturated halides (or triflate): an atom efficient synthesis of highly functionalized pyrrolidines

A Pd-catalyzed three-component assembling of highly functionalized 4-benzyl-(and allyl-)pyrrolidines was achieved based on a combination of allyl amines, gem-diactivated alkenes, and unsaturated halides (or triflate).     

Synthesis of pyrrolidine-substituted benzamides via iodocyclization of β-enaminoesters

Novel 2-, and N-substituted 5-methylene-pyrrolidine benzamides and 2-, 3-, and N-substituted 5-methylene-2-pyrroline benzamides were synthesized for the first time in a straightforward manner and in good yields via iodocyclization of γ- and α-alkenyl-β-enaminoesters, respectively. The key step in the process is the synthesis of the methylene-pyrrolidine iodide and methylene-2-pyrroline iodide intermediates. Functional group inter-conversion of these iodides to their amino analogs, and their subsequent coupling to benzoic acids via EDC, afforded the above pyrrolidine/2-pyrroline-substituted benzamides in yields of around 75%.     

1,3-Dipolar cycloaddition approach to pyrrolidine analogues of C-nucleosides related to pseudouridine

Pyrrolidine analogues of C-nucleosides related to pseudouridine have been synthesized by 1,3-dipolar cycloaddition reactions of uracil-5 and 2,4-dimethoxypyrimidine-5 nitrones with allyl alcohol and methyl acrylate, and subsequent reductive cleavage of the isoxazolidine cycloadducts. The dimethoxy derivatives have been easily deprotected to the corresponding uracils bearing the pyrrolidine ring instead of a sugar moiety. The regio and stereoselectivity of the reactions are discussed.     

γ-Lactam-containing peptidomimetics

Protected diaminoalcohols obtained through allyl addition to α-amino acid-derived imines and subsequent hydroboration were used for the preparation of pyrrolidinones and pyrrolidines. Pyrrolidinones were synthesized with moderate yields by oxidation of the hydroxy function with tetrapropylammonium perruthenate/N-methylmorpholine-N-oxide and concomitant cyclization while pyrrolidines were synthesized in good yields by tosylation of the hydroxy group and subsequent intramolecular nucleophilic substitution. Thus accessible substrates were transferred into peptidomimetics by attachment of amino acid moieties at both termini using conventional peptide coupling strategies. Molecular mechanics optimizations suggest that these substrates preferentially adopt a turn conformation.     

CCC-N-heterocyclic carbene pincer complexes: Synthesis, characterization and hydroamination activity of a hafnium complex

Our methodology for the stoichiometric preparation of CCC-NHC pincer complexes of Zr has been extended to Hf. The CCC^Bu-NHC pincer Hf complex has been characterized by X-ray crystal structure analysis. Catalytic activity in the intramolecular hydroamination/cyclization of unactivated alkenes is reported and compared to the recently reported Zr analog. An improved, scaled-up CuO-catalyzed aryl amination of 1,3-dibromobenzene and an improved salt formation methodology for preparation of bis(butyl-imidazolium)benzene are reported also.     

Synthesis of 3‐Acyl‐4‐alkenylpyrrolidines by Platinum‐Catalyzed Hydrative Cyclization of Allenynes

A series of nitrogen‐tethered allenynes (‘5‐aza‐1,2‐dien‐7‐ynes’) 1 were transformed to the corresponding 3‐acyl‐4‐alkenylpyrrolidines 3 when treated with a catalytic amount of PtCl₂ in MeOH at 70°. Initial Pt‐promoted cyclization forms a nonclassical carbocationic intermediate. In contrast to the cycloisomerization in toluene, which produced the bicyclic cyclobutenes 2 , the intermediate is intercepted by addition of an oxygen nucleophile to achieve the formal hydrative cyclization.     

Nonstabilized azomethine ylides in the synthesis of aryl cucurbitine derivatives

Nonstabilized azomethine ylides react with 4-arylidene-2-phenyloxazol-5(4H)-ones to form diazaspiro[4.4]nonenes, which were hydrolyzed to aryl cucurbitine derivatives in 35–67% overall yield.     

A highly stereocontrolled route to 2-(2′-oxiranyl)piperidines and pyrrolidines: enantioselective synthesis of (+)-α-conhydrine

The first enantio- and diastereoselective approach to both 2-(2′-oxiranyl)piperidines and to 2-(2′-oxiranyl)pyrrolidines is reported. The method relies on the Sharpless asymmetric epoxidation of allyl alcohols as the sole source of chirality, and involves as the key step the base-mediated cyclization of (α-aminoalkyl)oxiranes functionalized at the ? (or δ) position. The asymmetric synthesis of (+)-α-conhydrine illustrates the applicability of this strategy to the preparation of biologically active 2-(1-hydroxyalkyl)piperidine alkaloids.     

First Total Synthesis of Hyacinthacine A6 from the Protected Derivative of Polyhydroxylated Pyrrolidine

（1S、2R、3R、5R、7aR）-1,2-Dihydroxy-3-hydroxy methyl-5-methylpyrrolizidine（hyacinthacine A6, I） was synthesized by Wittig＇s methodology via the reaction of aldehyde 6, prepared from the partially protected derivative of polyhydroxylated pyrrolidine, with appropriated ylides, followed by cyclization through the intemal reductive amination process of the resulting a,B-unsaturated ketone 7, and total deprotection.